HIV Disease Medication
- Author: Nicholas John Bennett, MB, BCh, PhD; Chief Editor: Ronald A Greenfield, MD more...
Medication Summary
Effective antiretroviral therapy is the most important intervention in terms of improving longevity and preventing opportunistic infections in patients with human immunodeficiency virus (HIV) infection. Therapy should involve combinations of drugs—two nucleoside-analogue reverse-transcriptase inhibitors combined with either a protease inhibitor or a non-nucleoside–analogue reverse-transcriptase inhibitor.[76, 109] Antiretroviral drug classes and agents within each class are listed in Table 1, below (see individual medication tables for more detail).
As of May 2011, a total of 26 antiretroviral drugs have been approved for use in HIV-infected adults and adolescents; 14 of these have an approved pediatric treatment indication and 13 are available as a pediatric formulation or capsule size. Of the 26 antiretroviral drugs that have been approved, 3 are no longer being manufactured either because of the development of improved formulations (ie, amprenavir replaced by fosamprenavir) or because of limited use (ie, delavirdine and zalcitabine [ddC]).
Table 1. Antiretroviral Drug Classes and Agents (Open Table in a new window)
| Nucleoside reverse transcriptase inhibitors (NRTIs) | Abacavir (Ziagen, ABC) Didanosine (Videx, Videx EC, ddI) Emtricitabine (Emtriva, FTC) Lamivudine (Epivir, 3TC) Stavudine (Zerit, Zerit XR, d4T) Tenofovir DF (Viread, TDF) Zalcitabine (Hivid, ddC)* Zidovudine (Retrovir, ZDV, AZT) |
| Protease inhibitors (PIs) | Amprenavir (Agenerase, AVP)* Atazanavir (Reyataz , ATV) Darunavir (Prezista, DRV) Fosamprenavir (Lexiva, f-APV) Indinavir (Crixivan, IDV) Lopinavir and ritonavir (Kaletra, LPV/r) Nelfinavir (Viracept, NFV) Ritonavir (Norvir, RTV) Saquinavir (Invirase [hard gel] capsule, SQV) Tipranavir (Aptivus, TPV) |
| Non-nucleoside reverse transcriptase inhibitors (NNRTIs) | Delavirdine (Rescriptor, DLV) Efavirenz (Sustiva, EFV) Etravirine (Intelence, ETR) Nevirapine (Viramune, NVP) Rilpivirine (Edurant) |
| Fusion inhibitors | Enfuvirtide (Fuzeon, T-20) |
| Cellular chemokine receptor (CCR5) antagonists | Maraviroc (Selzentry, MVC) |
| Integrase inhibitors | Raltegravir (Isentress, RAL) |
| *No longer available on market | |
Combination therapy has been shown to dramatically reduce the likelihood of drug resistance (many drug-resistant mutations are mutually exclusive) and to suppress viral replication to the point that progression to AIDS is significantly slowed. Antiviral-resistance mutations often affect more than one drug simultaneously because of similar development pipelines and the ultimate molecular structure of the drug, and combination choices should account for this possibility.
Ritonavir, a protease inhibitor that may be used in its own right, boosts blood levels of other protease inhibitors. This permits a reduced dosage of the coadministered drug. Various products have been formulated to include PIs combined with ritonavir.
Numerous antiretroviral combination products are available on the market to assist patients with compliance and decrease the daily number of tablets and capsules required (see Table 2, below).
Table 2. Antiretroviral Combination Products (Open Table in a new window)
| Drug Content per Tablet/Capsule* | Brand Name | Adult Dose (≥40 kg) |
| Abacavir 600 mg Lamivudine 300 mg | Epzicom | 1 tab PO qd |
| Abacavir 300 mg Lamivudine 150 mg Zidovudine 300 mg | Trizivir | 1 tab PO bid |
| Efavirenz 600 mg Emtricitabine 200 mg Tenofovir DF 300 mg | Atripla | 1 tab PO qd on empty stomach |
| Emtricitabine 200 mg Rilpivirine 25 mg Tenofovir DF 300 mg | Complera | 1 tab PO qd with a meal |
| Emtricitabine 200 mg Tenofovir DF 300 mg | Truvada | 1 tab PO qd CrCl 30-49 mL/min: 1 tab PO q48h CrCl < 30 mL/min: Do not administer |
| Lamivudine 150 mg Zidovudine 300 mg | Combivir | 1 tab PO bid |
| *Not indicated for patients requiring dosage adjustments (eg, weight < 40 kg, renal impairment, hepatic impairment, dose-limiting adverse effects) unless otherwise stated. | ||
Antiretroviral agent, nucleoside reverse-transcriptase inhibitor
Class Summary
NRTIs agents inhibit viral replication by inhibiting viral RNA–dependent DNA polymerase.
