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Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis
Morrison, Charles S.
Chen, Pai-Lien
Kwok, Cynthia
Baeten, Jared M.
Brown, Joelle
Crook, Angela M.
Van Damme, Lut
Delany-Moretlwe, Sinead
Francis, Suzanna C.
Friedland, Barbara A.
Hayes, Richard J.
Heffron, Renee
Kapiga, Saidi
Karim, Quarraisha Abdool
Karpoff, Stephanie
Kaul, Rupert
McClelland, R. Scott
McCormack, Sheena
McGrath, Nuala
Myer, Landon
Rees, Helen
van der Straten, Ariane
Watson-Jones, Deborah
van de Wijgert, Janneke H. H. M.
Stalter, Randy
Low, Nicola
PLoS Medicine
In a meta-analysis of individual participant data, Charles Morrison and colleagues explore the association between hormonal contraception use and risk of HIV infection in sub-Saharan Africa.
Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC.
Methods and Findings
Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15–49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37,124 women (43,613 woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24–1.83) for DMPA use, 1.24 (95% CI 0.84–1.82) for NET-EN use, and 1.03 (95% CI 0.88–1.20) for COC use. Between-study heterogeneity was mild (I2 < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23–1.67) and NET-EN use (aHR 1.32, 95% CI 1.08–1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99–1.50; for NET-EN use 0.67, 95% CI 0.47–0.96; and for COC use 0.91, 95% CI 0.73–1.41) compared to those at higher risk of bias (pinteraction = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC–HIV relationship.
This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.
Editors' Summary
AIDS has killed about 36 million people since the first recorded case of the disease in 1981. About 35 million people (including 25 million living in sub-Saharan Africa) are currently infected with HIV, the virus that causes AIDS, and every year, another 2.3 million people become newly infected with HIV. At the beginning of the epidemic, more men than women were infected with HIV. Now, about half of all adults infected with HIV are women. In 2013, almost 60% of all new HIV infections among young people aged 15–24 years occurred among women, and it is estimated that, worldwide, 50 young women are newly infected with HIV every hour. Most women become infected with HIV through unprotected intercourse with an infected male partner—biologically, women are twice as likely to become infected through unprotected intercourse as men. A woman's risk of becoming infected with HIV can be reduced by abstaining from sex, by having one or a few partners, and by always using condoms.
Why Was This Study Done?
Women and societies both benefit from effective contraception. When contraception is available, women can avoid unintended pregnancies, fewer women and babies die during pregnancy and childbirth, and maternal and infant health improves. However, some (but not all) observational studies (investigations that measure associations between the characteristics of participants and their subsequent development of specific diseases) have reported an association between hormonal contraceptive use and an increased risk of HIV acquisition by women. So, does hormonal contraception increase the risk of HIV acquisition among women or not? Here, to investigate this question, the researchers undertake an individual participant data meta-analysis of studies conducted in sub-Saharan Africa (a region where both HIV infection and unintended pregnancies are common) to compare the incidence of HIV infection (the number of new cases in a population during a given time period) among women using and not using hormonal contraception. Meta-analysis is a statistical method that combines the results of several studies; an individual participant data meta-analysis combines the data recorded for each individual involved in the studies rather than the aggregated results from each study.
What Did the Researchers Do and Find?
The researchers included 18 studies that measured hormonal contraceptive use and incident HIV infection among women aged 15–49 years living in sub-Saharan Africa in their meta-analysis. More than 37,000 women took part in these studies, and 1,830 became newly infected with HIV. Half of the women were not using hormonal contraception, a quarter were using depot-medroxyprogesterone acetate (DMPA; an injectable hormonal contraceptive), and the remainder were using combined oral contraceptives (COCs) or norethisterone enanthate (NET-EN, another injectable contraceptive). After adjustment for other factors likely to influence HIV acquisition (for example, condom use), women using DMPA had a 1.5-fold increased risk of HIV acquisition compared to women not using hormonal contraception. There was a slightly increased risk of HIV acquisition among women using NET-EN compared to women not using hormonal contraception, but this increase was not statistically significant (it may have happened by chance alone). There was no increased risk of HIV acquisition associated with COC use. DMPA use was associated with a 1.43-fold and 1.32-fold increased risk of HIV acquisition compared with COC and NET-EN use, respectively. Finally, neither age nor herpes simplex virus 2 infection status modified the effect of hormonal contraceptive use on HIV acquisition.
What Do These Findings Mean?
The findings of this individual patient data meta-analysis provide no evidence that COC or NET-EN use increases a woman's risk of acquiring HIV, but add to the evidence suggesting that DMPA use increases the risk of HIV acquisition. These findings are likely to be more accurate than those of previous meta-analyses that used aggregated data but are likely to be limited by the quality, design, and representativeness of the studies included in the analysis. These findings nevertheless highlight the need to develop additional safe and effective contraceptive options for women at risk of HIV, particularly those living in sub-Saharan Africa, where although contraceptive use is generally low, DMPA is the most widely used hormonal contraceptive. In addition, these findings highlight the need to initiate randomized controlled trials to provide more definitive evidence of the effects of hormonal contraception, particularly DMPA, on HIV risk.
Additional Information.
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001778.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment, including personal stories about living with HIV/AIDS and a news report on this meta-analysis
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including detailed information on women, HIV, and AIDS, and on HIV and AIDS in South Africa (in English and Spanish); personal stories of women living with HIV are available
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages); information about a 2012 WHO technical consultation about hormonal contraception and HIV
The 2013 UNAIDS World AIDS Day report provides up-to-date information about the AIDS epidemic and efforts to halt it; UNAIDS also provides information about HIV and hormonal contraception
Related Articles
Progestin-only contraceptives: effects on weight
Lopez, Laureen M
Edelman, Alison
Chen, Mario
Otterness, Conrad
Trussell, James
Helmerhorst, Frans M
The Cochrane database of systematic reviews
Progestin-only contraceptives (POCs) are appropriate for many women who cannot or should not take estrogen. Many POCs are long-acting, cost-effective methods of preventing pregnancy. However, concern about weight gain can deter the initiation of contraceptives and cause early discontinuation among users.
The primary objective was to evaluate the association between progestin-only contraceptive use and changes in body weight.
Search methods
Through May 2013, we searched MEDLINE, CENTRAL, POPLINE, LILACS, ClinicalTrials.gov, and ICTRP. The 2010 search also included EMBASE. For the initial review, we contacted investigators to identify other trials.
Selection criteria
All comparative studies were eligible that examined a POC versus another contraceptive method or no contraceptive. The primary outcome was mean change in body weight or mean change in body composition. We also considered the dichotomous outcome of loss or gain of a specified amount of weight.
Data collection and analysis
Two authors extracted the data. We computed the mean difference (MD) with 95% confidence interval (CI) for continuous variables. For dichotomous outcomes, the Mantel-Haenszel odds ratio (OR) with 95% CI was calculated.
Main results
We found 16 studies; one examined progestin-only pills, one studied the levonorgestrel-releasing intrauterine system (LNG-IUS), four examined an implant, and 10 focused on depot medroxyprogesterone acetate (DMPA). Outcomes examined were changes in body weight only (14 studies), changes in both body weight and body composition (1 study), and changes in body composition only (1 study). We did not conduct meta-analysis due to the various contraceptive methods and weight change measures.
Comparison groups did not differ significantly for weight change in 12 studies. However, three studies showed weight change differences for POC users compared to women not using a hormonal method. In one study, weight gain (kg) was greater for the DMPA group than the group using a non-hormonal IUD in years one through three [(MD 2.28; 95% CI 1.79 to 2.77), (MD 2.71, 95% CI 2.12 to 3.30), and (MD 3.17; 95% CI 2.51 to 3.83), respectively]. The differences were notable within the normal weight and overweight subgroups. Two implant studies also showed differences in weight change. The implant group (six-capsule) had greater weight gain (kg) compared to the group using a non-hormonal IUD in both studies [(MD 0.47 (95% CI 0.29 to 0.65); (MD 1.10; 95% CI 0.36 to 1.84)]. In one of those studies, the implant group also had greater weight gain than a group using a barrier method or no contraceptive (MD 0.74; 95% CI 0.52 to 0.96).
The two studies that assessed body composition change showed differences between POC users and women not using a hormonal method. Adolescents using DMPA had a greater increase in body fat (%) compared to a group not using a hormonal method (MD 11.00; 95% CI 2.64 to 19.36). The DMPA group also had a greater decrease in lean body mass (%) (MD −4.00; 95% CI −6.93 to −1.07). The other study reported differences between an LNG-IUS group and a non-hormonal IUD group in percent change in body fat mass (2.5% versus −1.3%, respectively; reported P value = 0.029) and percent change in lean body mass (−1.4% versus 1.0%, respectively; reported P value = 0.027).
Authors' conclusions
The overall quality of evidence was moderate to low, given that the studies were evenly divided across the evidence quality groups (high, moderate, low, or very low quality). We found limited evidence of weight gain when using POCs. Mean gain was less than 2 kg for most studies up to 12 months. Weight change for the POC group generally did not differ significantly from that of the comparison group using another contraceptive. Two studies that assessed body composition showed that POC users had greater increases in body fat and decreases in lean body mass compared to users of non-hormonal methods. Appropriate counseling about typical weight gain may help reduce discontinuation of contraceptives due to perceptions of weight gain.
Related Articles
Benefits and risks of hormonal contraception for women
Gorenoi, Vitali
Schönermark, Matthias P.
