A Research Guide for
Living with HIV/AIDS

FDA-APPROVED Cabenuva is the first complete long-acting injectable ART regimen. Instead of taking daily pills, patients receive two intramuscular injections every two months (after an initial monthly phase). The ATLAS-2M trial demonstrated that bimonthly injections were non-inferior to monthly injections. This offers a major quality-of-life improvement for people who prefer not to take daily medication, have adherence challenges, or want to reduce the daily reminder of their diagnosis.

FDA-APPROVED Lenacapavir is a first-in-class capsid inhibitor that works by a completely novel mechanism — interfering with the HIV capsid at multiple stages of the viral life cycle. Initially approved for treatment-experienced patients with multidrug-resistant HIV (CAPELLA trial, NCT04150068), it requires subcutaneous injection only every 26 weeks (twice yearly). It is now being studied as part of first-line treatment regimens and for PrEP.

FDA-APPROVED Ibalizumab is a first-in-class CD4-directed post-attachment inhibitor — a monoclonal antibody given by intravenous infusion every two weeks. The FDA approved it in 2018 for adults with multidrug-resistant HIV-1 who are heavily treatment-experienced and failing their current regimen, based on the TMB-301 trial (NCT02475629). It is used together with other active antiretrovirals as part of a deep-salvage regimen — for example alongside agents such as fostemsavir and lenacapavir — for the small number of people whose virus has become resistant to most standard drug classes.

FDA-APPROVED Injectable cabotegravir for PrEP (Apretude) is given every two months and was shown to be superior to daily oral tenofovir/emtricitabine (Truvada/Descovy) in the HPTN 083 (MSM/transgender women) and HPTN 084 (cisgender women) trials. This is a game-changer for prevention, removing the need for daily pill adherence.

FDA-APPROVED On June 18, 2025, the FDA approved lenacapavir for PrEP under the brand name Yeztugo — the first and only twice-yearly injectable option for HIV prevention. It is indicated to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who are at risk. The PURPOSE 1 trial in cisgender women in South Africa and Uganda showed zero HIV infections among 2,134 participants receiving twice-yearly lenacapavir injections; PURPOSE 2 (in MSM, transgender people, and cisgender women across multiple countries) recorded only two infections among 2,179 participants (99.9% remained HIV-negative). Initiation involves oral tablets on the first two days plus the first injection, then a subcutaneous injection every 6 months. Note: the PrEP brand (Yeztugo) is distinct from Sunlenca, the lenacapavir brand used to treat multidrug-resistant HIV.

FDA-APPROVED Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) with a high barrier to resistance, excellent tolerability, and proven efficacy. It is the backbone of WHO-recommended first-line ART globally. Dolutegravir/lamivudine (Dovato) demonstrated that effective ART can be achieved with just two drugs instead of three, reducing long-term medication burden (GEMINI-1/2 trials).

FDA-APPROVED In April 2026 the FDA approved IDVYNSO (doravirine + islatravir), a once-daily complete regimen of just two drugs that does not contain a tenofovir backbone — an option for some adults whose HIV is already well-controlled and who want to switch from a regimen that is working (it is approved as a switch option, not for people just starting treatment). Islatravir is a new long-acting agent; an investigational once-weekly oral islatravir + lenacapavir combination is also in Phase 3 testing (ISLEND-1 and ISLEND-2) but is not yet approved.

INVESTIGATIONAL Broadly neutralizing antibodies are antibodies that can neutralize many different strains of HIV. They are being studied for both treatment and prevention. Some combinations (e.g., VRC01, 3BNC117 + 10-1074) have shown the ability to maintain viral suppression for weeks to months without ART in some patients. If successful, they could offer long-acting treatment options and potentially contribute to functional cure strategies.

• 4th-generation antigen/antibody test (laboratory): Detects both HIV antibodies and p24 antigen. Can detect HIV as early as 18–45 days after exposure. This is the recommended initial screening test.
• Rapid antigen/antibody test (point-of-care): Finger-prick blood test with results in 20–30 minutes. Window period approximately 18–90 days.
• HIV RNA test (viral load / NAT): Detects the virus itself. Can detect HIV as early as 10–33 days after exposure. Used to confirm acute HIV infection and monitor treatment.
• Self-test kits (OraQuick): Oral fluid test available without a prescription. Results in 20 minutes. Window period approximately 23–90 days. A reactive result must be confirmed with a laboratory test.

Important: No test can detect HIV immediately after exposure. The “window period” is the time between potential exposure and when a test can reliably detect infection. If tested too early, a negative result does not rule out recent infection.

The CDC-recommended testing algorithm uses a stepwise approach:

1. Step 1: 4th-generation antigen/antibody immunoassay (screening)
2. Step 2: If reactive, perform HIV-1/HIV-2 antibody differentiation immunoassay
3. Step 3: If Step 2 is indeterminate or negative, perform HIV-1 RNA (NAT) test to detect acute infection

A confirmed positive result means HIV is present and treatment should begin promptly.

After a confirmed HIV diagnosis, the following tests are typically ordered before starting treatment:

• HIV viral load (RNA): Measures the amount of virus in the blood
• CD4 count: Measures immune function
• HIV genotype (resistance testing): Identifies mutations that may affect drug choice
• HLA-B*5701: Tested before using abacavir (to avoid hypersensitivity reaction)
• Tropism testing: If considering maraviroc (CCR5 inhibitor)
• Hepatitis B and C serologies: Coinfection affects treatment choice
• Complete metabolic panel, CBC, lipids, urinalysis: Baseline organ function
• Tuberculosis screening: TB/HIV coinfection is common globally
• STI screening: Syphilis, gonorrhea, chlamydia
• Pregnancy test (if applicable)

• What is my viral load and CD4 count?
• Has resistance testing been done? Are there any drug-resistance mutations?
• Do I have hepatitis B or C coinfection?
• How soon can I start treatment?
• Am I a candidate for same-day ART initiation?
• Should my sexual partners be notified and tested?
• What support services are available (case management, mental health, housing)?
• How do I protect my partners while waiting to become undetectable?

Rapid ART initiation (starting on the day of diagnosis or within 7 days) has become the standard of care. Research shows that rapid start:

• Improves linkage to care and retention
• Achieves viral suppression faster
• Reduces the time a person can transmit HIV
• Is safe and well-tolerated in most patients

The approach: After a confirmed diagnosis, baseline labs are drawn, resistance testing is sent, and ART is started with a recommended first-line regimen (typically bictegravir/emtricitabine/TAF or dolutegravir/lamivudine). If resistance results later show the need for a change, the regimen is adjusted. This is far better than delaying treatment weeks for lab results.