Abacavir (Ziagen)
This NRTI interferes with HIV viral RNA–dependent DNA polymerase and inhibits viral replication. In its 2011 guidelines, the Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection recommends screening for HLA-B*5701 before starting patients on a regimen that contains abacavir, to reduce the risk of hypersensitivity reaction.[76]
Didanosine (Videx, Videx EC)
Didanosine interferes with HIV viral RNA–dependent DNA polymerase and inhibits viral replication.
Emtricitabine (Emtriva)
This agent is a synthetic nucleoside cytosine analog classified as an NRTI. It competes with deoxycytidine-5'-triphosphate and incorporates into viral DNA, causing chain termination.
Lamivudine (Epivir)
Lamivudine is a thymidine analog that inhibits viral replication.
Stavudine (Zerit, Zerit XR)
Stavudine competes with deoxycytidine-5'-triphosphate and incorporates into viral DNA, causing chain termination.
Tenofovir disoproxil fumarate (Viread)
This agent inhibits the activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, by DNA chain termination. It is administered as the prodrug bis-isopropoxycarbonyloxymethyl ester derivative of tenofovir, which is converted, through various enzymatic processes, to tenofovir, a nucleotide analog of adenosine 5'-monophosphate. Bioavailability is enhanced by a high-fat meal. Prolonged intracellular distribution allows for once-daily dosing.
Zidovudine (Retrovir)
Zidovudine is a thymidine analog that inhibits viral replication.
Antiretroviral Agent, Protease Inhibitor
Class Summary
PIs inhibit protein precursors necessary for HIV infection of uninfected cells.
Atazanavir (Reyataz)
An azapeptide HIV-1 PI, atazanavir prevents virion maturation by selectively inhibiting Gag and Gag-Pol polyproteins in HIV-1–infected cells.
Darunavir (Prezista)
This HIV-1 PI selectively inhibits HIV-encoded Gag-Pol polyprotein cleavage in infected cells, thereby preventing mature virus particle formation. It is indicated for HIV disease that has not responded to treatment with other antiretroviral agents. Coadminister with low-dose ritonavir (ritonavir-boosted therapy decreases elimination and increases darunavir serum concentration).
Darunavir is typically coadministered with other anti-HIV agents (eg, NRTIs). Food increases maximum plasma concentration (Cmax) and area under the curve (AUC). This agent is indicated for HIV infection in antiretroviral treatment–experienced adults (eg, those with HIV-1 strains resistant to more than one PI).
Fosamprenavir (Lexiva)
Fosamprenavir is a prodrug that is converted to amprenavir by cellular phosphatases in vivo.
Lopinavir and ritonavir (Kaletra)
Lopinavir inhibits HIV protease and renders the enzyme incapable of processing polyprotein precursor, leading to production of noninfectious immature HIV particles. Ritonavir inhibits CYP3A metabolism of lopinavir, increasing plasma levels of lopinavir.
Nelfinavir (Viracept)
Nelfinavir inhibits HIV-1 protease, resulting in the production of an immature and noninfectious virus.
Indinavir (Crixivan)
Indinavir prevents formation of protein precursors necessary for HIV infection of uninfected cells and viral replication.
Ritonavir (Norvir)
This HIV PI is used as a part of double or triple therapy with nucleosides and other protease inhibitors.
Saquinavir (Invirase)
Saquinavir inhibits HIV protease and renders the enzyme incapable of processing polyprotein precursor, leading to production of noninfectious immature HIV particles.
