HIV Infection and AIDS Medication

Updated: Dec 05, 2017
  • Author: Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP; Chief Editor: Michael Stuart Bronze, MD  more...
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Medication

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 recommended by current guidelines. Recommendations are specific for various patient groups (eg, treatment naïve, treatment experienced, coinfection with hepatitis C). [5] Antiretroviral drug classes and agents within each class are listed in Table 1, below (see individual medication tables for more detail).

Many of the antiretroviral drugs that have been approved for HIV-infected adults and adolescents are gaining FDA approval for use in younger children. For more information, see Pediatric HIV Infection.

Of the antiretroviral drugs that have been approved, several 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]).

Several combination products that contain tenofovir alafenamide (TAF) are now approved in the United States. TAF is a more targeted form of tenofovir that has demonstrated high antiviral efficacy at a dose that is 10 times lower than that of tenofovir DF, as well as an improved renal and bone safety profile.

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)



Tenofovir AF (TAF)



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)



Dolutegravir (Tivicay, DTG)



Elvitegravir (Vitekta, EVG)



*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 PI that may be used in its own right, boosts blood levels of other PIs. This permits a reduced dosage of the coadministered drug. Various products have been formulated to include PIs combined with ritonavir.

Combination products

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)
Dolutegravir 50 mg



Rilpivirine 25 mg



Juluca 1 tab PO qd with a meal
Elvitegravir 150 mg



Cobicistat 150 mg



Emtricitabine 200 mg



Tenofovir AF 10 mg



Genvoya 1 tab PO qd
Elvitegravir 150 mg



Cobicistat 150 mg



Emtricitabine 200 mg



Tenofovir DF 300 mg



Stribild 1 tab PO qd
Abacavir 600 mg



Lamivudine 300 mg



Epzicom 1 tab PO qd
Abacavir 600 mg



Dolutegravir 50 mg



Lamivudine 300 mg



Triumeq 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



Rilpivirine 25 mg



Tenofovir AF 25 mg



Odefsey 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



Emtricitabine 200 mg



Tenofovir AF 300 mg



Descovy 1 tab PO qd



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.

A subgroup analysis of black patients with HIV enrolled in the 48-week, open-label SPIRIT (Switching PI to Rilpivirine In-combination with Truvada) trial showed that switching from an antiretroviral regimen consisting of a boosted PI and ritonavir (RTV) plus 2 nucleoside/nucleotide reverse-transcriptase inhibitors (PI+RTV+2NRTIs) to a simplified once-daily, single-tablet regimen of rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF) is safe and effective in this population. [155, 156]

Patients were randomized to undergo an immediate switch to RPV/FTC/TDF at baseline or to maintain their PI+RTV+2NRTIs regimen for 24 weeks and then switch to RPV/FTC/TDF for 24 weeks (delayed switch).

At 24 weeks, a subgroup analysis of black patients in the study showed that viral suppression rates (HIV-1 RNA < 50 copies/mL) were 95% in the RPV/FTC/TDF group and 91% in the group receiving PI+RTV+2NRTIs; ie, no significant difference existed. At 48 weeks, 89% of black patients in the immediate-switch group maintained viral suppression, compared with 95% of those in the delayed-switch group, which again was not considered a significant difference. [155, 156]

At 48 weeks, when all patients in the study were taken into account, there was no significant difference in viral suppression between the immediate-switch (89%) and delayed-switch (92%) groups; the rates of adverse events were similar in both groups as well. [155, 156] However, investigators noted significant improvement in lipid levels in patients who received the single-tablet RPV/FTC/TDF regimen. [156]

The FDA has approved a once-daily, fixed-dose triple-combination pill (Triumeq) containing the antivirals dolutegravir, abacavir, and lamivudine for the treatment of patients aged 18 years or older with HIV infection. The FDA based its approval primarily on the results of 2 studies, in one of which, a 96-week study in treatment-naive adults, virologic suppression occurred in 80% of patients receiving dolutegravir and abacavir/lamivudine (administered separately), compared with 72% of patients taking a single-pill regimen of efavirenz, emtricitabine, and tenofovir (Atripla). [157]

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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. [6]

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.

This drug has shown substantial efficacy and safety in PReP trials with IV drug users and heterosexually active adults. CDC guidelines recommend tenofovir alone as an alternative regimen to emtricitabine/tenofovir for these populations, but not for MSM, among whom its efficacy has not been studied.

Zidovudine (Retrovir)

Zidovudine is a thymidine analog that inhibits viral replication.

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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.

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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.

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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 was the first available agent in the class of integrase strand transfer inhibitors.

Dolutegravir (Tivicay)

Dolutegravir is an integrase strand transfer inhibitor (INSTI) that inhibits catalytic activity of HIV-1 integrase, an HIV encoded enzyme required for viral replication. It is approved for use in children 12 years or older who weigh at least 40 kg.

Elvitegravir (Vitekta)

Integrase inhibitor that is used in combination with an HIV protease inhibitor (ie, atazanavir, lopinavir, darunavir, fosamprenavir, or tipranavir) and coadministered with ritonavir plus other antiretroviral drug(s) as indicated for the treatment of HIV-1 infection in antiretroviral treatment-experienced adults. It was originally approved as part of the combination product elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild).

