human immunodeficiency virus type-1 ( hiv-1 ) is well known to cause opportunistic infection ( oi ) and this is typically accompanied by declining levels of cd4 t - lymphocytes leading to impaired cell - mediated immunity . in the unusual case where a hiv-1 infected individual with a high cd4 cell count presents with recurrent infections , a clinician is faced with the possibility of a second underlying comorbidity . coinfection with a second retrovirus , human t lymphotropic virus type-1 ( htlv-1 ) , should also be considered , particularly in individuals of specific ethnic or geographic origins with a prevalence of greater than 1% in the general population . hiv-1 and htlv-1 infections have complex effects on adaptive immunity , with specific tropism for , but contrasting effects on cd4 t - cells . an estimated 10 to 20 million people worldwide are infected with htlv-1 with prevalence exceeding 1% in southern japan , central africa , and the caribbean . htlv-1 associated myelopathy ( ham ) occurs in 0.3% to 3% of carriers and the life - time risk of adult t cell leukemia / lymphoma ( atll ) is 1% to 5% . htlv-1 is also associated with a range of inflammatory diseases : ham , uveitis , pneumonitis , lymphocytic arthritis , and bronchiectasis . htlv-1 infection is also associated with a range of infections implying selective immune impairment , most notably disseminated strongyloides infection , norwegian scabies , infective dermatitis , bladder , and kidney infections . rhew et al 's review of the literature showed that being a carrier for htlv-1 was a risk factor for oi , particularly following the development of atll . there have been conflicting reports of the prevalence of htlv-1 and mycobacterium tuberculosis ( mtb ) coinfection in case  control studies carried out in geographical areas with high htlv-1 prevalence . a patient with hiv-1/htlv-1 coinfection presenting with an acquired immunodeficiency syndrome ( aids ) defining diagnosis of mycobacterium kansasii and pseudo - adult t - cell leukemia / lymphoma ( atll ) is presented . informed consent was obtained from the patient before all investigations and before publication of this case report . the patient , a 47-year - old west indian man was diagnosed with hiv-1 infection in the united kingdom in 2002 . he was heterosexual , had no history of injecting drug use and had a 20 pack year smoking history . he originally presented with recurrent cutaneous fungal infections , bacterial tonsillitis , varicella zoster infection , and oral candida . at diagnosis , his cd4 lymphocyte count was 757  cells / mm ( normal range [ nr ] 3001400 ) and hiv-1 viral load ( vl ) was 26,905  copies / ml . he remained clinically stable without antiretroviral therapy until 2010 when he presented with symptomatic anemia , night sweats , and a productive cough unresponsive to courses of antibiotics in the community . he had notable xeroderma , oral candida , obstructive airway chest wall movements , a peak expiratory flow rate of 300  l / minute ( predicted 580  l / minute ) , coarse widespread crepitations on auscultation and palpable hepatosplenomegaly . he had normal tone and power , brisk lower limb reflexes with down - going plantar responses , conserved sensation , and normal anal tone . salient laboratory findings were : erythrocyte sedimentation rate of 126  mm / hour ( nr 010  mm / hour ) , hemoglobin ( hb ) 7  g / dl ( nr 12.517.0 ) , mean cell volume 76.8 fl ( nr 83.0101.0 ) , ferritin 410  g / l ( nr 20300 ) , high performance liquid chromatography ( hplc ) showed hbc 67.8% ; hba2 4.6% ( nr 2.03.3% ) ; hbf 5.6% ( nr 01% ) . blood film showed anisopoikilocytosis , mature lymphocytosis with 14% atypical lymphocytes and no flower cells . serum b12 : 360  ng / l ( nr 160800 ) , red cell folate : 145.6  ng / ml ( nr 126480 ) , iron : 23  mol / l ( nr 929 ) , total iron binding capacity : 31  mol / l ( nr 4978 ) , transferrin saturation : 74 ( nr 2045% ) , pretransfusion reticulocyte count was 48.9    10 ( nr 28.186.1    10 ) , reticulocyte % : 1.6 ( 0.521.84% ) . a vasculitic screen was negative for anticyclic citrullinated peptide , antineutrophil cytoplasmic antibody , antinuclear antibody , and antiglomerular basement antibody . urinalysis revealed microscopic hematuria and proteinuria with a urine protein : creatinine ratio of 146 ( normal range < 20 ) . his estimated glomerular filtration rate was 79  ml / minute/1.73  m ( nr>59  ml / minute/1.73  m ) and computerized tomography of kidneys , ureters and bladder , flexible cystoscopy , renal , and prostate ultrasound were unremarkable . computerized tomography of the thorax revealed bilateral