Tipranavir (Aptivus)
A nonpeptidic PI that inhibits HIV replication. Indicated for combination antiretroviral treatment in adults with HIV-1 infection who have evidence of viral replication and who are highly experienced with treatment or who have HIV-1 strains that are resistant to multiple PIs.
Tipranavir must be coadministered with ritonavir (200 mg) to attain therapeutic levels (ie, tipranavir/ritonavir). Administration alone, without ritonavir-boosted levels, is not effective. Genotypic or phenotypic testing and/or treatment history should guide use.
Antiretroviral agent, non-nucleoside reverse-transcriptase inhibitor
Class Summary
NNRTIs inhibit viral replication.
Delavirdine (Rescriptor)
An NNRTI of HIV-1, delavirdine directly binds to reverse transcriptase and inhibits RNA- and DNA-dependent DNA polymerase.
Efavirenz (Sustiva)
Efavirenz is an NNRTI with activity against HIV-1. This agent binds to reverse transcriptase and blocks RNA-dependent and DNA-dependent DNA polymerase activities, including HIV-1 replication. Efavirenz does not require intracellular phosphorylation for antiviral activity.
Etravirine (Intelence)
Etravirine is an NNRTI of HIV-1 that binds directly to reverse transcriptase, causing catalytic site disruption. This action blocks RNA- and DNA-dependent DNA polymerase activities. Etravirine does not inhibit human DNA polymerases alpha, beta, or gamma.
This agent is indicated for use in combination with other antiretroviral agents for treatment-experienced HIV-infected adults who have viral replication and HIV-1 strains resistant to NNRTIs and other antiretroviral agents. If virologic failure was experienced with other NNRTIs, do not use etravirine in combination with NRTIs only.
Nevirapine (Viramune)
Nevirapine is an NNRTI that limits virus replication by a mechanism different from the nucleosidase inhibitors such as zidovudine and lamivudine.
Rilpivirine (Edurant)
Rilpivirine is a NNRTI that inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase. It does not inhibit the human cellular DNA polymerases alpha, beta, and gamma.
Antiretroviral Agent, Integrase Inhibitor
Class Summary
This agent prevents insertion of a DNA copy of the viral genome into host cell DNA. It is indicated for HIV-1 infection combination therapy in treatment-experienced adults with evidence of viral replication and drug-resistant HIV-1 strains.
Raltegravir (Isentress)
Raltegravir is the first available agent in the class of integrase strand transfer inhibitors.
Antiretroviral Agent, Fusion Inhibitor
Class Summary
These agents disrupt the ability of HIV to fuse with and infect healthy T cells.
Enfuvirtide (Fuzeon)
This is the first agent in the new anti-HIV class called fusion inhibitors. Indicated for use in combination with other antiretroviral agents for HIV-1 infection in treatment-experienced patients who demonstrate evidence of HIV-1 replication despite ongoing antiretroviral therapy.
Enfuvirtide binds to HIV gp41 surface protein, thereby, disrupting the virus's ability to fuse with and infect healthy T cells. In clinical trials, subjects were twice as likely to achieve undetectable HIV-1 plasma levels (eg, < 40 copies/mL) when enfuvirtide was added to antiretroviral optimized regimens than without enfuvirtide added to therapy.
Antiretroviral agent, CCR5 antagonist
Class Summary
These agents block viral entry into white blood cells via the CCR5 co-receptor.
Maraviroc (Selzentry)
Maraviroc blocks viral entry via the CCR5 co-receptor into WBCs, reduces viral load, and increases T-cell counts in infection with CCR5-tropic HIV-1 (ie, R5 virus). Accelerated approval by the US Food and Drug Administration (FDA) was based on 24-wk data. This agent is indicated for combination treatment with optimized background therapy in treatment-experienced adults infected with only R5 virus who have evidence of viral replication and have HIV-1 strains resistant to multiple antiretroviral agents.
Antiretroviral Combinations
Class Summary
Combination products are valuable to patient care and help ensure compliance.