Exceptions: Rapid start requires caution in patients with suspected cryptococcal meningitis (CD4 <100, symptoms) or active tuberculosis, where starting ART too quickly can trigger immune reconstitution inflammatory syndrome (IRIS).

• Achieve undetectable viral load (<50 copies/mL) within 12–24 weeks of starting treatment
• Restore and preserve CD4 count
• Prevent HIV-related illness and death
• Prevent transmission (U=U)
• Minimize drug toxicity and interactions

Why integrase inhibitors? Modern INSTIs (bictegravir, dolutegravir) have an exceptionally high barrier to resistance, excellent tolerability, rapid viral suppression, and few drug interactions compared to older drug classes (PIs, NNRTIs).

• Doravirine / lamivudine / TDF (Delstrigo): NNRTI-based single-tablet option. Lower weight gain than INSTIs. Useful if weight is a concern.
• Darunavir/cobicistat + emtricitabine/TAF (Symtuza): Boosted PI-based regimen. High barrier to resistance. Requires food. More drug interactions.
• Raltegravir + emtricitabine/TDF: Safe in pregnancy (most data). Twice-daily raltegravir dosing.
• Cabotegravir + rilpivirine (Cabenuva): Long-acting injectable for virally suppressed patients (see next section).

• Which ART regimen is best for me, and why?
• Are there any drug interactions with my other medications?
• What side effects should I watch for?
• Am I a candidate for a two-drug regimen?
• Am I a candidate for long-acting injectable treatment?
• How often will my viral load and CD4 count be checked?
• What happens if I miss a dose?
• Is there a generic option available that could reduce my cost?
• Do I have hepatitis B, and how does that affect my treatment?
• Should I be screened for drug resistance before switching?

FDA-APPROVED Cabenuva is a two-injection regimen (cabotegravir into one gluteal muscle, rilpivirine into the other) given every two months after an initial oral lead-in or monthly injection period.

Key trials:

• ATLAS (NCT02951052): Monthly injections non-inferior to daily oral ART
• FLAIR (NCT02938520): Switch from daily dolutegravir-based ART to monthly injections maintained viral suppression
• ATLAS-2M (NCT03299049): Bimonthly injections non-inferior to monthly

Candidacy: Patients must be virally suppressed (<50 copies/mL) on oral ART, with no history of resistance to cabotegravir (INSTI) or rilpivirine (NNRTI). Not suitable for patients with prior NNRTI resistance mutations.

Practical considerations: Requires clinic visits every 2 months. Injection site reactions are common (pain, swelling) but generally mild and decrease over time. Must not miss injection windows — resistance can develop if drug levels decline.

FDA-APPROVED Lenacapavir is a first-in-class capsid inhibitor approved for adults with multidrug-resistant HIV (CAPELLA trial). It is given as a subcutaneous injection every 6 months (26 weeks), combined with an optimized background regimen.

Now also approved for prevention: Lenacapavir is FDA-approved as PrEP under the brand name Yeztugo (June 18, 2025), based on the PURPOSE 1/2 trials. It is also being studied in treatment-naive patients in combination with other agents, where it could become the backbone of ultra-long-acting HIV treatment.

Practical considerations: Subcutaneous injection (not intramuscular like Cabenuva). Injection site reactions including nodules can occur. For HIV treatment, the Sunlenca brand is currently indicated for multidrug-resistant HIV; the Yeztugo brand covers PrEP.

• Transmitted drug resistance (TDR): A person is infected with a strain of HIV that already carries resistance mutations. This is why resistance testing before starting ART is essential. TDR rates in the US are approximately 15–20% for at least one drug class.
• Acquired resistance: Develops during treatment, usually due to incomplete viral suppression from poor adherence or drug interactions. The virus develops mutations that allow it to escape the drugs being used.

• Take ART exactly as prescribed, every day
• Use regimens with a high barrier to resistance (bictegravir, dolutegravir)
• Ensure resistance testing is done before starting or changing ART
• Address adherence barriers (cost, side effects, mental health, substance use)
• Do not share medications or use partial regimens

• Is my viral load undetectable?
• What is my CD4 count, and is it improving?
• How are my kidneys and liver functioning on this medication?
• Am I due for any vaccinations?
• Should I be screened for cervical or anal cancer?
• How is my cardiovascular risk?
• Am I gaining weight, and is it related to my ART?

• Hepatitis B (HBV): Affects ~5–10% of people with HIV in the US. Several ART drugs (TAF, TDF, emtricitabine, lamivudine) are active against HBV. Stopping these drugs can cause dangerous HBV flares. All people with HIV should be vaccinated against HBV if not immune.
• Hepatitis C (HCV): Affects ~25% of people with HIV in the US. Direct-acting antivirals (DAAs) cure >95% of HCV, even in HIV coinfection. HCV treatment is highly recommended for all coinfected patients.

• Cardiovascular disease: People with HIV have an estimated 1.5–2x increased risk of cardiovascular events, driven by chronic inflammation, some ART drugs, and traditional risk factors. ASCVD risk should be managed aggressively.
• Weight gain: INSTIs (particularly dolutegravir and bictegravir) and TAF are associated with weight gain, especially in Black women. This is an active area of research and may influence regimen choice.
• Bone density: TDF (tenofovir disoproxil fumarate) causes more bone mineral density loss than TAF. Screening with DEXA scan may be appropriate for people with risk factors.
• Kidney disease: TDF can cause renal tubulopathy. TAF is kidney-sparing. Monitor renal function, especially with TDF-based regimens.

People with HIV have increased rates of certain cancers:

• Cervical cancer: Annual Pap smears recommended for women with HIV (more frequent than general population)
• Anal cancer: Anal Pap smears recommended for MSM and others at high risk. The ANCHOR trial showed that treating high-grade anal squamous intraepithelial lesions reduces anal cancer risk by 57%.
• Kaposi sarcoma and lymphoma: Risk decreases dramatically with viral suppression but remains elevated
• Lung cancer: Low-dose CT screening for people with significant smoking history

PEP must be started within 72 hours of potential exposure (the sooner the better). It involves taking ART for 28 days to prevent HIV infection after a high-risk exposure (condomless sex with a person of unknown status, needlestick injury, sexual assault).

Recommended PEP regimen: bictegravir/emtricitabine/TAF (Biktarvy) or dolutegravir + emtricitabine/TDF for 28 days. Contact an emergency department or urgent care clinic immediately after potential exposure.