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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.

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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.

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Complete Regimen Combinations

Class Summary

Complete fixed-dose regimens assist with medication adherence. Two-, three-, and four-drug combination products are available to decrease pill burden and administration frequency.

Dolutegravir/rilpivirine (Juluca)

First 2-drug, fixed-dose combination complete regimen approved for HIV infection. It is indicated for adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) and on a stable ART regimen for ≥6 months with no history of treatment failure and no known substitutions associated with resistance to dolutegravir or rilpivirine.

Elvitegravir/cobicistat/emtricitabine/tenofovir AF (Genvoya)

Antiretroviral combination product that provides a complete, once-daily regimen for treatment-naïve adults and adolescents aged ≥12 y, or to replace the current ART regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ART regimen for at least 6 months with no history of treatment failure. Each tablet contains an integrase inhibitor (elvitegravir 150 mg) and 2 NRTIs (emtricitabine 200 mg and tenofovir AF 10 mg). It also contains cobicistat, a CYP3A4 inhibitor used as a booster for elvitegravir, a CYP3A4 substrate.

Emtricitabine/rilpivirine/tenofovir AF (Odefsey)

Antiretroviral combination product that provides a complete, once-daily regimen for treatment-naïve adults and adolescents aged ≥12 y, or to replace the current ART regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ART regimen for at least 6 months with no history of treatment failure. Each tablet contains 1 NNRTI (rilpivirine 25 mg) and 2 NRTIs (emtricitabine 200 mg and tenofovir AF 25 mg).

Elvitegravir/cobicistat/emtricitabine/tenofovir DF (Stribild)

Antiretroviral combination product that provides a complete, once-daily regimen for treatment-naïve adults. Contains an integrase inhibitor and 2 NRTIs plus cobicistat, a CYP3A4 inhibitor used as a booster for elvitegravir, a CYP3A4 substrate. Cobicistat enhances the systemic exposure of CYP3A substrates, such as elvitegravir, where bioavailability is limited and half-life is shortened by CYP3A-dependent metabolism.

Emtricitabine/rilpivirine/tenofovir DF (Complera)

Complete regimen combination consisting of 2 NRTIs and 1 NNRTI. It is indicated for treatment of HIV-1 infection in patients aged ≥12 years with no antiretroviral treatment history and with HIV-1 RNA ≤100,000 copies/mL at the start of therapy, and in certain virologically-suppressed (HIV-1 RNA <50 copies/mL) patients on a stable antiretroviral regimen at start of therapy in order to replace their current antiretroviral treatment regimen.

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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)

This is a NRTI combination product. It is indicated in combination with other ART agents (eg, NNRTIs, PIs) for the treatment of HIV-1 infection in adults and pediatric patients aged 12 years or older. It is also indicated in combination with safer sex practices for preexposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults at high risk. This indication is based on clinical trials in men who have sex with men (MSM) at high risk for HIV-1 infection and in heterosexual serodiscordant couples. CDC guidelines include additional populations (eg, IV drug users, heterosexual individuals at high risk).

Abacavir/dolutegravir/lamivudine (Triumeq)

Contains 2 NRTIs (abacavir 600 mg and lamivudine 300 mg) and an integrase strand inhibitor (dolutegravir 50 mg). Dosage modification may be required when coadministered with strong CYP3A4 inducers by adding a single-entity evening dose of dolutegravir.

Emtricitabine/tenofovir DF/efavirenz (Atripla)

NRTI and NNRTI combination product.

Lamivudine/zidovudine (Combivir)

NRTI combination product.

Emtricitabine/tenofovir DF (Truvada)

NRTI combination product. Indicated in combination with other ART agents (eg, NNRTIs, PIs) for the treatment of HIV-1 infection in adults. It is also approved for pediatric patients who weigh at least 17 kg and can swallow the tablet whole. It is also indicated in combination with safer sex practices for preexposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults at high risk. This indication is based on clinical trials in men who have sex with men (MSM) at high risk for HIV-1 infection and in heterosexual serodiscordant couples. CDC guidelines include additional populations (eg, IV drug users, heterosexual individuals at high risk).

Emtricitabine/tenofovir AF (Descovy)

NRTI combination product. Indicated in combination with other ART agents (eg, NNRTIs, PIs) for the treatment of HIV-1 infection in adults and pediatric patients aged 12 y or older. Unlike Truvada, it is not indicated for PrEP.

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CYP340 Inhibitors

Class Summary

Boosting agents (eg, ritonavir, cobicistat) may be part of various ART drug regimens to inhibit metabolism of ART CYP3A substrates, resulting in increased systemic exposure and efficacy.

Cobicistat (Tybost)

CYP3A inhibitor. As a single agent, it is indicated to increase systemic exposure of atazanavir or darunavir (once-daily dosing regimen) in combination with other antiretroviral agents. It was originally approved as part of the combination product elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild).

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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.

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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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