Abacavir, lamivudine, zidovudine (Trizivir)
Abacavir is a nucleoside reverse transcriptase inhibitor, which interferes with HIV viral RNA dependent DNA polymerase and inhibits viral replication. Lamivudine and zidovudine are thymidine analogs that inhibit viral replication.
Abacavir/lamivudine (Epzicom)
NRTI combination product.
Efavirenz/emtricitabine/tenofovir (Atripla)
NRTI and NNRTI combination product.
Emtricitabine/rilpivirine/tenofovir (Complera)
NRTI and NNRTI combination product.
Emtricitabine/tenofovir (Truvada)
NRTI combination product.
Lamivudine/zidovudine (Combivir)
NRTI combination product.
Antibiotic, Sulfonamide Derivative
Class Summary
Therapy should cover all likely pathogens in this clinical setting.
Sulfamethoxazole and Trimethoprim (Bactrim, Bactrim DS, Septra, Septra DS, Sulfatrim)
This combination inhibits bacterial synthesis of dihydrofolic acid by competing with paraaminobenzoic acid. This results in inhibition of bacterial growth.
Growth hormone releasing factor
Class Summary
This agent decreases visceral adipose tissue.
Tesamorelin (Egrifta)
Tesamorelin is a growth hormone–releasing factor (GRF) analog indicated for reduction of excess abdominal fat in patients with HIV-associated lipodystrophy. This agent stimulates growth hormone production and increases serum levels of insulin-like growth factor–1 (IGF-1). It elicits anabolic and lipolytic actions.
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| Nucleoside reverse transcriptase inhibitors (NRTIs) | Abacavir (Ziagen, ABC) Didanosine (Videx, Videx EC, ddI) Emtricitabine (Emtriva, FTC) Lamivudine (Epivir, 3TC) Stavudine (Zerit, Zerit XR, d4T) Tenofovir DF (Viread, TDF) Zalcitabine (Hivid, ddC)* Zidovudine (Retrovir, ZDV, AZT) |
| Protease inhibitors (PIs) | Amprenavir (Agenerase, AVP)* Atazanavir (Reyataz , ATV) Darunavir (Prezista, DRV) Fosamprenavir (Lexiva, f-APV) Indinavir (Crixivan, IDV) Lopinavir and ritonavir (Kaletra, LPV/r) Nelfinavir (Viracept, NFV) Ritonavir (Norvir, RTV) Saquinavir (Invirase [hard gel] capsule, SQV) Tipranavir (Aptivus, TPV) |
| Non-nucleoside reverse transcriptase inhibitors (NNRTIs) | Delavirdine (Rescriptor, DLV) Efavirenz (Sustiva, EFV) Etravirine (Intelence, ETR) Nevirapine (Viramune, NVP) Rilpivirine (Edurant) |
| Fusion inhibitors | Enfuvirtide (Fuzeon, T-20) |
| Cellular chemokine receptor (CCR5) antagonists | Maraviroc (Selzentry, MVC) |
| Integrase inhibitors | Raltegravir (Isentress, RAL) |
| *No longer available on market | |
| Drug Content per Tablet/Capsule* | Brand Name | Adult Dose (≥40 kg) |
| Abacavir 600 mg Lamivudine 300 mg | Epzicom | 1 tab PO qd |
| Abacavir 300 mg Lamivudine 150 mg Zidovudine 300 mg | Trizivir | 1 tab PO bid |
| Efavirenz 600 mg Emtricitabine 200 mg Tenofovir DF 300 mg | Atripla | 1 tab PO qd on empty stomach |
| Emtricitabine 200 mg Rilpivirine 25 mg Tenofovir DF 300 mg | Complera | 1 tab PO qd with a meal |
| Emtricitabine 200 mg Tenofovir DF 300 mg | Truvada | 1 tab PO qd CrCl 30-49 mL/min: 1 tab PO q48h CrCl < 30 mL/min: Do not administer |
| Lamivudine 150 mg Zidovudine 300 mg | Combivir | 1 tab PO bid |
| *Not indicated for patients requiring dosage adjustments (eg, weight < 40 kg, renal impairment, hepatic impairment, dose-limiting adverse effects) unless otherwise stated. | ||
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