• Antiretroviral drugs
    • nucleoside reverse transcriptase inhibitors (NRTIs)
      • act by competitively inhibiting HIV-encoded RNA-dependent DNA polymerase (reverse transcriptase)
      • cause chain termination that decreases viral DNA synthesis and virus replication.
      • They prevent infection but do not clear cells already infected.
      • must first undergo intracellular phosphorylation to be active.
      • Zidovudine(AZT)
        • a pyrimidine analogue
        • adverse effects of zidovudine,
          • headache, diarrhea, and fever
          • dose-limiting toxicitiesare granulocytopenia and anemia.
        • reduces the rate of progression of HIV.
        • When given to pregnant women starting in the second trimester, then during labor, and then to the newborn, the vertical transmission of HIV is reduced by up to 25%.
        • This agent is also used for postexposure prophylaxis.
      • Didanosine(ddI)
        • Purine analogue
        • Requires administration on an empty stomach.
        • Dose limiting toxicities
          • Pancreatitis
          • sensory peripheral neuropathy
          • optic neuritis.
      • Stavudine
        • thymidine nucleoside analogue
        • Except for acid lability, stavudine, a, is similar to didanosinein pharmacokinetics, therapeutic use, and adverse effects that typically resolved with discontinuation.
      • Zalcitabine(ddC)
        • also cause chain termination of viral DNA elongation.
        • Reversible peripheral neuropathymay limit the use of this agent in 30% of patients.
      • Lamivudine(3TC),emtricitabine ,abacavir(ABC)
        • Lamivudine
          • a cytosine analogue
          • Side effects include headache and GI upset
        • Emtricitabine
          • a fluorinated analog of lamivudine with a long half-life
          • allows for once-daily dosing.
        • Abacavir
          • a guanosine analogue
          • Occasional fatal hypersensitivity reactions
        • Tenofovir (TDF)
          • an analogue of adenosine
          • This agent is more convenient than older antiretroviral agents in that it has a once-daily dosing schedule.
          • Most common side effects are GI.
    • Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
      • NNRTIs act similarly to NRTIs
      • These agents do not require phosphorylationfor their activity
      • Nevirapine (NVP)
        • Nevirapine is used in combination regimens
        • It has also recently been shown to reduce vertical transmission of HIV from mother to newborn when used as monotherapy (MCQ)
        • Adverse effects
          • Steven-Johnson syndrometoxic epidermal necrolysis
          • hepatotoxicity.
        • Drug interactions
          • Concurrent use of nevirapine and ketoconazole
            • increase plasma levels of the nevirapine, while decreasing levels of the ketoconazole due to nevirapine induces CYP3A
          • The levels of the drug are reduced when coadministered with rifampin.
      • Delavirdine(DLV),Efavirenz(EFV)
        • Delavirdine
          • Side effects ofDLVinclude rash and GI upset
          • drug is metabolized by CYP3A system.
          • Drug interaction should be monitored.
        • Efavirenz(EFV)
          • dosed once daily
          • is also metabolized by CYP3A
          • Main side effects of this agent are dizziness, insomnia, confusion, amnesia, nightmares, and other CNS effects (MCQ)
          • These are observed in up to 50% of patients and usually abate with time.


    • HIV-1 protease inhibitors
      • competitively inhibit viral-induced Gag-Pol polyprotein cleavage by HIV-1 protease, a step necessary for virion maturation
      • leads to clearance of the immature virion.
      • used in combination with nucleoside analogues to delay and possibly
      • reverse the clinical progression of AIDS.
      • frequently associated with development of lipodystrophy  (MCQ)
      • have significant drug interactions due to inhibition of CYP3A4.
      • Resistance due to changes in the protease gene has been described
      • Resistance is more common when
        • patients are noncompliant
        • patients take drug ‘‘holidays’’
        • when inhibitors are used as monotherapy
        • given at subtherapeutic doses.
      • Saquinavir
        • bioavailability of this agent is reduced by other drugs that increase liver microsomal enzyme activity
        • it is increased by drugs that inhibit enzyme activity.
        • Saquinavir is well tolerated,
        • because of its limited bioavailabilitydue to extensive first-pass metabolism, it has only a modest effect
        • For greater efficacy, it is often co-administered with ritonavir, a protease inhibitor
        • The most common adverse effects include GI disturbances and rash.
      • Ritonavir
        • Close monitoring of other agents patients are using is recommended.
        • Ritonavir is extensively inhibits many liver cytochrome P 450 enzymes
        • leading to accumulation of many drugs that are metabolized by this system (including saquinavir).
        • It also induces some forms of cytochrome P-450 enzymes, leading to reduced bioavailability of other drugs.
        • adverse effect profile
          • moderate GI disturbances, headache, fatigue
          • taste disturbances, and perioral paresthesia.
      • Lopinavir–ritonavir
        • combination is shown to enhance efficacy of both drugs while reducing toxicity.
      • Indinavir
        • Like ritonavir, it interferes with liver microsomal enzyme metabolism, but not to the same extent, and it inhibits the metabolism of some drugs and vice versa.
        • Indinavir is well tolerated
        • Mild GI symptoms
        • reversible nephrolithiasiscan develop  (MCQ)
          • due to precipitation in the renal collecting duct system
          • can be prevented with attention to hydration
        • Indirect hyperbilirubinemiais also common. (MCQ)
      • Nelfinavir,Amprenavir,Fosamprenavir
        • These agents exhibit drug interactions similar to those of indinavir.
        • Moderate diarrhea and fatigue have been reported.
        • Amprenavirmay cause severe rashes
          • it is usually coadministered with ritonavir.
        • Fosamprenavir
          • a prodrug of amprenavir
          • allows for reduced daily dosing.
      • Atazanavir
        • Common adverse effects GI disturbances and indirect hyperbilirubinemia with jaundice.
        • Atazanavir, like other PIs, inhibits CYP3A4 and CYP 2C9with a great likelihood of drug– drug interactions.
      • Tipranavir
        • bioavailability is increased with a high-fat meal (MCQ)
        • undergoes extensive first-pass metabolism
        • therefore, is co-administered with ritonavir.
        • Its most common adverse effects are GI disturbances and rash(it contains a sulfonamide moiety).
        • Its use is also associated with development of hepatic dysfunction (black box warning).
    • Anti-HIV agents—fusion inhibitors.
      • Enfuvirtide
        • blocks entry of virus into the cell by binding to viral gp41 glycoprotein
        • This drug is administered subcutaneously,
        • injection site reactions being the most common side effect.
        • It is used in combination therapies.
    • Highly active antiretroviral therapy (HAART)
      • usually 3–4 agents from several different classes, that are used in treatment of HIV/AIDS to prevent development of resistance.

HAART: Highle Active Anti-Retroviral Therapy for HIV

On stopping ARVs, HAART, Atripla, “HIV Meds”

Antiretroviral Therapy in HIV

Highly active antiretroviral treatment HAART

Surveillance of transmitted ARV drug resistance among HIV-1 infected women

Mortality and causes of death among women living with HIV

Drugs and HIV Evolution

Possible Alt Treatments for HIV

With Antiretroviral Drugs (ARVs), Does HIV Still Matter?

HIV Infection and Cardiovascular Health