<prompt> The drug efavirenz inhibits:HIV proteaseHIV reverse transcriptaseHIV integraseHIV entry-into the cell  <response>: Ans. b. HIV reverse transcriptase Ref: Katzung 12e p870; Goodman Gilman 12e p1626The drug efavirenz inhibits HIV reverse transcriptase.NNRTIs Efavirenz bind to HIV-1 reverse transcriptase at a different site than NRTIs and induces a conformational change in the enzyme and disrupts catalytic activity.Non-Nucleoside Reverse Transcriptase Inhibitor NNRTINNRTIs bind to HIV-1 reverse transcriptase at a different site than NRTIs and induces a conformational change in the enzyme and disrupts catalytic activityWell absorbed from GIT; bioavailability increased with a high fat mealPlasma-protein binding: 99; Poor penetration into blood brain barrierMetabolized by oxidation by CYP2D6 and CYP3A4All NNRTIs are specific for HIV-1 with no action against HIV-2Saquinavir is a protease inhibitor.Saquinavir, the first approved HIV protease inhibitor, is a peptidomimetic hydroxyethylamine--Goodman Gillman 12e p1648Anti-Retroviral TherapyThere are five classes of drugs, which are usually used in combination, to treat HIV infection.Use of these drugs in combination can be termed anti-retroviral therapy ART, combination anti-retroviral therapy cART or highly active anti-retroviral therapy HAARTAnti-retroviral ARV drugs are broadly classified by the phase of the retrovirus life cycle that the drug inhibits.Typical combinations include 2 NRTIs as a backbone along with 1 NNRTI, PI or I as a base.Name of GroupExamplesMechanismEntry inhibitor Fusion inhibitorsMaravirocQEnfuvirtideQ Interfere with binding, fusion entry of HIV- 1 to host cell by blocking a target. Maraviroc works by targeting CCR5, a co-receptor located on human helper T-cellsNucleoside Reverse Transcriptase Inhibitors NRTI Nucleotide Reverse Transcriptase Inhibitors NtRTIZidovudine, Abacavir, La- mivudine, Emtricitabine Tenofovir NtRTI Nucleoside nucleotide analogues which inhibit reverse transcription Both act as competitive substrate inhibitorsNon-Nucleoside reverse transcriptase inhibitors NNRTI1st generation: Nevirapine EfavirenzQ2nd generation: Etravirine RilpivirineQ Inhibit reverse transcriptase by binding to an allosteric site of the enzyme NNRTIs act as non-competitive inhibitors of reverse transcriptase. HIV-2 is naturally resistant to NNRTIs.Integrase inhibitors Integrase Nuclear Strand Transfer Inhibitors or IsRaltegravirQElvitegravirQDolutegravirQ Inhibit the viral enzyme integrase. which is responsible for integration of viral DNA into the DNA of the infection cell.Protease inhibitorsLopinavir, Indinavir, Nelfinavir, Ritonavir, Amprenavir; Daruna- vir Atazanavir 1st line Block the viral protease enzyme necessary to produce mature virions upon budding from the host membrane. 