Hagen, Anja
GMS Health Technology Assessment
Scientific background
A large proportion of women of reproductive age in Germany use various methods of pregnancy prevention (contraception), among them various hormone-based methods. Hormonal contraceptives may be divided into combined estrogen-progestogen contraceptives (pills, skin patches, vaginal rings), progestogen-only contraceptives (pills, injections, implants, hormone spirals) and emergency contraceptives.
Research questions
The evaluation addressed the question of benefits and risks of hormonal contraceptives, their economic effects as well as their ethical-social and legal implications.
A systematic literature search was conducted in April 2006 starting from 2000. The evaluation is primarily based on systematic reviews.
In perfect use, all hormonal contraceptives excluding emergency contraceptives proved to be the most effective reversible contraceptive methods (rate of unintended pregnancies 0.05% to 0.3%). However, the typical use of oral contraceptives, injections, skin patches, and vaginal rings, which also considers possible application errors, showed a lower contraceptive efficacy (rate of unintended pregnancies 3% to 8%). It was lower than that of copper spirals.
The risk of venous thromboembolism increased three to six times in users of hormonal contraceptives, the risks of stroke and myocardial infarction two to three times. The risk declined after discontinuation of use. The effects were estrogen-dose and progestogen-type dependent.
The use of hormonal contraceptives showed a relative risk of ovarian and endometrial carcinomas of approximately 0.5 or 0.7, of breast and cervical cancer of approximately 1.2 or 1.6. The effect remained several years after discontinuation of use. The results concerning hepatocellular carcinoma suggested a carcinogenic effect.
In women with acne, an improvement due to use of hormonal contraceptives was proven. Cervical chlamydial infections were more frequent in users of hormonal contraception. Headache appeared mostly only at the beginning of the use of combined oral contraceptives. Progestogen-only contraceptives worsened the results of the glucose tolerance test. A review of low evidence reported further risks of hormonal contraceptives (concerning menstrual problems, ovarian cysts, bone density, thyroid diseases and rheumatoid arthritis) as well as further benefits (concerning blood pressure and Crohn's disease).
Hormonal spirals were shown to be more effective than spirals which do not release hormones. In emergency contraception, Levonorgestrel was more effective than the Yuzpe method. Most other proven differences between hormonal contraceptives were related to menstrual problems.
After spirals with or without hormone release, the other hormonal contraceptives were shown in typical use to be the second most cost-effective reversible methods of contraception.
The addressed questions could be answered only on relatively low evidence level, partly only for applications with estrogen doses which are not used in Germany any more. The transferability of the results of the analysed primary health-economics studies on the current situation in Germany is limited (clinical assumptions from out-dated information sources of low evidence levels, cost assumptions from the American health system).
In perfect use, hormonal contraceptives have to be classified as the most effective reversible contraceptive methods. For the individual decision concerning the use of hormonal contraception, benefits should be related to the additional risks. Alternative methods such as spirals should be prioritised if perfect use seems to be impossible. In this case, spirals are also preferable from health-economics perspective. No ethical-social or legal conclusions can be derived from the available data.
Related Articles
Efavirenz- but not nevirapine-based antiretroviral therapy decreases exposure to the levonorgestrel released from a sub-dermal contraceptive implant
Scarsi, Kimberly
Lamorde, Mohammed
Darin, Kristin
Dilly Penchala, Sujan
Else, Laura
Nakalema, Shadia
Byakika-Kibwika, Pauline
Khoo, Saye
Cohn, Susan
Merry, Concepta
Back, David
Journal of the International AIDS Society
2014;17(4Suppl 3):19484.
Sub-dermal hormone implants, such as levonorgestrel (LNG), are a safe and desirable form of long-acting contraception, but their use among HIV-positive women on antiretroviral therapy (ART) may be compromised given the potential for a cytochrome P450 3A-mediated drug–drug interaction. Our study aimed to characterize the pharmacokinetics of LNG released from a sub-dermal implant over six months in HIV-positive Ugandan women on nevirapine (NVP)- or efavirenz (EFV)-based ART.
Material and Methods
This non-randomized, parallel group study compared LNG pharmacokinetics between HIV-positive Ugandan women not yet eligible for ART (control group, n=18) and those on stable NVP- (n=20) or EFV- (n=20) based ART. The two-rod (75 mg/rod) LNG sub-dermal implant was inserted at study enrolment. LNG sampling was obtained pre-implant and at weeks 1, 4, 12 and 24 post-insertion. LNG concentrations were analyzed using a validated LC-MS/MS method, with an assay calibration range of 50–1500 pg/mL. Safety monitoring, including a pregnancy test, was conducted at each study visit.
At enrolment, participants had a mean age of 31 years; CD4+ cell counts were similar between the control, NVP and EFV groups (758, 645 and 568 cells/mm3, respectively; p=0.09); all women in the NVP and EFV groups had an undetectable HIV-RNA. Women in the control group had a higher baseline body weight (73 kg) compared to those in the NVP (63 kg; p=0.03) or EFV groups (60 kg; p<0.01). By linear regression, weight was a significant predictor of LNG concentrations (1 kg increase in weight=5 pg/mL decrease in LNG, p=0.03). LNG concentrations are reported in the table.
Over a 24-week period, LNG concentrations were 40–54% lower in women on EFV-based ART, despite their having a significantly lower body weight, compared to those not on ART. In women on NVP-based ART, LNG concentrations were 32–39% higher than those observed in the control group, a difference partially explained by body weight. These data confirm a significant drug interaction occurs between the LNG implant and EFV, adding to growing concern for reduced contraceptive efficacy with their combined use. In contrast, these data support use of the LNG implant with NVP-based ART.
Related Articles
PrEP is Efficacious for HIV-1 prevention among Women using DMPA for Contraception
HEFFRON, Renee
MUGO, Nelly
WERE, Edwin
KIARIE, James
BUKUSI, Elizabeth A.
MUJUGIRA, Andrew
FRENKEL, Lisa
DONNELL, Deborah
RONALD, Allan
CELUM, Connie
BAETEN, Jared M.
AIDS (London, England)
To evaluate pre-exposure prophylaxis (PrEP) efficacy for HIV-1 prevention among women using depot medroxyprogesterone acetate (DMPA) for contraception and men whose HIV-1 infected partners use DMPA.
Secondary analysis of data from a randomized placebo-controlled trial of daily oral tenofovir and emtricitabine/tenofovir PrEP among heterosexual Kenyan and Ugandan HIV-1 serodiscordant couples
PrEP efficacy for HIV-1 prevention was compared among HIV-1 uninfected women using DMPA versus no hormonal contraception and among HIV-1 uninfected men whose HIV-1 infected female partners used DMPA versus no hormonal contraception.
Of 4747 HIV-1 serodiscordant couples, 901 HIV-1 uninfected women used DMPA at some point during follow-up, 1422 HIV-1 uninfected women used no hormonal contraception, 1568 HIV-1 uninfected men had female partners who used DMPA, and 2626 men had female partners who used no hormonal contraception. PrEP efficacy estimates for HIV-1 prevention, compared to placebo, were similar among women using DMPA and those using no hormonal contraception (64.7% and 75.5%, adjusted interaction p=0.65). Similarly, for men whose female partners used DMPA, PrEP efficacy did not differ from men whose partners used no hormonal contraception (90.0% versus 81.7%, adjusted interaction p=0.52).
PrEP is efficacious for HIV-1 prevention among women using DMPA and men whose partners use DMPA, suggesting PrEP could mitigate the potential increased HIV-1 acquisition and transmission risks that have been associated with DMPA use. Women at risk for HIV-1 choosing DMPA could maintain this contraceptive method and add PrEP to achieve prevention of unintended pregnancy and HIV-1.
HIV-1 prevention; pre-exposure prophylaxis efficacy; hormonal contraception; DMPA
Related Articles
Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives
Benagiano, Giuseppe
Carrara, Sabina
Filippi, Valentina
Patient preference and adherence
The progestational steroid norgestrel was synthesized and tested between 1960 and 1965 through an international cooperation between Wyeth, USA and Schering, Berlin. It is a mixture of two "enantiomers," with only one form (designated as levonorgestrel) biologically active. When taken orally, it is rapidly absorbed, not subjected to a "first-pass" effect and is approximately 90% bioavailable, with a circulating half-life around 15 hours. Its contraceptive action is exerted at the central (hypothalamic) and peripheral (cervical mucus and endometrium) levels. Levonorgestrel (LNG), alone or in combination with ethinyl estradiol (EE), is the most widely employed contraceptive progestin: it is used in combined oral contraceptives, progestogen-only pills, long-acting contraceptive implants, intrauterine contraceptive systems and in emergency contraception. It is also the steroid of choice for new oral contraceptive regimens aimed at reducing the frequency of bleeding episodes. This novel approach, already tried more than 30 years ago, gained interest around the year 2000 when surveys of women's attitudes toward monthly menstrual bleeding started to show a major change: more and more women declared that they would welcome a hormonal contraceptive method that reduced bleeding episodes to 4, 2 or even 1 per year. At this point, while the debate on the significance and "usefulness" of menstruation went on, attention focused on new regimens. The first new modality consisted of changing the 7-day medication-free interval, either shortening it to fewer than 7 days, or by the administration of low-dose estrogens during the interval between packages. Then, continuous administration regimens started to be investigated. This, however, did not happen suddenly, since, in specific situations, doctors had for years empirically utilized various continuous administration regimens. The first extended-cycle oral contraceptive regimen introduced in clinical practice is an 84-day regimen that results in bleeding only 4 times a year. A commercial product specifically packed for continuous use is now available in Europe and contains 30 μg EE and 150 μg LNG. In a variation of this regimen, after administration of the same combination for 84 days, women are given 7 pills containing 10 μg EE. A 6-monthly regimen has also been tested in a small study using EE 20 μg plus LNG 100 μg taken with and without a hormone-free interval. Women in the continuous group reported significantly fewer bleeding days requiring protection and were more likely to have amenorrhea; in addition they also reported significantly fewer days of bloating and menstrual pain. A yearly regimen is now being developed. Each pill of this novel formulation contains EE 20 μg and LNG 90 μg to be taken continuously for 364 days (13 cycles) per year. A phase III trial has now evaluated safety, efficacy and menses inhibition. At the end of the 1-year trial amenorrhea was present in 58.7% of the women and a complete absence of bleeding in 79.0%. Overall, the number of bleeding and spotting days per pill pack declined with time and adverse events and discontinuations were comparable to those reported for cyclic oral contraceptive regimens.
