HIV Medications: All 9 Drug Classes, Recommended Regimens & Cost (2026)

HIV is treated with antiretroviral therapy (ART) using FDA-approved medications from nine drug classes recognized by the U.S. Department of Health and Human Services (DHHS): NRTIs, NNRTIs, INSTIs, protease inhibitors, fusion inhibitors, CCR5 antagonists, CD4 post-attachment inhibitors, gp120 attachment inhibitors, and capsid inhibitors. The most commonly recommended first-line regimens in 2026 are Biktarvy, Triumeq, and Dovato — all single-tablet, once-daily options. Long-acting injectables like Cabenuva and Yeztugo now offer alternatives to daily pills for treatment and prevention.

HIV medications (also called antiretroviral drugs or ARVs) are prescription medicines used to treat and prevent human immunodeficiency virus (HIV) infection. There are more than 30 FDA-approved antiretroviral medications used to treat HIV in the United States as of 2026 — and several more used to prevent it. These medications are grouped into nine drug classes based on how they block the virus at different stages of its life cycle. Source: DHHS “What to Start” Guidelines.

This guide explains every drug class, lists the current guideline-recommended regimens, covers emerging options like long-acting injectables and pipeline medications, and breaks down cost and access information. It is designed for patients, caregivers, and anyone trying to understand how HIV treatment works today.

No single HIV medication should ever be used alone. Treatment regimens combine drugs from different classes to suppress the virus effectively, prevent drug resistance, and allow the immune system to recover. Your clinician will choose the best combination based on your health profile, resistance testing, other medications, and preferences.

The Nine Classes of HIV Medications

HIV drugs are classified by the step in the viral life cycle they block. The DHHS guidelines recognize nine mechanistic classes of antiretroviral drugs. Understanding these classes helps you understand why your regimen combines specific medications and why switching one drug doesn’t always mean switching the whole regimen.

1. NRTIs — Nucleoside Reverse Transcriptase Inhibitors

NRTIs are drugs that provide defective building blocks that HIV needs to copy its genetic material. They were the first class of HIV drugs developed. When the virus incorporates these faulty building blocks, it cannot finish making copies of itself. NRTIs form the “backbone” of nearly all HIV treatment regimens.

Common NRTIs: tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), lamivudine (3TC), abacavir (ABC). Most are used as part of combination pills. Source: NIH HIVinfo.

2. NNRTIs — Non-Nucleoside Reverse Transcriptase Inhibitors

NNRTIs are drugs that target the same enzyme as NRTIs (reverse transcriptase) but work differently — they bind directly to the enzyme and change its shape so it can no longer function. NNRTIs are used in some first-line regimens and are a component of the injectable treatment Cabenuva.

Common NNRTIs: doravirine (DOR), rilpivirine (RPV), efavirenz (EFV). Compared to older NNRTIs like efavirenz, doravirine generally has fewer neuropsychiatric side effects and a more favorable drug interaction profile.

3. INSTIs — Integrase Strand Transfer Inhibitors

INSTIs are drugs that block the integrase enzyme HIV uses to insert its genetic code into human DNA. They are the cornerstone of modern HIV treatment and recommended as part of all preferred initial regimens in the current DHHS guidelines. INSTIs are preferred as first-line treatment because they combine high efficacy (over 90% viral suppression at 48 weeks in clinical trials), a high genetic barrier to resistance, fewer drug interactions than older classes, and a generally favorable side-effect profile compared to NNRTIs and PIs.

Current INSTIs: dolutegravir (DTG), bictegravir (BIC), cabotegravir (CAB, available as oral and injectable), raltegravir (RAL), elvitegravir (EVG). Dolutegravir and bictegravir are the most commonly prescribed. Compared to Biktarvy (bictegravir-based), Triumeq (dolutegravir-based) requires a negative HLA-B*5701 test, while Dovato (also dolutegravir-based) uses only two drugs instead of three. Source: DHHS Guidelines.