Undetectable = Untransmittable (U=U) is one of the most important public health messages in HIV history. Three landmark studies established this:

• HPTN 052: 96% reduction in transmission from virally suppressed partners
• PARTNER / PARTNER2: Zero transmissions from virally suppressed partners among nearly 130,000 acts of condomless sex
• Opposites Attract: Zero transmissions among MSM serodiscordant couples when the HIV-positive partner was virally suppressed

U=U is endorsed by the CDC, NIH, UNAIDS, IAS, and over 1,100 organizations in 105 countries. It is settled science.

• Am I a candidate for PrEP? Which type would be best for me?
• If I am on ART, is my viral load undetectable, confirming U=U protection?
• Should my partners be on PrEP?
• How do I access PEP if I have a high-risk exposure?
• Are injectable PrEP options available at this clinic?
• What STI screening should I receive alongside PrEP?

As of 2026, a small number of people have been functionally cured of HIV through stem cell transplants from donors with a CCR5-delta32 mutation (a genetic variant that prevents HIV entry into cells):

• Timothy Ray Brown (“Berlin Patient”): First person cured (2008). Received a CCR5-delta32 bone marrow transplant for leukemia. Remained HIV-free until his death from cancer in 2020.
• Adam Castillejo (“London Patient”): Cured following a similar transplant for Hodgkin lymphoma (2019 confirmation).
• “Düsseldorf Patient,” “New York Patient,” “City of Hope Patient”: Additional cases of HIV remission following CCR5-delta32 transplants.

Important: Stem cell transplant is too risky and impractical for the vast majority of people with HIV. These cases prove a cure is possible but are not a scalable strategy. They have, however, fueled research into gene therapy approaches that might achieve the same result without a transplant.

• Gene therapy (CCR5 editing): Using CRISPR or other gene-editing tools to modify a person’s own immune cells to be resistant to HIV by disrupting the CCR5 co-receptor. Several trials are in early phases.
• Shock and kill: Using drugs (latency-reversing agents) to “wake up” latent HIV from its hiding places, making it visible to the immune system or ART for elimination. Results have been mixed so far.
• Broadly neutralizing antibodies (bNAbs): Engineered antibodies that target conserved regions of HIV. Being studied for sustained viral suppression without ART and as part of combination cure approaches.
• Therapeutic vaccines: Vaccines designed to boost the immune system’s ability to control HIV without ART. Multiple candidates in clinical trials, none yet successful.
• Block and lock: Keeping latent HIV permanently silenced so it can never reactivate, even without ART. Early-stage research.

• WHO recommendations (2024): Dolutegravir-based ART is the preferred first-line globally. WHO recommends ART for all people living with HIV regardless of CD4 count. Same-day ART initiation is recommended.
• PEPFAR: The US President’s Emergency Plan for AIDS Relief has provided ART to over 20 million people in sub-Saharan Africa and other high-burden regions. PEPFAR is the largest global health program for a single disease.
• The Global Fund: Finances ART access in over 100 countries
• UNAIDS 95-95-95 targets: By 2025, 95% of people with HIV know their status, 95% of those diagnosed are on ART, and 95% of those on ART are virally suppressed

• DHHS (US): Comprehensive ART guidelines, updated frequently
• IAS-USA: International AIDS Society — USA Panel recommendations
• WHO: Global consolidated HIV guidelines; drives LMIC treatment policy
• EACS (Europe): European AIDS Clinical Society guidelines
• BHIVA (UK): British HIV Association guidelines
• NICE (UK): Technology appraisals for ART access through NHS

DE-ADOPTED AZT (zidovudine) was the first approved antiretroviral drug (1987). Used alone, it provided only temporary benefit as resistance developed rapidly. It also caused significant side effects (anemia, nausea, myopathy). AZT monotherapy was replaced by combination therapy (“triple cocktail”) in 1996, which transformed HIV from a death sentence to a manageable condition. AZT remains in some combination tablets but is no longer used alone.

SUPERSEDED Efavirenz-based regimens (including Atripla: efavirenz/emtricitabine/TDF) were the standard of care for over a decade. However, efavirenz has significant CNS side effects (vivid dreams, dizziness, depression), a low barrier to resistance (single K103N mutation causes failure), and has been superseded by integrase inhibitor-based regimens. WHO transitioned to dolutegravir-based first-line ART globally. Efavirenz is no longer a recommended first-line option in any major guideline.

FAILED Studies of boosted protease inhibitor monotherapy (e.g., lopinavir/ritonavir or darunavir/ritonavir alone) as maintenance showed higher rates of low-level viremia and viral blips in sanctuary sites (CNS, genital tract) compared to triple-drug ART. This approach is not recommended.

FAILED Despite decades of effort, no preventive HIV vaccine has succeeded in clinical trials:

• STEP / Phambili (Merck Ad5): Halted in 2007; vaccine may have increased HIV risk
• RV144 (Thai Trial): Only trial showing partial efficacy (~31%), but too low for licensure
• HVTN 702 (Uhambo): Follow-up to RV144 in South Africa; stopped for futility in 2020
• Imbokodo (J&J mosaic vaccine): Stopped for futility in 2021; only 25% efficacy
• Mosaico (J&J): Stopped for futility in 2023; no significant efficacy in MSM

mRNA vaccine platforms are now being explored, leveraging COVID-19 vaccine technology. The extreme genetic diversity of HIV remains the fundamental challenge.

DE-ADOPTED These early NRTIs caused severe mitochondrial toxicity including lipodystrophy (fat redistribution), peripheral neuropathy, lactic acidosis, and pancreatitis. WHO recommended against d4T in 2010. Both drugs have been replaced by safer alternatives (TDF, TAF, abacavir) and should not be used.

• HIV stigma remains a significant barrier to testing, treatment, and quality of life. Internalized stigma can lead to depression, isolation, and poor adherence.
• Depression and anxiety are more common in people with HIV. Screening and treatment should be part of routine care.
• Disclosure is personal. There is no obligation to disclose HIV status to everyone. However, disclosure to sexual partners is legally required in many jurisdictions (though U=U changes the ethical landscape).
• Peer support through organizations like The Well Project, POZ.com, and local ASOs (AIDS Service Organizations) can reduce isolation.