levonorgestrel; oral contraceptive; continuous administration; menstruation; amenorrhea
Related Articles
Weight Change at 12 Months in Users of Three Progestin-Only Contraceptive Methods
Vickery, Zevidah
Madden, Tessa
Zhao, Qiuhong
Secura, Gina
Allsworth, Jenifer E.
Peipert, Jeffrey F.
Concerns about weight gain may influence contraceptive use. We compared the change in body weight over the first 12 months of use between women using the etonogestrel (ENG) implant, the levonorgestrel intrauterine system (LNG-IUS), or depot medroxyprogesterone acetate (DMPA) with women using the copper intrauterine device (IUD).
Study Design
This was a substudy of the Contraceptive CHOICE Project, a prospective cohort study of 9256 women provided no-cost contraception. Women who had been using the ENG implant, LNG-IUS, DMPA, or copper IUD continuously for at least 11 months were eligible for participation. We obtained body weight at enrollment and at 12 months and compared the weight change for each progestin-only method to the copper IUD.
We enrolled a total of 427 women: 130 ENG implant users, 130 LNG-IUS users, 67 DMPA users, and 100 copper IUD users. The mean weight change (in kilograms) over 12 months was 2.1 for ENG implant users (standard deviation [SD] 6.7); 1.0 for LNG-IUS users (SD 5.3); 2.2 for DMPA users (SD 4.9); and 0.2 for copper IUD users (SD 5.1). The range of weight change was broad across all contraceptive methods. In the unadjusted linear regression model, ENG implant and DMPA use was associated with weight gain compared to the copper IUD. However, in the adjusted model, no difference in weight gain with the ENG implant, LNG-IUS, or DMPA was observed. Only black race was associated with significant weight gain (1.3 kg, 95% CI 0.2-2.4) when compared to other racial groups.
Weight change was variable among women using progestin-only contraceptives. Black race was a significant predictor of weight gain among contraceptive users.
Related Articles
Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093
Watts, D Heather
Park, Jeong-Gun
Cohn, Susan E
Yu, Song
Hitti, Jane
Stek, Alice
Clax, Pamela A.
Muderspach, Laila
Lertora, Juan JL
Concomitant use of antiretrovirals (ARV) and hormonal contraceptives may change the metabolism of each and the resulting safety profiles. We evaluated the safety and tolerability of depot medroxyprogesterone acetate (DMPA) among women on ARV.
Study Design
HIV-infected women on selected ARV regimens or no ARV were administered DMPA 150 mg intramuscularly and evaluated for 12 weeks for adverse events, changes in CD4+ count and HIV RNA levels, and ovulation.
Seventy evaluable subjects were included, 16 on nucleoside only or no ARV, 21 on nelfinavir-containing regimens, 17 on efavirenz-containing regimens, and 16 on nevirapine-containing regimens. Nine grade 3 or 4 adverse events occurred in 7 subjects; none were judged related to DMPA. The most common findings possibly related to DMPA were abnormal vaginal bleeding (9, 12.7%), headache (3, 4.2%), abdominal pain, mood changes, insomnia, anorexia, and fatigue, each occurring in 2 (2.9%) subjects. No significant changes in CD4+ count or HIV RNA levels occurred with DMPA. No evidence of ovulation was detected, and no pregnancies occurred.
The clinical profile associated with DMPA administration in HIV-infected women, most on ARV, appears similar to that seen in HIV-uninfected women. DMPA prevented ovulation and did not affect CD4+ counts or HIV RNA levels. In concert with previously published DMPA/ARV interaction data, these data suggest that DMPA can be used safely by HIV-infected women on the ARV studied.
HIV; women; depotmedroxyprogesterone; antiretrovirals; contraception 1
Related Articles
HIV-1 Drug Resistance Emergence among Breastfeeding Infants Born to HIV-Infected Mothers during a Single-Arm Trial of Triple-Antiretroviral Prophylaxis for Prevention of Mother-To-Child Transmission: A Secondary Analysis
Zeh, Clement
Weidle, Paul J.
Nafisa, Lillian
Lwamba, Humphrey M.
Okonji, Jully
Anyango, Emily
Bondo, Philip
Masaba, Rose
Fowler, Mary Glenn
Nkengasong, John N.
Thigpen, Michael C.
Thomas, Timothy
PLoS Medicine
Analysis of a substudy of the Kisumu breastfeeding trial by Clement Zeh and colleagues reveals the emergence of HIV drug resistance in HIV-positive infants born to HIV-infected mothers treated with antiretroviral drugs.
Nevirapine and lamivudine given to mothers are transmitted to infants via breastfeeding in quantities sufficient to have biologic effects on the virus; this may lead to an increased risk of a breastfed infant's development of resistance to maternal antiretrovirals. The Kisumu Breastfeeding Study (KiBS), a single-arm open-label prevention of mother-to-child HIV transmission (PMTCT) trial, assessed the safety and efficacy of zidovudine, lamivudine, and either nevirapine or nelfinavir given to HIV-infected women from 34 wk gestation through 6 mo of breastfeeding. Here, we present findings from a KiBS trial secondary analysis that evaluated the emergence of maternal ARV-associated resistance among 32 HIV-infected breastfed infants.
Methods and Findings
All infants in the cohort were tested for HIV infection using DNA PCR at multiple study visits during the 24 mo of the study, and plasma RNA viral load for all HIV-PCR–positive infants was evaluated retrospectively. Specimens from mothers and infants with viral load >1,000 copies/ml were tested for HIV drug resistance mutations. Overall, 32 infants were HIV infected by 24 mo of age, and of this group, 24 (75%) infants were HIV infected by 6 mo of age. Of the 24 infants infected by 6 mo, nine were born to mothers on a nelfinavir-based regimen, whereas the remaining 15 were born to mothers on a nevirapine-based regimen. All infants were also given single-dose nevirapine within 48 hours of birth. We detected genotypic resistance mutations in none of eight infants who were HIV-PCR positive by 2 wk of age (specimens from six infants were not amplifiable), for 30% (6/20) at 6 wk, 63% (14/22) positive at 14 wk, and 67% (16/24) at 6 mo post partum. Among the 16 infants with resistance mutations by 6 mo post partum, the common mutations were M184V and K103N, conferring resistance to lamivudine and nevirapine, respectively. Genotypic resistance was detected among 9/9 (100%) and 7/15 (47%) infected infants whose mothers were on nelfinavir and nevirapine, respectively. No mutations were detected among the eight infants infected after the breastfeeding period (age 6 mo).
Emergence of HIV drug resistance mutations in HIV-infected infants occurred between 2 wk and 6 mo post partum, most likely because of exposure to maternal ARV drugs through breast milk. Our findings may impact the choice of regimen for ARV treatment of HIV-infected breastfeeding mothers and their infected infants.
Trial Registration
ClinicalTrials.gov NCT00146380
Please see later in the article for the Editors' Summary
Editors' Summary
Globally, more than 2 million children are infected with the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS), and half a million children are newly infected every year. These infections are mainly the result of mother-to-child transmission (MTCT) of HIV during pregnancy, labor and delivery, or through breastfeeding. MTCT can be greatly reduced by treating HIV-positive mothers and their babies with antiretroviral drugs (ARVs). Without ARVs, up to half of babies born to HIV-positive mothers become infected with HIV. This rate of transmission falls to below 5% if a combination of three ARVs is given to the mother throughout pregnancy. Unfortunately, this triple-ARV therapy is too expensive for use in the resource-limited countries where most MTCT occurs. Instead, many such countries have introduced simpler, shorter ARV regimens such as a daily dose of zidovudine (a nucleoside reverse transcriptase inhibitor or NRTI) given to HIV-positive women during late pregnancy coupled with single-dose nevirapine (a non-nucleoside reverse transcriptase inhibitor or NNRTI) at the onset of labor, zidovudine and lamivudine (another NRTI) during labor and delivery, and single-dose nevirapine given to the baby at birth.
Why Was This Study Done?