4. Protease Inhibitors (PIs)

PIs are drugs that block the protease enzyme, which HIV needs to cut long protein chains into the smaller pieces required to assemble new virus particles. Without functional protease, the virus produces immature, non-infectious copies. PIs are typically used with a pharmacokinetic enhancer (ritonavir or cobicistat) to boost their levels in the body.

Current PIs: darunavir (DRV, the only PI in current first-line guidelines), atazanavir (ATV). WHO’s 2026 updated guidelines confirm darunavir/ritonavir as the preferred PI when a PI-based regimen is needed. Source: WHO, Jan 2026.

5. Fusion Inhibitors

Fusion inhibitors are drugs that work outside the cell by blocking HIV from physically fusing with and entering CD4 cells. They are used for treatment-experienced patients with multi-drug-resistant HIV. Enfuvirtide (Fuzeon) is the only approved drug in this class. It requires twice-daily subcutaneous injection. Source: NIH HIVinfo.

6. CCR5 Antagonists

CCR5 antagonists are drugs that block the CCR5 coreceptor on the surface of CD4 cells, which some strains of HIV need to enter the cell. Maraviroc (Selzentry) is the only approved CCR5 antagonist. Before prescribing maraviroc, clinicians must perform a tropism test to confirm the patient’s HIV uses the CCR5 coreceptor (not the CXCR4 coreceptor or both). This class is used in specific clinical situations, not routine first-line treatment.

7. CD4 Post-Attachment Inhibitors

CD4 post-attachment inhibitors are drugs that block HIV after it has attached to the CD4 receptor but before it can enter the cell. Ibalizumab-uiyk (Trogarzo) is the only approved drug in this class. It is a monoclonal antibody administered by intravenous infusion every two weeks and is indicated for heavily treatment-experienced adults with multi-drug-resistant HIV who are failing their current antiretroviral regimen. Trogarzo was approved by the FDA in 2018 and represents a distinct mechanism from both fusion inhibitors and CCR5 antagonists. Source: NIH HIVinfo.

8. gp120 Attachment Inhibitors

gp120 attachment inhibitors are drugs that bind to the gp120 protein on the outer surface of HIV, preventing the virus from initially attaching to CD4 cells. Fostemsavir (Rukobia) is the only approved drug in this class. It is an oral medication taken twice daily and is indicated for heavily treatment-experienced adults with multi-drug-resistant HIV who cannot achieve viral suppression with other available regimens. Rukobia was approved by the FDA in 2020. Source: NIH HIVinfo.

9. Capsid Inhibitors

Capsid inhibitors are the newest class of HIV drugs. They target the protein shell (capsid) that protects HIV’s genetic material. The first and only approved capsid inhibitor is lenacapavir (Sunlenca for treatment, Yeztugo for PrEP), developed by Gilead Sciences. Lenacapavir is unique because it interferes with multiple stages of the viral life cycle and has an extremely long half-life, enabling dosing as infrequently as every six months.

Sunlenca was first approved in 2022 for heavily treatment-experienced adults with multi-drug-resistant HIV. Yeztugo was FDA-approved in June 2025 as a twice-yearly injectable PrEP option, representing a major breakthrough in HIV prevention.

Recommended First-Line Regimens (DHHS 2025–2026)

The U.S. Department of Health and Human Services (DHHS) maintains the authoritative Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, updated regularly based on new evidence. The current DHHS guidelines (updated 2025) recommend the following INSTI-based regimens for most people starting HIV treatment for the first time:

Recommended Initial Regimens for Most People

• Biktarvy (bictegravir + emtricitabine + tenofovir alafenamide) — one tablet, once daily, with or without food. The most prescribed HIV treatment in the U.S. as of 2026; known for a high barrier to resistance and favorable tolerability profile.
• Triumeq (dolutegravir + abacavir + lamivudine) — one tablet, once daily; requires negative HLA-B*5701 test before starting (to rule out abacavir hypersensitivity). Not recommended for patients with hepatitis B coinfection.
• Dovato (dolutegravir + lamivudine) — one tablet, once daily; a two-drug regimen suitable for patients with HIV RNA below 500,000 copies/mL and no hepatitis B coinfection. Uses fewer drugs than traditional three-drug regimens, potentially reducing long-term drug exposure.