upper lobe bronchiectasis along with several ill - defined nodules , some with cavitation , and foci of consolidation in both the upper lobes , significant right middle lobe consolidation and associated volume loss ( figure 1 ) . bronchoalveolar lavage ( bal ) washings revealed an acute inflammatory response with no malignant cells . vl at this time was 4.62    10  copies / ml , absolute lymphocyte count 8000  cells / mm ( nr 11003600 ) and cd4 count 2239  cells / mm . ct thorax at the time of diagnosis of m. kansasii showing consolidation and bronchiectasis in upper lobes bilaterally . despite sputum culture conversion within 6 months of antimycobacterial therapy ( rifampicin , isoniazid , ethambutol ) , he remained symptomatic with weight loss , productive cough , and refractory anemia requiring multiple transfusions . hiv-1 vl was now 7.44    10  copies / ml , cd4 count 2477  cells / mm . at this point htlv-1 infection htlv-1 proviral load ( pvl ) was 42.9 deoxyribonucleic acid ( dna ) copies/100 peripheral blood mononuclear cells ( pbmcs ) . ninety - two percent of cd4 lymphocytes expressed cd25 ( nr 15.734.9 ) with no evidence of clonal t cell receptor ( tcr ) gene rearrangement . combination antiretroviral therapy ( cart ) was commenced in august 2011 with emtricitabine , etravirine , and darunavir / ritonavir ( a tenofovir sparing regimen was selected in light of his renal function ) . within 3 months the cd4 count decreased to 1495/mm htlv-1 pvl to 20.4% and hiv vl to 5098  copies / ml . cerebrospinal fluid ( csf ) obtained 4 months postinitiation of cart revealed 538  copies / ml csf ( paired plasma hiv vl 932  copies / ml ) and csf htlv-1 pvl of 41.8 % csf white cells ( paired pbmc pvl 28.2 % ) . after nine months on cart , hiv vl was undetectable in plasma , with decreases in htlv-1 pvl to 10.7% pbmcs and cd25 expression on cd4 cells to 87% . table 1 summarizes total lymphocyte , cd4 lymphocyte count , hiv-1 and htlv-1 vl before and in response to cart . total lymphocyte , cd4 lymphocyte count , human immunodeficiency virus-1 and human t - lymphotrophic virus type-1 viral load before and in response to combination antiretroviral therapy at htlv-1 diagnosis , htlv-1 unique integration site ( uis ) analysis by illumina high - throughput sequencing revealed a polyclonal distribution in which the largest clone contributed 1.77% of the total htlv-1 pvl . one year later , htlv-1 pvl 19% , the polyclonal distribution was similar and the same clone remained largest , contributing 0.96% of the total htlv-1 pvl ( figure 2 ) . each pie chart depicts the clonal abundance of unique integration sites using linker - mediated polymerase chain reaction ( pcr ) followed by high throughput sequencing . each slice of the pie chart represents the relative abundance of an individual clone within that sample . precombined antiretroviral therapy ( cart ) , the relative abundance of the largest clone ( blue ) represents 1.77% of the pvl ( 76.3/10,000 peripheral blood mononuclear cells ( pbmc ) ) and following 1 year of cart reduces to 0.96% of pvl ( 18.3/10,000 pbmc ) . at htlv-1 diagnosis , the majority of cd4 t cells , as determined by flow cytometry , were effector memory cells ( tem , cd45raccr794.9% ) . one year later , there was reduction in both absolute and relative frequency of cd4 tem cells but no change in immunophenotype . this case caused diagnostic uncertainty since the absolute lymphocyte count , htlv-1 serology and % atypical lymphocytes fulfilled shimoyama criteria for the diagnosis of chronic atll . however , there was no evidence of clonal t - cell proliferation by tcr gene rearrangement studies nor of monoclonal htlv-1 integration by high - throughput sequencing . htlv-1 infection results in increased t lymphocyte proliferation , which is usually balanced by a higher rate of infected cell death due to immune surveillance . total lymphocyte , cd4 and cd8 t lymphocyte subsets are usually within the normal range in htlv-1 mono - infection . unlike hiv-1 infection in which viremia is maintained by infectious spread , htlv-1 pvl , in chronic infection is thought to be substantially maintained by proliferation of infected cells and htlv-1 integration site analysis reveals multiple clonal expansions of cd4 t lymphocytes . the very high hiv-1 viremia , despite the chronicity of infection , may reflect the abnormally high cd4 cell count due to htlv-1 infection , similar to that seen in infants and young children . this patient had lymphocytosis predominantly due to an increased frequency of activated cd4ccr4 tem cells . it has been suggested that active hiv infection increases ccr4 t - cells