More than half of people living with HIV in the US are over 50. Aging with HIV involves managing both HIV and age-related conditions:

• Regular cardiovascular, bone density, and metabolic screening
• Age-appropriate cancer screening (may be recommended earlier than general population)
• Polypharmacy management (drug interactions between ART and medications for comorbidities)
• Cognitive health monitoring
• Vaccination (including COVID-19, flu, pneumococcal, shingles, hepatitis A/B)

• People with HIV can have healthy pregnancies and HIV-negative babies. With effective ART and appropriate obstetric care, mother-to-child transmission rates are <1%.
• ART should be maintained throughout pregnancy. Biktarvy and dolutegravir-based regimens are preferred.
• Conception can occur naturally when the HIV-positive partner is virally suppressed (U=U). Preconception counseling is recommended.
• Breastfeeding while on suppressive ART is now supported in the US (DHHS 2023 update), though formula feeding eliminates all risk.

• HIV.gov: hiv.gov — US government HIV information and resources
• POZ.com: poz.com — News, community, personal stories
• The Well Project: thewellproject.org — HIV information for women
• NASTAD: nastad.org — State-level HIV/hepatitis programs and ADAP
• Ryan White HIV/AIDS Program: ryanwhite.hrsa.gov — Federal program providing HIV care
• National HIV/AIDS Hotline: 1-800-232-4636

• Am I up to date on all recommended vaccinations?
• Should I be screened for hepatitis C, STIs, or HPV-related cancers?
• Am I at increased cardiovascular risk, and what should I do about it?
• Is my ART causing weight gain, and should we consider alternatives?
• Am I a candidate for switching to long-acting injectable therapy?
• Should I see any other specialists (cardiologist, endocrinologist, psychiatrist)?
• What resources are available for financial assistance with my medications?
• Can I participate in a clinical trial?

• The reservoir problem: Within days of HIV infection, the virus integrates into the DNA of long-lived memory CD4+ T cells and enters a state of latency. These resting latently infected cells carry HIV DNA but produce no viral proteins, making them invisible to the immune system and unaffected by ART. ART can suppress active replication but cannot eliminate these cells. Even after 20+ years of successful ART, the reservoir persists. This is why HIV rebounds within weeks of stopping ART in most people.
• "Shock and kill" (latency reversal): Experimental agents (including histone deacetylase inhibitors like vorinostat, romidepsin, and panobinostat; toll-like receptor agonists; and PKC modulators) reactivate latent HIV, making infected cells visible to the immune system for clearance. Clinical trials have shown that these agents can increase HIV RNA in the blood of treated patients (proof of reactivation), but have not yet achieved measurable reservoir reduction or post-treatment viral control. This remains an active research area.
• "Block and lock" (deep latency): The opposite approach — locking the reservoir into permanently silenced HIV that cannot reactivate even without ART. Didehydro-cortistatin A (dCA) and other compounds are in early research.
• Gene therapy/gene editing: Approaches targeting the CCR5 gene (HIV’s main co-receptor for cell entry) aim to produce CCR5-deleted T cells that are naturally HIV-resistant, replicating the biology of the Berlin Patient and London Patient cures (achieved through bone marrow transplants from CCR5-Δ32/Δ32 donors). CRISPR-Cas9 gene editing to excise HIV DNA from infected cells is in very early development. Active clinical trials: NCT05765058 (gene editing), NCT04885933 (CCR5 gene therapy).
• Broadly neutralizing antibodies (bNAbs): bNAbs that target conserved regions of the HIV envelope protein can suppress viral replication and deplete the reservoir by marking infected cells for immune destruction. Clinical trials of bNAb combinations (VRC01, 3BNC117, 10-1074, N6LS) show that some combinations can maintain viral suppression for months after ART discontinuation in a subset of patients. bNAbs may bridge the gap between ART and cure, or function as long-acting preventive agents.
• HIV vaccines: Despite 40 years of effort, an effective HIV vaccine remains elusive due to HIV’s extreme genetic diversity, rapid mutation, and immune evasion. The only HIV vaccine to show efficacy in humans was RV144 (Thailand, 2009) — 31.2% efficacy over 3.5 years, too modest for deployment. mRNA vaccine platforms (used successfully for COVID-19) are now being applied to HIV: IAVI and Moderna’s germline-targeting mRNA approach (NCT05001373) showed the target immune response in 97% of trial participants, a promising step. Mosaic antigen vaccines (Ad26.Mos.HIV + gp140) are in Phase 2/3 trials. A truly effective HIV vaccine remains 5–15+ years from deployment.

• Universal screening recommendations: The CDC and USPSTF recommend that all Americans between 15 and 65 be tested for HIV at least once as part of routine medical care. Higher-risk individuals (MSM, people who inject drugs, individuals with multiple partners or recent STIs) should be tested every 3–12 months depending on risk level. Pregnant women should be tested at the first prenatal visit, and re-tested in the third trimester if at ongoing risk.
• HIV test types:
  • 4th-generation combination antigen/antibody (Ag/Ab) test: The current standard of care for laboratory HIV testing. Detects both HIV-1/2 antibodies AND HIV p24 antigen (which rises before antibodies), reducing the window period to 18–45 days after infection. Reactive results require confirmatory HIV-1/HIV-2 differentiation immunoassay plus RNA PCR if differentiation is inconclusive.
  • 3rd-generation antibody-only tests: Older tests with a longer window period (~23–90 days). Still used in some settings; do not detect acute infection as early.
  • Home tests: OraQuick In-Home HIV Test (oral fluid, result in 20 minutes; window period 23–90 days; sensitivity 92% — lower than lab tests, meaning some acute infections are missed). HIV Self-Test (finger-prick blood); sensitivity similar to OraQuick. Home tests are appropriate for ongoing monitoring; lab testing is recommended for recent possible exposures within 45 days.
  • Nucleic Acid Amplification Test (NAAT/RNA PCR): Detects HIV RNA directly; can diagnose HIV within 10–33 days of infection. Used to confirm reactive antigen/antibody tests and to diagnose acute HIV infection when serology is negative but clinical suspicion is high (fever, rash, lymphadenopathy within days-to-weeks of high-risk exposure).
• Where to get tested for free: CDC gettested.cdc.gov/testing directory; Planned Parenthood locations; federally qualified health centers (FQHCs); local health departments; HIV/AIDS service organizations (HASOs, find at HIV.gov); many pharmacies (CVS MinuteClinic).