All three are single-tablet regimens (STRs), meaning the entire treatment regimen is contained in one pill taken once a day. This simplicity improves adherence and is one reason these regimens are preferred.

Other Recommended Regimens for Certain Situations

• Cabenuva (cabotegravir + rilpivirine, injectable) — for virologically suppressed patients who prefer injections every one or two months instead of daily pills
• Delstrigo (doravirine + lamivudine + tenofovir disoproxil fumarate) — an NNRTI-based STR option when INSTIs cannot be used
• Symtuza (darunavir + cobicistat + emtricitabine + tenofovir alafenamide) — a PI-based STR for situations where INSTIs and NNRTIs are not appropriate

Single-Tablet Regimens: Comparison Table

Single-tablet regimens (STRs) combine two or three HIV drugs from one or more classes into a single pill. They are preferred by most guidelines because of improved adherence. The following table compares the major STRs available in the U.S. as of 2026. Compared to multi-tablet regimens, STRs reduce pill burden and have been associated with better adherence rates in clinical studies.

Abbreviations: BIC = bictegravir, DTG = dolutegravir, EVG = elvitegravir, DOR = doravirine, RPV = rilpivirine, DRV = darunavir, COBI = cobicistat, FTC = emtricitabine, 3TC = lamivudine, ABC = abacavir, TAF = tenofovir alafenamide, TDF = tenofovir disoproxil fumarate. Source: NIH HIVinfo, DHHS Guidelines.

Long-Acting Injectable HIV Medications

Long-acting injectables represent one of the most significant advances in HIV medicine, offering alternatives to daily pills for both treatment and prevention.

For Treatment

Cabenuva (cabotegravir + rilpivirine, injectable) is currently the only FDA-approved long-acting injectable for HIV treatment. It is administered as two intramuscular injections (one of each drug) by a healthcare provider every one or two months. Cabenuva is approved for adults who are already virologically suppressed on a stable oral regimen and have no history of treatment failure or resistance to cabotegravir or rilpivirine. Source: NIH HIVinfo.

Sunlenca (lenacapavir, injectable) is the first capsid inhibitor approved for treatment. It is given as a subcutaneous injection every six months, combined with other antiretrovirals. Sunlenca is specifically indicated for heavily treatment-experienced adults with multi-drug-resistant HIV — a population with very few other options. It is not used as a first-line treatment.

For Prevention (PrEP)

Yeztugo (lenacapavir, injectable) was approved by the FDA in June 2025 for HIV prevention (PrEP). It provides near-complete protection with just two injections per year, based on the landmark PURPOSE 1 and PURPOSE 2 clinical trials. Lenacapavir PrEP was named Science magazine’s 2024 Breakthrough of the Year. Source: Gilead/FDA.

Apretude (cabotegravir, injectable) is a bimonthly injectable PrEP option. It requires an injection every two months administered by a healthcare provider, following an initial oral lead-in period.

Pre-Exposure Prophylaxis (PrEP): Medications for HIV Prevention

Pre-exposure prophylaxis (PrEP) is medication taken by HIV-negative individuals to prevent HIV infection. When taken as prescribed, PrEP is highly effective. As of 2026, PrEP is recommended by the CDC for anyone at substantial risk of HIV acquisition. The following PrEP options are FDA-approved:

PrEP is available to anyone at risk of HIV. In the U.S., the Ready, Set, PrEP program provides PrEP at no cost to people without insurance or whose insurance does not cover it.

Side Effects of HIV Medications: What to Expect

Modern HIV medications are generally well tolerated, especially compared to earlier-generation drugs. However, all medications have potential side effects, and your clinician will monitor for specific concerns based on your regimen.