More than 95% of HIV-exposed children are born in resource-limited settings where breastfeeding is the norm and is crucial for child survival even though it poses a risk of HIV transmission. Consequently, several recent studies have investigated whether MTCT can be further reduced by giving the mother ARVs while she is breastfeeding. In the Kisumu Breastfeeding Study (KiBS), for example, researchers assessed the effects of giving zidovudine, lamivudine, and either nevirapine or nelfinavir (a protease inhibitor) to HIV-infected women from 34 weeks of pregnancy through 6 months of breastfeeding. The results of KiBS indicate that this approach might be a safe, feasible way to reduce MTCT (see the accompanying paper by Thomas and colleagues). However, low amounts of nevirapine and lamivudine are transferred from mother to infant in breast milk and this exposure to ARVs could induce the development of resistance to ARVs among HIV-infected infants. In this KiBS substudy, the researchers investigate whether HIV drug resistance emerged in any of the HIV-positive infants in the parent study.
What Did the Researchers Do and Find?
In KiBS, 32 infants were HIV-positive at 24 months old; 24 were HIV-positive at 6 months old when their mothers stopped taking ARVs and when breastfeeding was supposed to stop. The researchers analyzed blood samples taken from these infants at various ages and from their mothers for the presence of HIV drug resistance mutations (DNA changes that make HIV resistant to killing by ARVs). They detected no resistance mutations in samples taken from 2-week old HIV-positive infants or from the infants who became infected after the age of 6 months. However, they found resistance mutations in a third and two-thirds of samples taken from 6-week and 6-month old HIV-positive infants, respectively. The commonest mutations conferred resistance to lamivudine and nevirapine. Moreover, resistance mutations were present in samples taken from all the HIV-positive infants whose mothers who had received nelfinavir but in only half those taken from infants whose mothers who had received nevirapine. Finally, most of the mothers of HIV-positive infants had no HIV drug resistance mutations, and only one mother-infant pair had an overlapping pattern of HIV drug resistance mutations.
What Do These Findings Mean?
These findings indicate that, in this KiBS substudy, the emergence of HIV drug resistance mutations in HIV-infected infants whose mothers were receiving ARVs occurred between 2 weeks and 6 months after birth. The pattern of mutations suggests that drug resistance most likely arose through exposure of the infants to low levels of ARVs in breast milk rather than through MTCT of drug-resistant virus. These findings need confirming but suggest that infants exposed to ARVs through breast milk—a situation that may become increasingly common given the reduction in MTCT seen in KiBS and other similar trials—should be carefully monitored for HIV infection. Providers should consider the mothers' regimen when choosing treatment for infants who are found to be HIV-infected despite maternal triple drug prophylaxis. Infants exposed to a maternal regimen with NNRTI drugs should receive first-line therapy with lopinavir/ritonavir, a protease inhibitor. The significance of the NRTI mutations such as M184V with regard to response to therapy needs further evaluation. The M184V mutation may result in hypersensitization to other NRTI drugs and delay or reverse zidovudine resistance. Given the limited availability of alternative drugs for infants in resource-limited settings, provision of the standard WHO-recommended first-line NRTI backbone, which includes 3TC, with enhanced monitoring of the infant to ensure virologic suppression, could be considered. Such an approach should reduce both illness and morbidity among infants who become HIV positive through breastfeeding.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1000430.
The accompanying PLoS Medicine Research article by Thomas and colleagues describes the primary findings of the Kisumu Breastfeeding Study
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on HIV/AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on children, HIV, and AIDS and on preventing mother-to-child transmission of HIV (in English and Spanish)
UNICEF also has information about children and HIV and AIDS (in several languages)
The World Health organization has information on mother-to-child transmission of HIV (in several languages), and guidance on the use of ARVs for preventing MTCT
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A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception
Shohel, Mohammad
Rahman, Mohammad Mahfuzur
Zaman, Asif
Uddin, Mir Muhammad Nasir
Al-Amin, Md Mamun
Reza, Hasan Mahmud
BMC Women's Health
Unintended pregnancy is a complex phenomenon which raise to take an emergency decision. Low contraceptive prevalence and high user failure rates are the leading causes of this unexpected situation. High user failure rates suggest the vital role of emergency contraception to prevent unplanned pregnancy. Levonorgestrel - a commonly used progestin for emergency contraception. However, little is known about its pharmacokinetics and optimal dose for use. Hence, there is a need to conduct a systematic review of the available evidences.
Randomized, double-blind trials were sought, evaluating healthy women with regular menstrual cycles, who requested emergency contraception within 72 h of unprotected coitus, to one of three regimens: 1.5 mg single dose levonorgestrel, two doses of 0.75 mg levonorgestrel given 12 h apart or two doses of 0.75 mg levonorgestrel given 24 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation.
Every trial under consideration successfully established the contraceptive effectiveness of levonorgestrel for preventing unintended pregnancy. Moreover, a single dose of levonorgestrel 1.5 mg for emergency contraception supports its safety and efficacy profile. If two doses of levonorgestrel 0.75 mg are intended for administration, the second dose can positively be taken 12–24 h after the first dose without compromising its contraceptive efficacy. The main side effect was frequent menstrual irregularities. No serious adverse events were reported.
The review shows that, emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen. All the regimens studied were very efficacious for emergency contraception and prevented a high proportion of pregnancies if taken within 72 h of unprotected coitus. Single levonorgestrel dose (1.5 mg) can substitute two 0.75 mg doses 12 or 24 h apart. With either regimen, the earlier the treatment is given, the more effective it seems to be.
Levonorgestrel; Oral contraceptive; Emergency contraception; Two dose regimen; Postcoital contraception; Single dose strategy; Contraceptive efficacy; Unintended pregnancy; Postcoital hormonal contraceptives
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Contraceptive Methods and Risk of HIV Acquisition or Female-to-Male Transmission
Haddad, Lisa B.
Polis, Chelsea B.
Sheth, Anandi N.
Brown, Jennifer
Kourtis, Athena P.
King, Caroline
Chakraborty, Rana
Ofotokun, Igho
Current HIV/AIDS reports
Effective family planning with modern contraception is an important intervention to prevent unintended pregnancies which also provides personal, familial, and societal benefits. Contraception is also the most cost-effective strategy to reduce the burden of mother-to-child HIV transmission for women living with HIV who wish to prevent pregnancy. There are concerns, however, that certain contraceptive methods, in particular the injectable contraceptive depot medroxyprogesterone acetate (DMPA), may increase a woman's risk of acquiring HIV or transmitting it to uninfected males. These concerns, if confirmed, could potentially have large public health implications. This paper briefly reviews the literature on use of contraception among women living with HIV or at high risk of HIV infection. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) recommendations place no restrictions on the use of hormonal contraceptive methods by women with or at high risk of HIV infection, although a clarification recommends that, given uncertainty in the current literature, women at high risk of HIV who choose progestogen-only injectable contraceptives should be informed that it may or may not increase their risk of HIV acquisition and should also be informed about and have access to HIV preventive measures, including male or female condoms.
HIV; AIDS; Contraception; Hormonal contraception; Transmission
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Continuation and Satisfaction of Reversible Contraception
Peipert, Jeffrey F.
Zhao, Qiuhong
Allsworth, Jenifer E.
Petrosky, Emiko
Madden, Tessa
Eisenberg, David
Secura, Gina
Obstetrics and gynecology
To estimate 12-month satisfaction and continuation rates of intrauterine device (IUD) and implant users enrolled in the Contraceptive CHOICE Project and compare these measures to women using the oral contraceptive pills (OCPs).
We analyzed 12-month data from the first 5,087 participants enrolled in a prospective cohort study of women in the St. Louis region offered contraception at no cost for 3 years. The primary purpose of CHOICE is to promote the use of long-acting reversible contraception (IUDs and implants) and to reduce unintended pregnancies in our region. This analysis includes participants who received their baseline contraceptive method within 3 months of enrollment and who reached the 12-month follow-up phone survey time point (N=4,167).
Sixty-eight percent of our participants chose a long-acting reversible contraception method (45% levonorgestrel intrauterine system, 10% copper IUD, and 13% subdermal implant), while 23% chose combined hormonal methods (11% OCPs, 10% vaginal ring, and 2% transdermal patch), and 8% chose depot medroxyprogesterone acetate. Long-acting reversible contraception users had higher 12-month continuation rates (86%) than OCP users (55%). The two IUDs had the highest 12-month continuation rates: levonorgestrel intrauterine system (88%) and copper IUD (84%). Women using the implant also had very high rates of continuation at 1 year (83%). Satisfaction mirrored continuation: over 80% of users were satisfied with the IUD compared to 54% satisfied with OCPs.
IUDs and the subdermal implant have the highest rates of satisfaction and 12-month continuation. Given that long-acting reversible contraception methods have the highest contraceptive efficacy, these methods should be the first-line contraceptive methods offered to patients.
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Medical eligibility, contraceptive choice, and intrauterine device acceptance among HIV-infected women receiving antiretroviral therapy in Lilongwe, Malawi
Haddad, Lisa B.
Feldacker, Caryl
Jamieson, Denise J.
Tweya, Hannock
Cwiak, Carrie
Bryant, Amy G.
Hosseinipour, Mina C.
Chaweza, Thomas
Mlundira, Linly
Kachale, Fanny
Stuart, Gretchen S.
Hoffman, Irving
Phiri, Sam
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics
To determine medical eligibility for contraceptive use, contraceptive preference, and acceptance of a copper intrauterine device (IUD) among a cohort of HIV-infected women receiving antiretroviral therapy (ART).