• Rapid ART initiation: Same-day or next-day ART initiation ("Rapid ART") is now recommended by the DHHS HIV Treatment Guidelines for most newly diagnosed patients. Waiting weeks for labs before starting ART delays benefit and increases mortality. Rapid ART programs achieve viral suppression faster and improve retention in care. If offered same-day ART, ask what baseline labs will be ordered in parallel with starting treatment.
• Ryan White HIV/AIDS Program: For uninsured or underinsured Americans, the Ryan White program (funded by HRSA) provides comprehensive HIV care, medications, and support services at no or reduced cost through a network of clinics across all 50 states. The AIDS Drug Assistance Program (ADAP) within Ryan White covers ART medications for those who lack insurance coverage. Find services at hab.hrsa.gov or call 1-800-HIV-0440.
• What to expect at your first HIV clinic visit: Baseline labs (CD4 count, viral load, complete blood count, comprehensive metabolic panel, lipid panel, HbA1c, hepatitis A/B/C serology, syphilis/gonorrhea/chlamydia screening, STI panel, tuberculosis testing, genotype resistance testing, HLA-B*5701 test); vaccination review and update (hepatitis A/B, pneumococcal, COVID, flu, HPV); ART initiation or continuation; and mental health and social needs assessment.

• HIV-Associated Nephropathy (HIVAN): A specific form of focal segmental glomerulosclerosis caused by direct HIV infection of kidney podocytes. Classically presents as heavy proteinuria, rapidly declining GFR, and enlarged echogenic kidneys on ultrasound. Almost exclusively occurs in patients of African ancestry due to genetic variants in APOL1. ART dramatically reduces HIVAN incidence and can stabilize or partially reverse established HIVAN. Untreated HIVAN progresses to end-stage kidney disease (ESKD) in weeks to months.
• HIV-immune complex kidney disease: Including IgA nephropathy and lupus-like nephritis (HIVICK — HIV Immune Complex Kidney disease), associated with immune dysregulation in HIV. Less aggressive than HIVAN; responds to ART and sometimes immunosuppression.
• ART-related nephrotoxicity: Tenofovir disoproxil fumarate (TDF, older tenofovir form in Truvada, Atripla) causes dose-dependent proximal tubular injury — presenting as Fanconi syndrome (renal phosphate wasting, glycosuria, aminoaciduria) and can lead to declining GFR with prolonged use. Tenofovir alafenamide (TAF, in Biktarvy, Descovy, Odefsey) has markedly reduced renal toxicity and is preferred in patients with baseline kidney disease. If renal function is declining on TDF, switching to a TAF-containing regimen typically stabilizes or improves GFR.
• Cardiorenal syndrome and hypertension: The same cardiovascular risk factors that cause heart disease in HIV also damage kidneys: hypertension, diabetes, and dyslipidemia cause diabetic nephropathy and hypertensive nephrosclerosis. These are now the dominant causes of CKD in HIV in developed countries.

• Routine monitoring: Serum creatinine, eGFR, urinalysis with spot urine protein/creatinine ratio, and serum phosphate annually for all patients on TDF or at elevated CKD risk (hypertension, diabetes, older age, African American ancestry). More frequent monitoring (every 6 months) if eGFR <60 mL/min or proteinuria >300 mg/g.
• ART dose adjustments: Many ART drugs require dose adjustment for reduced kidney function. Atazanavir, darunavir, rilpivirine, and cobicistat-boosted regimens require monitoring. Bictegravir (in Biktarvy) should not be initiated if eGFR <30 mL/min. Dolutegravir (in Dovato, Triumeq) requires no renal dose adjustment. Consult HIV pharmacist or HIV specialist for ART optimization if eGFR declines below 60 mL/min.
• Nephrology co-management: Nephrologist co-management is recommended for any HIV patient with eGFR <60 mL/min, protein/creatinine ratio >300 mg/g, or unexplained rapid eGFR decline. HIVAN requires kidney biopsy for definitive diagnosis. Dialysis and kidney transplantation are available for HIV patients with ESKD; outcomes have dramatically improved in the ART era.

Injection drug use (IDU) accounts for approximately 6% of new HIV diagnoses in the United States (higher in rural areas and in Eastern Europe and Central Asia globally). People who inject drugs (PWID) with HIV face intersecting barriers to care: stigma, criminalization of drug use, housing instability, and co-occurring mental health conditions all reduce engagement in care and ART adherence.

• Syringe Service Programs (SSPs): SSPs provide sterile syringes, needles, cotton, cookers, and other injection equipment at no cost, dramatically reducing the risk of HIV and hepatitis C transmission through needle sharing. SSPs also provide naloxone (to reverse opioid overdose), wound care, HIV and hepatitis C testing, vaccination (hepatitis A/B), referral to addiction treatment, and connection to HIV care. Decades of research confirm SSPs reduce HIV transmission without increasing drug use. Find an SSP at nasen.org or contact your local health department.
• Opioid Use Disorder and HIV: Buprenorphine (Suboxone, Sublocade) and methadone are the most effective opioid use disorder treatments. Buprenorphine can be prescribed by certified physicians in office-based settings (no longer requires an X-waiver as of 2023). Methadone for OUD requires dispensing through a federally certified opioid treatment program (OTP). Both significantly improve HIV outcomes: patients with HIV on medication-assisted treatment (MAT) have higher ART adherence, lower viral loads, and lower HIV transmission rates. Drug-drug interactions between buprenorphine and ART are minimal; methadone has significant interactions with efavirenz and nevirapine (CYP3A4 induction causes methadone withdrawal — dose adjustment needed).
• Wound botulism and skin/soft tissue infections: PWID are at high risk for skin and soft tissue infections (SSTI), including abscesses, cellulitis, and necrotizing fasciitis. People with HIV who inject drugs should be counseled on proper wound care, the importance of seeking care early for any red/warm/swollen injection site, and the signs of septic thrombophlebitis. Wound botulism (from contaminated black tar heroin) requires immediate emergency evaluation.

• Alcohol: Heavy alcohol use (more than 4 drinks/day or 14/week) is associated with reduced ART adherence, accelerated liver fibrosis (compounded by hepatitis B or C coinfection), neurotoxicity, and increased sexual risk behavior. Brief intervention (FRAMES-based counseling at HIV clinic visits), naltrexone for alcohol use disorder (no significant ART interactions; improves outcomes in people with HIV), and referral to substance use treatment should be standard practice in HIV care for heavy drinkers.
• Methamphetamine (meth, crystal): Methamphetamine use is concentrated in MSM communities and is strongly associated with HIV sexual risk behavior, with ART non-adherence (even one or two days of missed doses during a meth binge can allow viral rebound), and with cognitive impairment that amplifies HIV neurocognitive effects. Contingency management — providing small financial incentives (vouchers, gift cards) for negative urine toxicology tests — is the most evidence-supported treatment for methamphetamine use disorder. Naltrexone shows some benefit for methamphetamine use disorder; no pharmacotherapy has strong evidence.
• Cannabis: Cannabis use is common among people with HIV and may provide some benefit for HIV-related nausea and appetite loss, peripheral neuropathy pain, and sleep disturbance. Cannabis does not appear to impair ART adherence or immune function at moderate use levels. However, smoked cannabis carries respiratory risks (pulmonary aspergillosis risk at very high frequency of use); oral cannabis formulations are safer. Cannabis use disorder (dependence) may be associated with depression and cognitive impairment. Medical cannabis is legal in many US states; discuss use openly with your HIV provider.