Common Short-Term Side Effects

When starting a new HIV regimen, some people experience initial side effects that typically resolve within the first two to six weeks. These may include nausea, diarrhea, headache, fatigue, dizziness, and difficulty sleeping. INSTI-based regimens (Biktarvy, Triumeq, Dovato) generally have the fewest side effects among current first-line options, which is one reason they are preferred by guidelines. If side effects persist beyond several weeks or are severe enough to interfere with daily activities, talk to your clinician — a regimen change may be possible.

Weight Gain and Metabolic Changes

Weight gain has emerged as one of the most discussed concerns in HIV treatment. Clinical data suggest that newer INSTI-based regimens — particularly those combining dolutegravir or bictegravir with tenofovir alafenamide (TAF) — are associated with greater weight gain than older regimens. This effect may disproportionately affect women and Black patients.

The DHHS guidelines include a dedicated section on this topic, noting that while the mechanism is not fully understood, contributing factors may include a return to health after HIV suppression, effects of specific drugs on metabolic pathways, and the switch away from older agents like tenofovir disoproxil fumarate (TDF) that were associated with less weight gain. Your clinician should discuss this concern with you and monitor weight and metabolic markers (blood sugar, cholesterol) at regular intervals. Source: DHHS Guidelines.

Long-Term Monitoring

HIV medications require ongoing monitoring to ensure safety over years and decades of use. Your clinician will regularly check kidney function (especially with TDF-containing regimens), bone mineral density (particularly in postmenopausal women and older adults), liver function, lipid profiles, and blood glucose levels. Some older NNRTIs like efavirenz were associated with neuropsychiatric effects; newer options like doravirine generally have a better profile. Your monitoring schedule will depend on your specific regimen and health status.

Drug Resistance: What It Is and How to Prevent It

Drug resistance occurs when HIV mutates in ways that allow it to replicate even in the presence of antiretroviral medications. Resistance is one of the most important considerations in HIV treatment because it can limit future treatment options.

How Resistance Develops

Resistance typically develops when drug levels in the body are too low to fully suppress the virus but high enough to exert selective pressure — creating an environment where resistant mutations have an advantage. The most common cause is inconsistent adherence (missing doses), but resistance can also develop from suboptimal drug regimens, drug interactions that lower medication levels, or transmission of already-resistant virus from another person (transmitted resistance).

Resistance Barrier and Regimen Choice

Different drugs have different “barriers to resistance.” Drugs with a high barrier to resistance require multiple mutations to become ineffective, making resistance harder to develop. This is one reason current guidelines prefer INSTIs like dolutegravir and bictegravir — they have a high barrier to resistance. Older INSTIs like raltegravir and elvitegravir have a lower resistance barrier. Protease inhibitors (boosted with ritonavir or cobicistat) also have a high barrier to resistance.

Resistance Testing

The DHHS guidelines recommend resistance testing for all patients before starting treatment and when treatment failure occurs. Genotypic resistance testing identifies specific mutations in HIV that predict reduced susceptibility to certain drugs. This helps clinicians select an effective regimen and avoid drugs that will not work against your specific virus. Source: DHHS Guidelines.

Adherence: The Best Prevention for Resistance

Taking your medication consistently — every dose, every day, on time — is the single most important thing you can do to prevent drug resistance. Strategies that may help include using a pill organizer, setting phone reminders, building medication into a daily routine, choosing a regimen that fits your lifestyle (e.g., no food requirements), and discussing long-acting injectable options like Cabenuva if daily pills are a barrier. If you are struggling with adherence, tell your clinician — there is no judgment, and there are solutions.

Drug Interactions

HIV medications can interact with other prescription drugs, over-the-counter medications, supplements, and even some foods. Drug interactions can reduce the effectiveness of your HIV treatment, increase side effects, or affect the levels of your other medications. Common categories of interactions include antacids and acid reducers (which can reduce absorption of rilpivirine and some INSTIs), certain antibiotics and antifungals, cholesterol-lowering statins, hormonal contraceptives, and herbal supplements like St. John’s wort (which can dramatically reduce levels of many HIV drugs).