All HIV-infected women who received ART and sought contraceptive services at the Lighthouse clinic, an integrated HIV/ART clinic in Lilongwe, Malawi, between August and December 2010 were invited to participate in a structured interview. Eligibility and preference for the following contraceptive methods were assessed: combined hormonal contraceptives, progestogen-only pills, copper IUD, injectable depot medroxyprogesterone acetate (DMPA), and contraceptive implants.
The final sample included 281 women; five were pregnant. The remaining 276 women were eligible for at least three contraceptive methods, with 242 (87.7%) eligible for all five methods evaluated. After counseling, 163 (58.0%) selected DMPA and 98 (34.9%) selected an IUD as their preferred contraceptive method. Regardless of their method of choice, 222 (79.0%) women agreed to have an IUD placed on the same day.
Most methods of contraception are safe for use by HIV-infected women. Approximately 80% of the women were willing to receive an IUD. Efforts must be made to increase education about, and access to, long-acting reversible methods that may be acceptable and appropriate contraceptive options for HIV-infected women.
Antiretroviral therapy; Contraception; HIV; Intrauterine contraception; Intrauterine device; Malawi; Medical eligibility
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Twenty-Four–Month Continuation of Reversible Contraception
O'Neil, Micaela E.
Peipert, Jeffrey F.
Zhao, Qiuhong
Madden, Tessa
Secura, Gina
Obstetrics and gynecology
To estimate 24-month continuation rates of all reversible contraceptive methods for women enrolled in the Contraceptive CHOICE Project.
We analyzed 24-month data from the 9,256 participants enrolled in the Contraceptive CHOICE Project, a prospective observational cohort study that provides no-cost contraception to women in the St. Louis region. The project promoted the use of long-acting reversible contraception (LARC; intrauterine devices (IUDs) and implants) in an effort to reduce the rates of unintended pregnancy. This analysis includes participants who received their baseline contraceptive method within 3 months of enrollment and who completed a 24-month follow-up survey (n=6,153).
Twenty-four month continuation rates for LARC and non-LARC methods were 77% and 41%, respectively. Continuation rates for the levonorgestrel and the copper IUDs were similar (79% versus 77%), whereas the implant continuation rate was significantly lower (69%, p<0.001) compared to IUDs at 24 months. There was no statistically significant difference in 24-month continuation rates among the four non-LARC methods (oral contraceptive pill 43%, patch 40%, ring 41%, depot medroxyprogesterone acetate (DMPA) 38%, p=0.72). Participants who chose a LARC method at enrollment were at significantly lower risk of contraceptive method discontinuation (adjusted hazard ratio=0.29, 95% confidence interval 0.26, 0.32) compared with women who selected a non-LARC method.
IUDs and the implant have the highest rates of continuation at 24-months. Given their effectiveness and high continuation rates, IUDs and implants should be first-line contraceptive options and shorter-acting methods such as OCPs, patch, ring, and DMPA should be second tier.
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Efficacy and safety of a levonorgestrel enteric-coated tablet as an over-the-counter drug for emergency contraception: a Phase IV clinical trial
Chen, Q.-J.
Xiang, W.-P.
Zhang, D.-K.
Wang, R.-P.
Luo, Y.-F.
Kang, J.-Z.
Cheng, L.-N.
Human Reproduction (Oxford, England)
An enteric-coated levonorgestrel emergency contraceptive pill (E-LNG-ECP) is an improved formulation, in terms of side effects, which both dissolves and is absorbed in the intestine. Our aim was to evaluate the efficacy and safety of E-LNG-ECP as an over-the-counter (OTC) drug for emergency contraception (EC) in Chinese women.
A Phase IV clinical trial was conducted in five family planning clinics in China. Women seeking EC within 72 h after unprotected sexual intercourse or contraceptive failure who met the inclusion criteria were recruited. The efficacy of contraception (primary end-point was pregnancy rate), side effects (i.e. safety) and the value of E-LNG-ECP for EC were investigated.
Of 2445 women (aged 15–48 years) who took E-LNG-ECP with follow-up to determine pregnancy, only five pregnancies (0.2%) occurred. The efficacy of contraception was 95.3%. In total, 6.5% of women reported at least one adverse event after taking E-LNG-ECP, and no serious adverse events were reported. Only four subjects (0.16%) reported vomiting. The incidence of menstrual cycle disturbance was 20.1% after taking E-LNG-ECP. Subjects who had previously taken ECPs (54.4% of these women) rated the acceptability of E-LNG-ECP at 9.36 (on a 10-point scale) higher (P<0.05) than the rating of other LNG-EC pills taken previously.
The study found that E-LNG-ECP was effective, safe and well tolerated as an OTC drug. However, an randomized controlled trial should be performed to compare standard LNG tablets with E-LNG-ECP.
emergency contraception; levonorgestrel enteric-coated tablet; over-the-counter drug; clinical trial
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Introduction of the levonorgestrel intrauterine system in Kenya through mobile outreach: review of service statistics and provider perspectives
Hubacher, David
Akora, Vitalis
Masaba, Rose
Chen, Mario
Veena, Valentine
Global Health, Science and Practice
Limited introduction of the LNG IUS through mobile outreach in Kenya, without any special promotion, resulted in good uptake. And providers viewed it positively, particularly because of its noncontraceptive benefits. Increased provision of the LNG IUS can improve options for women needing highly effective reversible contraception.
Limited introduction of the LNG IUS through mobile outreach in Kenya, without any special promotion, resulted in good uptake. And providers viewed it positively, particularly because of its noncontraceptive benefits. Increased provision of the LNG IUS can improve options for women needing highly effective reversible contraception.
The levonorgestrel intrauterine system (LNG IUS) was developed over 30 years ago, but the product is currently too expensive for widespread use in many developing countries. In Kenya, one organization has received donated commodities for 5 years, providing an opportunity to assess impact and potential future role of the product.
We reviewed service statistics on insertions of the LNG IUS, copper intrauterine device (IUD), and subdermal implant from 15 mobile outreach teams during the 2011 calendar year. To determine the impact of the LNG IUS introduction, we analyzed changes in uptake and distribution of the copper IUD and subdermal implant by comparing periods of time when the LNG IUS was available with periods when it was not available. In addition, we interviewed 27 clinicians to assess their views of the product and of its future role.
When the LNG IUS was not available, intrauterine contraception accounted for 39% of long-acting method provision. The addition of the LNG IUS created a slight rise in intrauterine contraception uptake (to 44%) at the expense of the subdermal implant, but the change was only marginally significant (P = .08) and was largely attributable to the copper IUD. All interviewed providers felt that the LNG IUS would increase uptake of long-acting methods, and 70% felt that the noncontraceptive benefits of the product are important to clients.
The LNG IUS was well-received among providers and family planning clients in this population in Kenya. Although important changes in service statistics were not apparent from this analysis (perhaps due to the small quantity of LNG IUS that was available), provider enthusiasm for the product was high. This finding, above all, suggests that a larger-scale introduction effort would have strong support from providers and thus increase the chances of success. Adding another proven and highly acceptable long-acting contraceptive technology to the method mix could have important reproductive health impact.
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Contraceptive Choices, Pregnancy Rates, and Outcomes in a Microbicide Trial
Sibeko, Sengeziwe
Baxter, Cheryl
Yende, Nonhlanhla
Karim, Quarraisha Abdool
Karim, Salim S Abdool
Obstetrics and gynecology
Women who become pregnant during the conduct of biomedical HIV prevention trials are taken off the study product for safety reasons. High pregnancy rates can compromise statistical integrity in these trials. The comprehensive contraceptive curriculum developed for the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial was evaluated for its ability to enhance contraceptive uptake, reduce pregnancy rates, and preserve statistical integrity.
Contraceptive- and pregnancy-related eligibility criteria were specified in the protocol. We enrolled women who opted for a non-barrier method of contraceptive and provided hormonal contraceptives on-site at no cost. At each monthly study visit, we provided pregnancy prevention counselling and performed pregnancy testing. Study product was withheld on pregnancy diagnosis, but women continued with monthly follow-up.
Contraceptive usage was high throughout the study with 100% uptake at baseline and 94.71% use after a mean of 18 months follow-up at exit. Injectable progestins, particularly medroxyprogesterone acetate, remained the preferred choice of contraceptive. After 30 months of follow-up, 54 pregnancies were reported out of 889 participants, giving a pregnancy incidence rate of 3.95 per 100 woman-years (95% CI: 2.96 to 5.17). Of all pregnancies, 2/3 (64.81%) resulted in a full-term live birth, while 18.52% and 11.11% pregnancies culminated as miscarriage and terminated pregnancies, respectively. There were no congenital anomalies in the early neonatal period. Pregnancies resulted in 1.56% of woman-years of study follow-up lost due to temporary product withdrawal.
The CAPRISA 004 contraceptive curriculum was an effective strategy for maintaining low pregnancy rates, thereby minimizing product withdrawal and loss of follow-up time.
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Injectable and Oral Contraceptive Use and Cancers of the Breast, Cervix, Ovary, and Endometrium in Black South African Women: Case–Control Study
Urban, Margaret
Banks, Emily
Egger, Sam
Canfell, Karen
O'Connell, Dianne
Beral, Valerie
Sitas, Freddy
PLoS Medicine
A case-control study conducted in South Africa provides new estimates of the risk of specific cancers of the female reproductive system associated with use of injectable and oral contraceptives.
Oral contraceptives are known to influence the risk of cancers of the female reproductive system. Evidence regarding the relationship between injectable contraceptives and these cancers is limited, especially in black South Africans, among whom injectable contraceptives are used more commonly than oral contraceptives.