via secretion of the ccr4 ligands tarc and mdc by activated monocyte / macrophages . we postulate that the coinfection with the 2 viruses led to overproduction of poorly functional lymphocytes whilst providing an environment for high levels of hiv virion production . it is possible that cd4t - lymphocytes were coinfected with the 2 viruses , but we have not been able to demonstrate this . if , despite the high cd4 cell count , hiv-1 was contributing to high cd4 lymphocyte turnover , treatment of hiv-1 with cart might be expected to further increase the cd4 cell count , unmasking the true degree of htlv-1 related cd4 t lymphocyte proliferation . data from beilke et al suggest that where individuals with hiv / htlv-1 coinfection have high htlv-1 vl , cart has limited efficacy in controlling htlv-1 viremia . however , in this subject cart , which was hiv-1 specific , was associated with normalization of cd4 counts and a significant decrease in the proportion of pbmcs infected with htlv-1 . whilst zidovudine with lamivudine has not impacted on htlv-1 vl in patients with ham , zidovudine in combination with interferon-2a has improved the outcome in atll . raltegravir has been shown to prevent htlv-1 infection in vitro . in baboons infected with simian ( s ) tlv-1 , treatment with sodium valproate , combined with zidovudine , resulted in significant , sustained reduction in stlv-1 vl . raltegravir may be a suitable alternative , since the role of art combined with histone deacetylase inhibition is to prevent an initial increase in htlv-1 viral replication associated with increased htlv-1 transcription . the anti - htlv-1 efficacy of zidovudine , raltegravir , and histone deacetylase inhibitors requires further clinical evaluation and may only impact on continuing infectious spread . the normalization of the cd4 cell count , with a paradoxical decrease in cd4 count during hiv - specific cart , suggested proliferation of htlv-1-infected cd4 t - cells driven by hiv - related immune activation ; this interpretation was supported by the observation of polyclonal htlv-1 integration at both time points . in conclusion , we present a case of pseudo - atll in a hiv-1 infected individual whose high cd4 counts were deceptive as he was significantly immunosuppressed . paradoxically , there was a significant improvement of cd4 lymphocytosis and htlv-1 vl post commencement of hiv-1 specific cart . we postulate that mutually beneficial interplay between hiv-1 and htlv-1 maintained high loads of each virus , and proliferation of poorly functional cd4 cells despite chronic infection . we suggest that the likely mechanism was immune activation of t - cells , which was attenuated by hiv-1 virological control with cart .
abstracthuman immunodeficiency virus type-1 ( hiv-1 ) and human t lymphotropic virus type-1 ( htlv-1 ) infections have complex effects on adaptive immunity , with specific tropism for , but contrasting effects on , cd4 t lymphocytes : depletion with hiv-1 , proliferation with htlv-1 . impaired t lymphocyte function occurs early in hiv-1 infection but opportunistic infections ( ois ) rarely occur in the absence of cd4 lymphopenia . in the unusual case where a hiv-1 infected individual with a high cd4 count presents with recurrent ois , a clinician is faced with the possibility of a second underlying comorbidity.we present a case of pseudo - adult t cell leukemia / lymphoma ( atll ) in hiv-1/htlv-1 coinfection where the individual fulfilled shimoyama criteria for chronic atll and had pulmonary mycobacterium kansasii , despite a high cd4 lymphocyte count . however , there was no evidence of clonal t - cell proliferation by t - cell receptor gene rearrangement studies nor of monoclonal htlv-1 integration by high - throughput sequencing . 
 mutually beneficial interplay between hiv-1 and htlv-1 , maintaining high level hiv-1 and htlv-1 viremia and proliferation of poorly functional cd4 cells despite chronicity of infection is a postulated mechanism.despite good microbiological response to antimycobacterial therapy , the patient remained systemically unwell with refractory anemia . 
 subsequent initiation of combined antiretroviral therapy led to paradoxical resolution of cd4 t lymphocytosis as well as hiv-1 viral suppression and decreased htlv-1 proviral load . 
 this is proposed to be the result of attenuation of immune activation post - hiv virological control.this case illustrates the importance of screening for htlv-1 in hiv-1 patients with appropriate clinical presentation and epidemiological risk factors and explores mechanisms for the complex interactions on hiv-1/htlv-1 adaptive immunity .