Before starting any new medication, supplement, or herbal product, always tell your clinician and pharmacist that you take HIV medications. The DHHS maintains a comprehensive, searchable drug interaction database at ClinicalInfo.HIV.gov. The University of Liverpool also provides a widely used HIV drug interaction checker available for free online.

HIV Medications and Pregnancy

Antiretroviral therapy during pregnancy is essential to protect both the parent and the baby. With proper treatment, the risk of perinatal HIV transmission can be reduced to less than 1%. However, regimen choice may change during pregnancy. The DHHS maintains separate Perinatal Guidelines that address which medications are preferred, which should be avoided, and how dosing may need to be adjusted.

Dolutegravir-based regimens are currently recommended as preferred options during pregnancy based on extensive safety data. Earlier concerns about a possible association between dolutegravir and neural tube defects (from the Tsepamo study in Botswana) have been substantially mitigated by larger studies showing a very small absolute risk. Bictegravir has less pregnancy safety data, and some regimen adjustments may be needed. If you are pregnant, planning to become pregnant, or breastfeeding, discuss your HIV treatment with your clinician as soon as possible. Source: DHHS Perinatal Guidelines.

Pipeline: New HIV Medications in Development (2026–2027)

Several important new HIV medications and formulations are in late-stage clinical development. While none are yet approved, they represent the next generation of treatment and prevention.

Bictegravir/Lenacapavir (BIC/LEN) — Gilead Sciences

Gilead is developing a once-daily single-tablet regimen combining bictegravir (the INSTI in Biktarvy) with lenacapavir (the capsid inhibitor). Phase 3 ARTISTRY-1 and ARTISTRY-2 trial results presented at CROI 2026 showed BIC/LEN maintained virological suppression when patients switched from either complex multi-tablet regimens or from Biktarvy. A regulatory filing is expected, with a potential launch in 2027. This two-drug combination targets a key unmet need: simplification for patients on complex regimens, particularly those aging with HIV. Source: Gilead press release, CROI 2026 (ARTISTRY-1).

Islatravir — Merck

Islatravir is a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI) — a new mechanism within the NRTI class. It has an extremely long intracellular half-life, which could enable weekly oral dosing or long-acting implant formulations. In Phase 3 trials, participants who switched to a once-daily islatravir/doravirine combination pill maintained an undetectable viral load for 48 weeks, and the combination has also shown efficacy in treatment-naive patients. Merck is also studying islatravir for prevention. Earlier development was slowed by dose-related lymphocyte count declines, but lower doses resolved this issue. Source: SFAF Pipeline Review, Jan 2026.

VH-184 — ViiV Healthcare

VH-184 is a third-generation integrase inhibitor with activity against HIV strains resistant to dolutegravir and bictegravir. Phase 1 data presented at CROI 2026 demonstrated a long-acting formulation that could support twice-yearly dosing, and an enhanced resistance profile compared to existing INSTIs. A proof-of-concept efficacy study is ongoing. VH-184 addresses INSTI resistance, a growing concern as dolutegravir and bictegravir become the global standard of care. Source: ViiV Healthcare, CROI 2026.

VH-499 — ViiV Healthcare

VH-499 is an investigational capsid inhibitor separate from lenacapavir, also being developed by ViiV Healthcare as a long-acting injectable. Phase 1 data presented at CROI 2026 supported twice-yearly dosing potential. Having a second capsid inhibitor in development is significant because it could provide an alternative for patients who develop resistance to lenacapavir.

Broadly Neutralizing Antibodies (bNAbs)

Multiple research groups and companies are studying broadly neutralizing antibodies — immune proteins that can recognize and neutralize a wide range of HIV variants — as potential long-acting treatments or functional cures. These are administered by infusion or injection. While still largely in early to mid-stage trials, bNAbs represent a fundamentally different approach to HIV treatment and could eventually complement or partially replace traditional antiretrovirals. Source: NIAID/NIH.