Methods and Findings
We analysed data from a South African hospital-based case–control study of black females aged 18–79 y, comparing self-reported contraceptive use in patients with breast (n = 1,664), cervical (n = 2,182), ovarian (n = 182), and endometrial (n = 182) cancer, with self-reported contraceptive use in 1,492 control patients diagnosed with cancers with no known relationship to hormonal contraceptive use. We adjusted for potential confounding factors, including age, calendar year of diagnosis, education, smoking, alcohol, parity/age at first birth, and number of sexual partners. Among controls, 26% had used injectable and 20% had used oral contraceptives. For current and more recent users versus never users of oral or injectable contraceptives, the odds ratios (ORs) for breast cancer were significantly increased in users of oral and/or injectable contraceptives (OR 1.66, 95% CI 1.28–2.16, p<0.001) and separately among those exclusively using oral (1.57, 1.03–2.40, p = 0.04) and exclusively using injectable (OR 1.83, 1.31–2.55, p<0.001) contraceptives; corresponding ORs for cervical cancer were 1.38 (1.08–1.77, p = 0.01), 1.01 (0.66–1.56, p = 0.96), and 1.58 (1.16–2.15, p = 0.004). There was no significant increase in breast or cervical cancer risk among women ceasing hormonal contraceptive use ≥10 y previously (p = 0.3 and p = 0.9, respectively). For durations of use ≥5 y versus never use, the ORs of ovarian cancer were 0.60 (0.36–0.99, p = 0.04) for oral and/or injectable contraceptive use and 0.07 (0.01–0.49, p = 0.008) for injectable use exclusively; corresponding ORs for endometrial cancer were 0.44 (0.22–0.86, p = 0.02) and 0.36 (0.11–1.26, p = 0.1).
In this study, use of oral and of injectable hormonal contraceptives was associated with a transiently increased risk of breast and cervical cancer and, for long durations of use, with a reduced risk of ovarian and endometrial cancer. The observed effects of injectable and of oral contraceptives on cancer risk in this study did not appear to differ substantially.
Please see later in the article for the Editors' Summary
Editors' Summary
Hormonal contraceptives are among the most commonly used medications. Globally, more than 210 million women currently use either hormonal contraceptive pills or injectable contraceptives. Contraceptive pills usually contain manmade versions of the female sex hormones estrogen and progesterone (the combined oral contraceptive, or "pill"); most injectable hormonal contraceptives contain only manmade progesterone preparations. Hormonal contraceptives, which prevent pregnancy by disrupting the cyclical changes in estrogen and progesterone levels that prepare the body for pregnancy, have revolutionized birth control since they first became available in the early 1960s. However, it is now known that taking the pill also influences women's risk of developing cancers of the female reproductive system. Current and recent users have an increased risk of developing breast and cervical cancer (the cervix is the structure that connects the womb to the vagina) compared to never users, although this increased risk quickly disappears when women stop taking the pill. By contrast, women who have used the pill have a reduced risk of developing ovarian cancer and cancer of the womb (endometrial cancer) compared to never users that increases with the duration of pill use and persists for many years after use ceases. These effects on reproductive system cancers are thought to occur because these cancers depend on naturally occurring sex hormones for their development and growth.
Why Was This Study Done?
Although the evidence that the pill influences the risk of developing cancers of the female reproductive system is extensive, much less is known about how injectable hormonal contraceptives affect cancer risk. In this hospital-based case–control study (a study that compares the characteristics of people with and without a specific condition), the researchers investigate the relationship between the use of oral and injectable hormonal contraceptives and cancers of the breast, cervix, ovary, and endometrium among black South African women. Injectable contraceptives have been used for longer in South Africa than elsewhere and are used more commonly than oral contraceptives among black South African women.
What Did the Researchers Do and Find?
As part of the Johannesburg Cancer Case Control Study, which recruits black patients attending Johannesburg public referral hospitals for cancer treatment, the researchers compared hormonal contraceptive use in women with breast, cervical, ovarian, or endometrial cancer with contraceptive use in women diagnosed with other cancers such as lung, colon, and rectal cancers, which are not known to be influenced by hormonal contraceptives. Among the controls, a quarter had used injectable contraceptives and a fifth had used oral contraceptives. After adjusting for other factors that might influence cancer risk such as age, smoking, and number of sexual partners, the odds ratio (OR) of breast cancer among current and recent users of oral and/or injectable contraceptives compared to never users was 1.66. That is, the risk of developing breast cancer among current and recent users of hormonal contraceptives was 1.66 times that among never users. For women using oral contraceptives exclusively or injectable contraceptives exclusively, the ORs of breast cancer were 1.57 and 1.83, respectively. There were also increases in cervical cancer risk among current and recent users of hormonal contraceptives compared to never users, but no significant increase in breast or cervical cancer risk among women who had ceased hormonal contraceptive use more than ten years previously. Finally, the use of hormonal contraceptives for more than five years reduced the risk of both ovarian and endometrial cancer.
What Do These Findings Mean?
These findings indicate that, among black women in South Africa, the use of oral or injectable hormonal contraceptives is associated with a transiently increased risk of breast and cervical cancer, and that extended use of these contraceptives is associated with a reduced risk of ovarian and endometrial cancer. Moreover, they suggest that the effects of oral versus injectable contraceptives on cancer risk do not differ substantially, although for endometrial and ovarian cancer the small number of cases exposed to injectable contraceptives limits the accuracy of the risk estimates. Other limitations of this study include the possibility that the findings may be affected by uncontrolled confounding. That is, women who used hormonal contraceptives may have shared other unidentified characteristics that affected their cancer risk. Nevertheless, these findings provide new information about the effects of oral and injectable hormonal contraceptives on cancer risk that should help women make informed decisions about their choice of contraceptive method.
Additional Information
Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001182.
The US National Cancer Institute provides information on breast cancer (including personal stories from breast cancer survivors), cervical cancer, ovarian cancer, and endometrial cancer for patients and health professionals, and a fact sheet on oral contraceptives and cancer risk (in English and Spanish)
Cancer Research UK also provides information on breast cancer, cervical cancer, ovarian cancer, and endometrial cancer and information about the birth control pill and cancer risk
Eyes on the Prize, an online support group for women who have had cancers of the female reproductive system, has personal stories; further personal stories about breast, cervical, and ovarian cancer are provided by the charity Healthtalkonline
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Injectable and oral contraceptives and risk of HIV acquisition in women: an analysis of data from the MDP301 trial
Crook, Angela M.
Ford, Deborah
Gafos, Mitzy
Hayes, Richard
Kamali, Anatoli
Kapiga, Saidi
Nunn, Andrew
Chisembele, Maureen
Ramjee, Gita
Rees, Helen
McCormack, Sheena
Human Reproduction (Oxford, England)
Do injectable and oral contraceptives increase the risk of human immunodeficiency virus (HIV) acquisition in women?
After adjusting for confounders, evidence of a significantly increased risk of HIV remained for women using injectable depo-medroxyprogesterone (DMPA) (hazard ratio = 1.49, 95% confidence interval (1.06–2.08)) but not for injectable norethisterone-enanthate (Net-En) or oral contraceptive pills (OC).
An association between the use of some types of hormonal contraception (HC) methods and an increased risk of HIV, possibly through changes in the genital tract environment and alterations in the immune response, has been previously observed, although not consistently. A recent systematic review of these studies has highlighted the need for more definitive evidence.
A secondary data analysis of the MDP301 phase 3 microbicide trial was conducted to estimate the effects of use of different methods of HC on the risk of HIV acquisition in women. HIV-negative women (n = 8663) with a median age of 28 years were included in the analysis; 382 HIV seroconverted by 52 weeks follow-up; 10% of women-years were lost to follow-up before 52 weeks.
Contraceptive use was reported at each 4-weekly visit. Cox proportional hazards (PH) models were used to estimate the effects of baseline and current use of injectable DMPA, injectable Net-En and OC compared with no HC, on the risk of HIV, adjusting for baseline and time-updated covariates. Causal effects for 52 weeks of HC use compared with no HC were estimated in a weighted Cox model, censoring women at deviation from baseline HC use (or non-use) or pregnancy.
At baseline, 2499 (29%) women were on DMPA, 1180 (14%) on Net-En, and 1410 (16%) on OC; 3574 (40%) not on HC, started HC in follow-up. Adjusted hazard ratios (HR) for baseline HC use, compared with no HC, were 1.38 (95% confidence interval (CI) 1.07–1.78) for DMPA; 1.18 (0.86–1.62) for Net-En and 0.97 (0.68–1.38) for OC. The estimated causal effects of DMPA and Net-En over 52 weeks were: HR = 1.49 (95% CI 1.06–2.08) and HR = 1.31 (95% CI 0.62–1.61), respectively.
A main limitation of the study was that it was a secondary analysis of data from a study that was not designed to investigate this question. Despite our best efforts, we cannot exclude residual confounding to explain the effect of DMPA.
The results of this study should be reviewed by the World Health Organization to determine whether current recommendations on the use of DMPA in settings with high HIV prevalence require modification.
MDP is a partnership of African and European academic/government institutions with commercial organizations, which is funded by the UK Government (DFID and MRC), with support from IPM and EDCTP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: None.