• Pneumocystis pneumonia (PCP/PJP) — CD4 <200: The most common AIDS-defining OI. Caused by Pneumocystis jirovecii fungus; presents as subacute progressive shortness of breath, dry cough, and low-grade fever. Prophylaxis: trimethoprim-sulfamethoxazole (TMP-SMX, Bactrim) one double-strength tablet daily — recommended for all patients with CD4 <200, can be discontinued once CD4 >200 for 3+ months on ART. Alternatives for sulfa allergy: dapsone + pyrimethamine + leucovorin, or atovaquone, or aerosolized pentamidine.
• Toxoplasma encephalitis — CD4 <100: Reactivation of latent Toxoplasma gondii (acquired from cat feces or undercooked meat) can cause brain abscess. Presents as focal neurological deficits, seizures, or altered mental status. Prophylaxis: TMP-SMX covers Toxoplasma in seropositive patients at the same dose as PCP prophylaxis. Avoid cleaning cat litter boxes without gloves if Toxoplasma IgG-positive.
• Cryptococcal meningitis — CD4 <100: Caused by Cryptococcus neoformans (fungus in bird droppings). Presents as subacute headache, fever, and stiff neck. Serum CrAg (cryptococcal antigen) screening is recommended for ART-naive patients with CD4 <100. Treated with amphotericin B + flucytosine induction, then fluconazole maintenance.
• Mycobacterium avium complex (MAC) — CD4 <50: Disseminated MAC causes fever, night sweats, weight loss, diarrhea, and anemia. Prophylaxis: azithromycin 1,200 mg weekly for CD4 <50; can be discontinued once CD4 >100 for 3+ months on ART.
• CMV retinitis — CD4 <50: Cytomegalovirus reactivation can destroy the retina, causing painless progressive visual loss and floaters. All patients with CD4 <50 should have a dilated ophthalmologic exam to screen for CMV retinitis. Treated with valganciclovir or IV ganciclovir.
• Critical alert: If you have CD4 <200 and develop new fever, cough, headache, neurological symptoms, or visual changes, seek medical evaluation promptly — do not wait to see if symptoms resolve on their own.

Cardiovascular disease (CVD): People with HIV have approximately 1.5–2x the cardiovascular risk of age-matched HIV-negative individuals. The mechanisms include:

• Chronic immune activation even with undetectable viral load drives systemic inflammation that damages arteries
• Some older ART drugs (especially thymidine analog NRTIs and older PIs) increase lipid levels and insulin resistance; modern INSTIs are generally lipid-neutral
• Traditional CVD risk factors (smoking, hypertension, diabetes, dyslipidemia) are more prevalent in the HIV population

CVD prevention in HIV: Use the D:A:D cardiovascular risk calculator (specifically validated for HIV) rather than standard Framingham/PCE calculators. Statins are indicated for most adults with HIV over 40 per current guidelines — note that many statins interact with ART. Simvastatin and lovastatin are CONTRAINDICATED with ritonavir- or cobicistat-boosted regimens due to markedly elevated statin levels; rosuvastatin, pravastatin, and pitavastatin are preferred. Smoking cessation is the highest-yield CVD risk reduction strategy in HIV.

Bone health: People with HIV have 3–4x the risk of osteoporosis compared to HIV-negative peers. Causes: HIV-related inflammation, older ART medications (tenofovir DF/TDF reduces bone mineral density, largely resolved by switching to tenofovir AF/TAF in modern regimens), vitamin D deficiency (common in HIV), and smoking.

• DEXA bone density scanning is recommended for all postmenopausal women and all men over 50 with HIV, and for any HIV patient with fragility fracture history
• Vitamin D 2,000 IU/day and calcium 1,200 mg/day (dietary preferred) are recommended for all adults with HIV
• Bisphosphonates (alendronate, zoledronic acid) are effective for HIV-associated osteoporosis using the same thresholds as the general population
• Weight-bearing exercise protects both bone density and cardiovascular health simultaneously

• HIV-Associated Neurocognitive Disorder (HAND): A spectrum of cognitive impairment ranging from asymptomatic neurocognitive impairment (ANI) to mild neurocognitive disorder (MND) to HIV-associated dementia (HAD, now rare with modern ART). Even with well-controlled HIV, approximately 15–30% of people have some degree of neurocognitive impairment, believed to be driven by residual neuroinflammation. Symptoms: slowed processing speed, memory difficulties, executive function impairment. Screening with the Montreal Cognitive Assessment (MoCA) is recommended for older HIV patients or those with cognitive complaints.
• Cancer risk in HIV: People with HIV have elevated risk of both AIDS-defining malignancies (ADCs) and non-AIDS-defining malignancies (NADCs). Effective ART has dramatically reduced ADC incidence, but NADCs remain elevated:
  • AIDS-defining cancers (with CD4 <200): Kaposi’s sarcoma, primary CNS lymphoma, invasive cervical cancer. ART dramatically reduces risk by restoring immunity.
  • Non-AIDS-defining cancers (elevated even with suppressed HIV): Anal cancer (40–80x increased risk in MSM), Hodgkin’s lymphoma (8x), liver cancer (with HBV/HCV coinfection), lung cancer (2–3x, compounded by high smoking rates), and HPV-related oropharyngeal cancer.
• Recommended screening: Anal Pap smear for MSM and women with anal intercourse history; HPV vaccination through age 45; hepatitis C treatment; annual low-dose CT chest for smokers 20+ pack-year history; routine age-appropriate colon, breast, and prostate cancer screening at standard thresholds.