Weekly and Monthly Oral Options

Multiple companies are developing less-frequent oral HIV pills. Gilead is testing a once-weekly combination of its integrase inhibitor GS-1720 plus a lenacapavir prodrug (GS-4182) in Phase 2 WONDERS trials, and a potential once-monthly oral capsid inhibitor (GS-3107) in Phase 1. Merck and Gilead are also collaborating on a once-weekly pill combining islatravir and lenacapavir. For prevention, Merck’s MK-8527 (a once-monthly oral NRTTI) is in Phase 3 trials (EXPrESSIVE-10 and EXPrESSIVE-11) for PrEP. No weekly or monthly oral HIV drug has been approved yet, but multiple trials are underway. Source: SFAF Pipeline Review, Jan 2026.

HIV Medication Cost Comparison and How to Get Help

HIV medication list prices in the U.S. are among the highest in the world. However, what patients actually pay varies enormously based on insurance coverage, assistance programs, and pharmacy. The table below shows approximate list prices for reference — most patients pay significantly less.

Prices are approximate WAC (wholesale acquisition cost) per 30-day supply as of early 2026. Copay card amounts apply to commercially insured patients only — not Medicare, Medicaid, or other government insurance. Sources: manufacturer price info pages, DHHS.

Cost Assistance Programs

Most people living with HIV do not pay the full listed price. The following programs can significantly reduce or eliminate out-of-pocket costs:

• Manufacturer copay cards and PAPs — Gilead, ViiV, Merck, and Janssen all offer copay assistance for commercially insured patients and free medication for qualifying uninsured patients (see links in table above)
• Ryan White HIV/AIDS Program / ADAP — federally funded safety net providing medications and medical care; find your state program at NASTAD or locate a clinic at findhivcare.hrsa.gov
• 340B Drug Pricing Program — certain safety-net providers receive discounted drug prices; ask your clinic if they participate. HRSA 340B Program
• Nonprofit copay foundations — Patient Advocate Foundation, PAN Foundation, HealthWell Foundation
• Ready, Set, PrEP — free PrEP for uninsured individuals at HIV.gov
• Medicare Extra Help (Low-Income Subsidy) — reduces Part D costs for qualifying beneficiaries at SSA.gov

For a detailed breakdown of one specific medication’s cost with and without insurance, see our Biktarvy Cost Guide.

Undetectable = Untransmittable (U=U)

One of the most important messages in HIV medicine today is U=U: Undetectable = Untransmittable. This means that people living with HIV who take antiretroviral therapy and achieve and maintain an undetectable viral load (fewer than 200 copies/mL) have effectively no risk of sexually transmitting HIV to their partners.

U=U is supported by rigorous scientific evidence from three landmark studies (HPTN 052, PARTNER/PARTNER2, and Opposites Attract) that collectively observed zero linked HIV transmissions from virally suppressed partners across tens of thousands of sexual encounters. U=U is endorsed by the NIH, the CDC, and over 1,100 organizations in 105 countries.

This concept underscores why early treatment initiation and consistent adherence matter not only for individual health but also for prevention at the community level. Source: NIAID Treatment as Prevention.

Explore Specific Medications

Frequently Asked Questions

Authoritative Resources

The following government and medical organization resources provide the most current and reliable information on HIV treatment and prevention:

• HIVinfo.NIH.gov — NIH’s patient-facing HIV information, drug database, and fact sheets
• ClinicalInfo.HIV.gov — HHS treatment guidelines, drug interaction database, and clinical resources
• DHHS Drug Interaction Database — Searchable tool for checking HIV drug interactions
• Liverpool HIV Drug Interaction Checker — University of Liverpool’s comprehensive interaction tool
• CDC HIV Nexus — CDC guidelines for screening, prevention, and care
• HIV.gov — Federal HIV resources, testing locator, and PrEP program information
• WHO HIV Guidelines — Global clinical recommendations
• NIAID HIV/AIDS — Research updates from the National Institute of Allergy and Infectious Diseases
• UNAIDS AIDSinfo — Global HIV statistics and country data
• Find HIV Care (HRSA) — Locate Ryan White clinics and testing sites
• National HIV Curriculum — Free CME-accredited education for healthcare providers