HIV; contraception; women; sexual behaviour
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Evolution of Antiretroviral Drug Costs in Brazil in the Context of Free and Universal Access to AIDS Treatment
Nunn, Amy S
Fonseca, Elize M
Bastos, Francisco I
Gruskin, Sofia
Salomon, Joshua A
PLoS Medicine
Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART) for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs), procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005.
Methods and Findings
We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir–ritonavir (lopinavir/r) have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six specific drugs: patented lopinavir/r, efavirenz, tenofovir, atazanavir, enfuvirtide, and a locally produced generic, fixed-dose combination of zidovudine and lamivudine (AZT/3TC). Because prices declined for many of the patented drugs that constitute the largest share of drug costs, nearly the entire increase in overall drug expenditures between 2001 and 2005 is attributable to increases in drug quantities. Had all drug quantities been held constant from 2001 until 2005 (or for those drugs entering treatment guidelines after 2001, held constant between the year of introduction and 2005), total costs would have increased by only an estimated US$7 million. We estimate that in the absence of price declines for patented drugs, Brazil would have spent a cumulative total of US$2 billion on drugs for HAART between 2001 and 2005, implying a savings of US$1.2 billion from price declines. Finally, in comparing Brazilian prices for locally produced generic ARVs to the lowest international prices meeting global pharmaceutical quality standards, we find that current prices for Brazil's locally produced generics are generally much higher than corresponding global prices, and note that these prices have risen in Brazil while declining globally. We estimate the excess costs of Brazil's locally produced generics totaled US$110 million from 2001 to 2005.
Despite Brazil's more costly generic ARVs, the net result of ARV price changes has been a cost savings of approximately US$1 billion since 2001. HAART costs have nevertheless risen steeply as Brazil has scaled up treatment. These trends may foreshadow future AIDS treatment cost trends in other developing countries as more people start treatment, AIDS patients live longer and move from first-line to second and third-line treatment, AIDS treatment becomes more complex, generic competition emerges, and newer patented drugs become available. The specific application of the Brazilian model to other countries will depend, however, on the strength of their health systems, intellectual property regulations, epidemiological profiles, AIDS treatment guidelines, and differing capacities to produce drugs locally.
Amy Nunn and colleagues analyze the cost of antiretroviral drugs in Brazil between 2001 and 2005 and discuss the implications for HIV treatment in other developing countries.
Editors' Summary
Acquired immunodeficiency syndrome (AIDS) has killed 29 million people since the first case occurred in 1981 and an estimated 40 million people live with HIV/AIDS today. AIDS is caused by the human immunodeficiency virus (HIV), which destroys the immune system. Infected individuals are consequently very susceptible to other infections. Early in the AIDS epidemic, most HIV-positive individuals died within a few years of becoming infected. Then, in 1996, highly active antiretroviral therapy (HAART)—a cocktail of antiretroviral drugs (ARVs)—was developed. For people who could afford HAART (which holds HIV infections in check), AIDS became a chronic disease. People who start HAART must keep taking it or their illness will progress.
Unfortunately, few people in low- and middle-income countries could afford these expensive drugs. In 2001, ARV prices fell in developing countries as AIDS activists and developing country governments challenged pharmaceutical companies about ARV prices, pharmaceutical companies set tiered prices for the low- and middle-income countries and more generic (inexpensive copies of brand-named drugs) ARVs became available. In 2003, the lack of access to HIV/AIDS treatment was declared a global health emergency. Governments, international organizations, and funding bodies began to set targets and provide funds to increase access to HAART in developing countries. By 2007, over 2 million people in low- and middle-income countries had access to HAART, but another 5 million remain in urgent need of drugs for treatment.
Why Was This Study Done?
In 1995, many countries in the world signed the World Trade Organization (WTO) Trade-Related Aspects of Intellectual Property (TRIPS) agreement, which requires countries to acknowledge intellectual property rights for many products, including pharmaceuticals. In 1996, Brazil became the first developing country to commit to and implement policies to provide free and universal access to HAART. Since then, Brazil's successful AIDS treatment program has become a model for the developing world, and 180,000 Brazilians were receiving HAART at the end of 2006. However, as a WTO member that signed on to the TRIPS agreement, Brazil was required to recognize the intellectual property rights of pharmaceutical companies' patented ARVs. As Brazil scaled up treatment in the late 1990s, the cost of treating AIDS patients rose quickly and the country took controversial public policy steps to reduce the cost of providing HAART to people living with HIV/AIDS. Brazil produces several non-patented ARVs locally, and since 2001 has challenged multinational pharmaceutical companies about the prices of patented ARVs. To induce price reductions for patented ARVs, Brazil has threatened to issue compulsory licenses (which under WTO terms allow countries facing a health emergency to produce patented drugs without consent of the company holding the patent). Brazil also recently issued a compulsory license for one ARV.
Although world leaders have set a target of universal access to HAART by 2010, little is known about the long-term costs of AIDS treatment in developing countries. In this study, the researchers have investigated how and why the costs of ARVs changed in Brazil between 2001 and 2005 and discuss the relevance of the Brazilian model for AIDS treatment for other resource-limited settings.
What Did the Researchers Do and Find?
The researchers analyzed the prices for each ARV recommended in Brazil's therapeutic guidelines for adults and estimated the changes in purchase quantities for each between 2001 and 2005. These changes likely stem from the growing number of options in Brazil's treatment guidelines, the steadily rising number of patients commencing treatment, and patients' shifts to second- and third-line treatments when their HIV infection became resistant to first-line drugs or they developed side effects. The researchers report that the generic drugs produced in Brazil were generally more expensive than similar drugs made elsewhere, but Brazil's negotiated drug prices for many patented ARVs were lower than elsewhere. Overall, total annual drug expenditure on ARVs doubled between 2001 and 2005, reaching US$414 million in 2005. Because many drug prices fell sharply as a result of declining patented drug prices over the study period, this increase was mainly attributable to increases in drug quantities purchased. If these quantities had stayed constant, the total annual cost would have increased by only $7 million, to $211 million. Conversely, without the decrease in the price of patented drugs, Brazil would have spent $952 million annually by 2005. If Brazil had enjoyed the lowest global prices for generic medicines, the total costs per year in 2005 would have been $367 million, or nearly $50 million less than the costs Brazil actually realized.
What Do These Findings Mean?
These findings tease out the many factors—clinical, commercial, and political—that affected the total costs of the Brazilian AIDS treatment program between 2001 and 2005.
Brazil's ability to produce generic drugs facilitated Brazil's price negotiations for patented drugs. Although Brazil saved approximately US$1 billion over the study period as a result of declining prices for patented medicines, the cost of producing generic drugs locally has risen while the prices for generic drugs have fallen elsewhere. Brazil's recent decision to import a generic ARV using a compulsory license suggests that the Brazilian model for AIDS treatment continues to evolve.
Questions remain about the precise causes of year-to-year cost trends in Brazil because, for example, the researchers did not have full data on when patients switched from first-line to second- or third-line drugs. The observed steep rise in costs from 2004 to 2005 in particular warrants further analysis. In addition, the findings may not be generalizable to countries with different policies on HIV/AIDS treatment, different access to generic drugs, or different bargaining power with multinational drug companies. Nevertheless, the trends this study highlights provide important information about how AIDS treatment costs are likely to evolve in other developing countries as efforts are made to provide universal access to life-saving ARVs.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040305.
Information from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
Information from the US Centers for Disease Control and Prevention on global HIV/AIDS topics (in English and Spanish)
HIV InSite, comprehensive and up-to-date information on all aspects of HIV/AIDS from the University of California San Francisco
Information from Avert, an international AIDS charity, on HIV and AIDS in Brazil and on HIV/AIDS treatment and care, including universal access to ARVs
Progress towards universal access to HIV/AIDS treatment, the latest report from the World Health Organization (available in several languages)
The National STD and AIDS Program of Brazil
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Contraception in HIV-positive female adolescents
Kancheva Landolt, Nadia T
Lakhonphon, Sudrak
Ananworanich, Jintanat
AIDS Research and Therapy
Sexual behavior of HIV-positive youths, whether infected perinatally, through risky behavior or other ways, is not substantially different from that of HIV-uninfected peers. Because of highly active antiretroviral therapy, increasing number of children, infected perinatally, are surviving into adolescence and are becoming sexually active and need reproductive health services. The objective of this article is to review the methods of contraception appropriate for HIV-positive adolescents with a special focus on hormonal contraceptives. Delaying the start of sexual life and the use of two methods thereafter, one of which is the male condom and the other a highly effective contraceptive method such as hormonal contraception or an intrauterine device, is currently the most effective option for those who desire simultaneous protection from both pregnancy and sexually transmitted diseases. Health care providers should be aware of the possible pharmacokinetic interactions between hormonal contraception and antiretrovirals. There is an urgent need for more information regarding metabolic outcomes of hormonal contraceptives, especially the effect of injectable progestins on bone metabolism, in HIV-positive adolescent girls.
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Antiretroviral Treatment and Prevention of Peripartum and Postnatal HIV Transmission in West Africa: Evaluation of a Two-Tiered Approach
Tonwe-Gold, Besigin
Ekouevi, Didier K
Viho, Ida
Amani-Bosse, Clarisse
Toure, Siaka
Coffie, Patrick A
Rouet, François
Becquet, Renaud
Leroy, Valériane
El-Sadr, Wafaa M
Abrams, Elaine J
Dabis, François
PLoS Medicine
Highly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens.