Approximately 40% of people living with HIV experience depression at some point, compared to 7–17% in the general population. Anxiety disorders affect another 20–30%. The causes are multifactorial:

• Psychosocial burden: The shock of diagnosis, fear of disclosure, HIV-related stigma, grief over the pre-diagnosis life, uncertainty about the future, and the practical burdens of managing a chronic illness all contribute to depression and anxiety.
• Neurological effects: HIV itself (even when well-controlled with ART) may affect brain chemistry through neuroinflammation. ART medications, particularly efavirenz (EFV), can directly cause neuropsychiatric symptoms including depression, vivid dreams, dissociation, and suicidal ideation in a subset of patients — typically in the first 2–4 weeks of therapy. Switching from EFV to a newer INSTI-based regimen resolves these symptoms.
• Treatment: SSRIs (especially escitalopram and sertraline) are first-line antidepressants in HIV and are safe with most ART regimens. Check for drug interactions: fluoxetine and fluvoxamine inhibit CYP2D6 and can increase levels of some ART drugs. Bupropion is effective and generally safe but has minor interactions with some PIs. CBT is effective for both depression and anxiety in HIV and is particularly useful for addressing HIV-specific psychological challenges. Collaborative care models integrating mental health into HIV clinics significantly improve adherence and outcomes.
• Screening: PHQ-9 for depression and GAD-7 for anxiety should be administered at HIV diagnosis and at least annually thereafter in all people living with HIV.

• The weight of stigma: Internalized HIV stigma (self-stigma: believing you are shameful, contaminated, or deserving of suffering because of HIV) independently predicts depression, reduced ART adherence, and delayed care-seeking. HIV stigma is rooted in its historical association with marginalized communities and sexual transmission. Psychotherapy (particularly CBT and acceptance-based therapy), peer support groups, and community engagement programs reduce internalized stigma.
• Disclosure: Decisions about disclosing HIV status to sexual partners, family, friends, and employers involve complex trade-offs between health (U=U education, partner PrEP), legal obligations, and personal safety. In most US states, people with HIV have a legal obligation to disclose their status to sexual partners before engaging in activities with meaningful transmission risk; laws vary by state and evolve with U=U evidence. Organizations like The Well Project (for women), POZ Community, and local HIV community centers offer peer support and practical guidance on disclosure conversations.
• HIV and employment: The Americans with Disabilities Act (ADA) protects people with HIV from employment discrimination and requires reasonable accommodations (such as schedule flexibility for medical appointments). HIV status does not need to be disclosed to an employer in most circumstances. Only military service and some federal security clearances have specific HIV-related restrictions.

Vertical (perinatal) transmission of HIV from mother to child during pregnancy, labor/delivery, or breastfeeding is now virtually preventable with appropriate care. In the absence of any intervention, the risk of vertical transmission is approximately 15–45%. With optimal care, the risk can be reduced to less than 1%.

• ART in pregnancy: All pregnant women with HIV should receive combination ART regardless of CD4 count or viral load. The goal is to suppress viral load to undetectable before delivery. A woman with an undetectable viral load at delivery has a transmission risk below 0.1%. Starting ART early in pregnancy (first trimester if possible) and maintaining viral suppression throughout is the most important factor.
• Preferred ART in pregnancy: Integrase inhibitor-based regimens are now preferred in pregnancy. Dolutegravir (with TDF/FTC or TAF/FTC) is the most recommended first-line option per 2023 DHHS Perinatal HIV Guidelines. Early concerns about neural tube defects with dolutegravir periconception have been largely resolved by subsequent larger data; dolutegravir is now considered safe at conception and throughout pregnancy with appropriate counseling. Rilpivirine and efavirenz-based regimens are alternatives; lopinavir/ritonavir is less preferred due to tolerability.
• IV zidovudine during labor: For women with viral load >1,000 copies/mL near delivery (or unknown viral load), intrapartum IV zidovudine (AZT) reduces transmission risk. Women with viral load <50 copies/mL who are adherent to ART throughout pregnancy do NOT require IV AZT at delivery.
• Cesarean delivery: Scheduled C-section at 38 weeks is recommended for women with viral load ≥1,000 copies/mL near delivery. For women with undetectable viral load, mode of delivery is determined by obstetric indications alone — vaginal delivery is safe.
• Infant prophylaxis: All HIV-exposed infants receive ART prophylaxis after birth. Low-risk infants (mother virally suppressed) receive 4 weeks of zidovudine. Higher-risk infants receive 6 weeks of three-drug ART (zidovudine + lamivudine + nevirapine). Infants are tested for HIV at birth, 14–21 days, 1–2 months, and 4–6 months using PCR-based DNA/RNA tests (antibody tests are not valid until age 18 months due to maternal antibody transfer).
• Breastfeeding: In the US, Canada, and other resource-rich settings, women with HIV are advised NOT to breastfeed, as formula feeding eliminates breastfeeding transmission risk. This differs from guidance in resource-limited settings where breastfeeding risks (diarrhea, malnutrition) outweigh transmission risks if the mother is virally suppressed on ART.

Drug interactions between ART and hormonal contraception are clinically important and under-recognized. Several ART medications induce or inhibit CYP3A4 and other enzymes that metabolize estrogen and progestin, potentially reducing contraceptive efficacy or increasing side effects:

• ART drugs that REDUCE hormonal contraceptive efficacy (enzyme inducers): Efavirenz (EFV), nevirapine (NVP), and ritonavir (RTV, used as a pharmacokinetic booster) induce CYP3A4, which can reduce estrogen and progestin levels by 30–60%. Combined oral contraceptives (COCs) and progestin-only pills may fail; use barrier methods in addition, or switch to a non-interacting contraceptive method.
• ART drugs that INCREASE hormone levels: Cobicistat (a boosting agent in Biktarvy, Genvoya, Prezcobix) inhibits CYP3A4 and can increase progestin levels, potentially increasing side effects. Dolutegravir, bictegravir, and raltegravir (all INSTIs without boosters) have no significant hormonal contraceptive drug interactions.
• Safest contraceptive options for women on ART: IUDs (both hormonal and copper) are unaffected by ART, highly effective, and recommended as first-line. Depot medroxyprogesterone acetate (DMPA, Depo-Provera) has minimal interaction with most ART. Long-acting implants (etonogestrel, Nexplanon) may have reduced efficacy with enzyme-inducing ART; discuss with your HIV provider and OB/GYN.

PrEP reduces the risk of HIV from sex by more than 99% and from injection drug use by more than 74% when taken consistently. Three PrEP options are FDA-approved in the US:

• Truvada (TDF/FTC, emtricitabine/tenofovir DF): The original oral PrEP, approved 2012. Once daily. Highly effective for all populations. Older kidney and bone safety profile than TAF-based PrEP; monitor renal function. Generic TDF/FTC now widely available at low or no cost with assistance programs.
• Descovy (TAF/FTC, emtricitabine/tenofovir AF): Approved 2019 for cisgender men and transgender women who have sex with men. Better renal and bone safety than Truvada. NOT approved for people assigned female at birth for penile-vaginal sex (insufficient data in trials). Once daily.
• Apretude (cabotegravir injection): Long-acting injectable PrEP, approved 2021. Given every 2 months by a healthcare provider. Shown to be superior to daily oral Truvada in the HPTN 083 (cisgender men and transgender women) and HPTN 084 (cisgender women in sub-Saharan Africa) trials. Eliminates daily pill-taking; ideal for people who have adherence challenges with daily oral medications. Requires healthcare provider visits every 8 weeks.

Who qualifies for PrEP? PrEP is recommended for HIV-negative individuals with substantial HIV risk, including: people with an HIV-positive sexual partner; people who have had an STI in the past 6 months; people who do not consistently use condoms with partners of unknown or positive HIV status; and people who inject drugs and share equipment.

PrEP access: PrEP is available through HIV clinics, primary care providers, sexual health clinics, and Planned Parenthood locations. The federal "Ready, Set, PrEP" program provides free PrEP to qualifying uninsured Americans. GoodRx and generic programs offer Truvada generics for <$30/month.

• PEP (Post-Exposure Prophylaxis): A 28-day course of ART started within 72 hours of a potential HIV exposure (sexual exposure, needle sharing, needlestick) to prevent HIV infection. PEP is highly effective if started promptly; efficacy decreases after 72 hours and is zero after 72 hours (it does not work as a substitute for PrEP). Available at emergency rooms, urgent care centers, and HIV clinics. Cost-free for uninsured through many jurisdictional programs.
• Condoms: Male latex condoms reduce HIV transmission by approximately 70% with consistent use; female condoms provide similar protection. Condoms also protect against other STIs (gonorrhea, chlamydia, syphilis, herpes, HPV) that PrEP does not cover. Used in combination with PrEP, condoms provide near-complete protection.
• Harm reduction for people who inject drugs: Syringe service programs (SSPs, formerly called needle exchange programs) provide sterile syringes and other equipment, preventing HIV transmission through shared needles. Naloxone distribution through SSPs also prevents opioid overdose deaths. Evidence from decades of research shows SSPs reduce HIV transmission, do not increase drug use, and serve as entry points to treatment services.
• Substance use and HIV risk: Methamphetamine and alcohol use are strongly associated with HIV risk through impaired decision-making and sexual risk behaviors. Treating substance use disorders reduces HIV incidence. Buprenorphine for opioid use disorder, naltrexone for alcohol use disorder, and contingency management programs for methamphetamine are all evidence-based and should be integrated into HIV prevention and care.

HIV antiretrovirals target specific steps in the HIV life cycle. Understanding which step each drug targets helps explain why combination therapy (at least 2–3 drugs from 2+ drug classes) is necessary to prevent resistance:

• Integrase Strand Transfer Inhibitors (INSTIs): The cornerstone of modern first-line HIV therapy. INSTIs block the HIV integrase enzyme that inserts viral DNA into the host cell’s chromosome. The newest INSTIs — bictegravir (in Biktarvy), dolutegravir (in Triumeq, Dovato), and cabotegravir (in Apretude, Cabenuva) — have a high genetic barrier to resistance, excellent tolerability, and few drug interactions. Dolutegravir-based regimens are now recommended by WHO for first-line therapy globally; bictegravir-based regimens (Biktarvy: bictegravir/tenofovir AF/emtricitabine) are the most prescribed first-line regimen in the United States.
• Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs): The "backbone" of most ART regimens. NRTIs are incorporated into the viral DNA chain during reverse transcription, causing chain termination and blocking HIV replication. Most modern regimens include 2 NRTIs. Tenofovir alafenamide (TAF, with improved renal and bone safety compared to older tenofovir disoproxil fumarate/TDF) combined with emtricitabine (FTC) is the dominant NRTI backbone.
• Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Block reverse transcriptase directly (different binding site from NRTIs). Efavirenz (EFV) was the dominant first-line agent for years but is now largely replaced by INSTIs due to CNS side effects (vivid dreams, dizziness). Rilpivirine (RPV, in Odefsey, Complera) is an NNRTI with an excellent tolerability profile; it requires a food requirement and has a drug interaction with proton pump inhibitors.
• Protease Inhibitors (PIs): Block HIV protease, which is required to cleave viral polyproteins into functional viral proteins. Now used primarily in second-line regimens or in combination with pharmacokinetic boosters (ritonavir, cobicistat) when resistance to first-line INSTIs occurs. Darunavir (DRV) is the most used PI in resource-rich settings.
• Entry inhibitors: Block HIV from entering CD4+ T cells. Includes fusion inhibitors (enfuvirtide — injectable, reserved for salvage), CCR5 antagonists (maraviroc — only for R5-tropic virus, requires tropism testing), and CD4 post-attachment inhibitors (ibalizumab — IV monthly, for multidrug-resistant HIV).
• Long-acting injectable ART: Cabotegravir + rilpivirine (Cabenuva) is an FDA-approved monthly or every-other-month injectable regimen that eliminates daily pills entirely. It is an option for virologically suppressed adults without prior NNRTI or INSTI resistance. The FDA also approved lenacapavir (Sunlenca), a 6-month injection for heavily treatment-experienced patients with multidrug-resistant HIV.

• Primary goal: Achieve and maintain an undetectable viral load (HIV RNA <20–50 copies/mL depending on assay threshold) within 3–6 months of starting ART
• U=U (Undetectable = Untransmittable): When viral load is undetectable and sustained on ART, there is effectively ZERO risk of sexually transmitting HIV to a partner. This is one of the most important public health messages in modern HIV medicine, established by the PARTNER and HPTN 052 studies.
• CD4 count recovery: CD4+ T cells typically increase by 100–200 cells/μL in the first year on effective ART, then continue to rise more slowly. Most patients eventually reach normal CD4 counts (>500 cells/μL) with sustained viral suppression. CD4 count below 200 cells/μL defines AIDS.
• Monitoring schedule: Viral load at 4–8 weeks after starting ART, then every 3–6 months until suppressed, then every 6 months once stably suppressed. CD4 count monitoring can be extended to annually (or less frequently) once suppressed with CD4 >500 cells/μL.
• Adherence: ART must be taken consistently — missing doses allows viral replication, which can lead to resistance mutations that reduce future drug options. Modern INSTI-based regimens are more forgiving than older regimens in terms of adherence thresholds, but consistent daily dosing remains the standard. Pharmacist consultation, pill reminder apps, and blister packs with calendars help adherence.