Methods and Findings
The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged ≥ 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%–4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%–9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%–7.0%) at age week 4 wk and 11.7% (95% CI 7.5%–15.9%) at 12 mo.
This two-tiered strategy appears to be safe and highly effective for short- and long-term PMTCT in resource-constrained settings. These results indicate a further benefit of access to HAART for pregnant women who need treatment for their own health.
In an observational cohort study from Côte d'Ivoire, François Dabis and colleagues report on prevention of mother-to-child HIV transmission among women receiving antiretroviral therapy according to World Health Organization recommendations.
Editors' Summary
Effective treatments are available to prevent AIDS in people who are infected with HIV, but not everyone with HIV needs to take medication. Usually, anti-HIV medication is recommended only for those whose immune systems have been significantly affected by the virus, as evidenced by symptoms or by the results of a blood test, the CD4 lymphocyte ("T cell") count. Treating HIV usually requires a combination of three or more medications. These combinations (called HAART) must be taken every day, can cause complications, and can be expensive.
Worldwide, more than half a million children became infected with HIV each year. Most of these children acquire HIV from their mothers during pregnancy or around the time of birth. If a pregnant woman with HIV takes HAART, her chances of passing HIV to the baby are greatly reduced, but the possible side effects of HAART on the baby are not known. Also, most transmission of HIV from mothers to babies occurs in poor countries where supplies of HAART are limited. For these reasons, World Health Organization (WHO) does not recommend that every pregnant woman receive HAART to prevent HIV transmission to the baby, unless the woman needs HAART for her own health (for example if her T cells are low or she has severe symptoms of HIV infection). For pregnant women with HIV who do not need to take HAART for their own health, less complicated treatments, involving a short course of one or two HIV drugs, can be used to reduce the risk of passing HIV to the baby.
Why Was This Study Done?
The WHO recommendations for HAART in pregnancy are based on the best available evidence, but it is important to know how well they work in actual practice. The authors of this study were providing HIV treatment to pregnant women with HIV in West Africa through an established clinic program in Abidjan, Côte d'Ivoire, and wanted to see how well the WHO recommendations for HAART or short-course treatments, depending on the mother's condition, were working to protect babies from HIV infection.
What Did the Researchers Do and Find?
The researchers studied 250 HIV-infected pregnant women who received HIV medications in the Abidjan program between mid-2003 and mid-2005. In accordance with WHO guidelines, 107 women began HAART for their own health during pregnancy, and 143 women did not qualify for HAART but received other short course treatments (scARV) to prevent HIV transmission to their babies. The authors monitored mothers and babies for treatment side effects and tested the babies for HIV infection up to age 1 y.
They found that HAART was relatively safe during pregnancy, although babies born to women on HAART were more likely (26.3%) to have low birth weight than babies born to women who received scARV (12.4%). Also, 7.5% of women on HAART developed side effects requiring a change in their medications. Combining the results from HAART and scART groups, the chance of HIV transmission around the time of birth was 2.2%, increasing to 5.7% at age 1 y. (Three-quarters of the infants were breast-fed; safe water for mixing formula was not reliably available.) The study found no difference in risk of HIV infection between babies whose mothers received HAART and those whose mothers received scARV according to guidelines.
What Do These Findings Mean?
These results support the safety and effectiveness of the WHO two-tiered approach for preventing mother-to-child transmission. This study was not designed to compare HAART to scART directly, because the women who received HAART were the ones with more advanced HIV infection, which might have affected their babies in many ways.
Compared to earlier pregnancy studies of HAART in rich countries, this study of the WHO approach in West Africa showed similar success in protecting infants from HIV infection around the time of birth. Unfortunately, because formula feeding was not generally available in resource-limited settings, protection declined over the first year of life with breast-feeding, but some protection remained.
This study confirms that close monitoring of pregnant women on HAART is necessary, so that drugs can be changed if side effects develop. The study does not tell us whether using scARV in pregnancy might change the virus in ways that would make it more difficult to treat the same women with HAART later if they needed it. The reason for low birth weight in some babies born to mothers on HAART is unclear. It may be because the women who needed HAART had more severe health problems from their HIV, or it may be a result of the HAART itself.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040257.
World Health Organization has a page on prevention of mother-to-child transmission of HIV
"Women, Children, and HIV" is a resource site from the François Xavier Bagnoud Center and UCSF
The MTCT-Plus initiative at Columbia University supports the programs in Abidjan
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Gemzell-Danielsson, Kristina
Meng, Chun-Xia
International Journal of Women's Health
Unintended pregnancy is a global reproductive health problem. Emergency contraception (EC) provides women with a safe means of preventing unwanted pregnancies after having unprotected intercourse. While 1.5 mg of levonorgestrel (LNG) as a single dose or in 2 doses with 12 hours apart is the currently gold standard EC regimen, a single dose of 30 mg ulipristal acetate (UPA) has recently been proposed for EC use up to 120 hours of unprotected intercourse with similar side effect profiles as LNG. The main mechanism of action of both LNG and UPA for EC is delaying or inhibiting ovulation. However, the 'window of effect' for LNG EC seems to be rather narrow, beginning after selection of the dominant follicular and ending when luteinizing hormone peak begins to rise, whereas UPA appears to have a direct inhibitory effect on follicular rupture which allows it to be also effective even when administered shortly before ovulation, a time period when use of LNG is no longer effective. These experimental findings are in line with results from a series of clinical trials conducted recently which demonstrate that UPA seems to have higher EC efficacy compared to LNG. This review summarizes some of the data available on UPA used after unprotected intercourse with the purpose to provide evidence that UPA, a new type of second-generation progesterone receptor modulator, represents a new evolutionary step in EC treatment.
emergency contraception; ulipristal acetate; levonorgestrel
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Achieving cost-neutrality with long-acting reversible contraceptive methods⋆
Trussell, James
Hassan, Fareen
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This analysis aimed to estimate the average annual cost of available reversible contraceptive methods in the United States. In line with literature suggesting long-acting reversible contraceptive (LARC) methods become increasingly cost-saving with extended duration of use, it aimed to also quantify minimum duration of use required for LARC methods to achieve cost-neutrality relative to other reversible contraceptive methods while taking into consideration discontinuation.
Study design
A three-state economic model was developed to estimate relative costs of no method (chance), four short-acting reversible (SARC) methods (oral contraceptive, ring, patch and injection) and three LARC methods [implant, copper intrauterine device (IUD) and levonorgestrel intrauterine system (LNG-IUS) 20 mcg/24 h (total content 52 mg)]. The analysis was conducted over a 5-year time horizon in 1000 women aged 20–29 years. Method-specific failure and discontinuation rates were based on published literature. Costs associated with drug acquisition, administration and failure (defined as an unintended pregnancy) were considered. Key model outputs were annual average cost per method and minimum duration of LARC method usage to achieve cost-savings compared to SARC methods.
The two least expensive methods were copper IUD ($304 per women, per year) and LNG-IUS 20 mcg/24 h ($308). Cost of SARC methods ranged between $432 (injection) and $730 (patch), per women, per year. A minimum of 2.1 years of LARC usage would result in cost-savings compared to SARC usage.
This analysis finds that even if LARC methods are not used for their full durations of efficacy, they become cost-saving relative to SARC methods within 3 years of use.
Previous economic arguments in support of using LARC methods have been criticized for not considering that LARC methods are not always used for their full duration of efficacy. This study calculated that cost-savings from LARC methods relative to SARC methods, with discontinuation rates considered, can be realized within 3 years.
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Hormonal contraceptive use and HIV disease progression among women in Uganda and Zimbabwe
Morrison, Charles S.
Chen, Pai-Lien
Nankya, Immaculate
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Ma, Yun-Rong
Chipato, Tsungai
Mugerwa, Roy
Dunbar, Megan
Arts, Eric
Salata, Robert A.
Journal of acquired immune deficiency syndromes (1999)
HIV-infected women need highly effective contraception to reduce unintended pregnancies and mother-to-child HIV transmission. Previous studies report conflicting results regarding the effect of hormonal contraception (HC) on HIV disease progression.
HIV-infected women in Uganda and Zimbabwe were recruited immediately after seroconversion; CD4 testing and clinical exams were conducted quarterly. The study endpoint was time to AIDS (two successive CD4 ≤200 cells/mm3 or WHO advanced stage 3 or stage 4 disease). We used marginal structural Cox survival models to estimate the effect of cumulative exposure to depot-medroxyprogesterone acetate (DMPA) and oral contraceptives (OC) on time to AIDS.
303 HIV-infected women contributed 1,408 person-years (py). 111 women (37%) developed AIDS. Cumulative probability of AIDS was 50% at 7 years and did not vary by country. AIDS incidence was 6.6, 9.3 and 8.8 per 100py for DMPA, OC and non-hormonal users. Neither DMPA (adjusted hazard ratio (AHR) = 0.90; 95% CI 0.76-1.08) nor OCs (AHR =1.07; 95% CI 0.89-1.29) were associated with HIV disease progression. Alternative exposure definitions of HC use during the year prior to AIDS or at time of HIV infection produced similar results. STI symptoms were associated with faster progression while young age at HIV infection (18-24 years) was associated with slower progression. Adding baseline CD4 level and setpoint viral load to models did not change the HC results but subtype D infection became associated with disease progression.
Hormonal contraceptive use was not associated with more rapid HIV disease progression but older age, STI symptoms and subtype D infection were.
HIV; disease progression; hormonal contraception; family planning; women
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