What is the typical treatment regimen for managing HIV?

Management of HIV

When to Initiate Treatment

Start antiretroviral therapy (ART) immediately upon HIV diagnosis, ideally at the first clinic visit or within 7 days, regardless of CD4 count or viral load. 1, 2

• Same-day ART initiation is feasible and recommended when resources permit, as it increases care retention and population-level viral suppression. 2
• For acute HIV infection, immediate ART is mandatory due to the urgent need for viral suppression. 3, 2
• Treatment should begin regardless of CD4 cell count or viral load to prevent disease progression, improve clinical outcomes, and limit transmission. 1

Recommended First-Line Regimens

The preferred initial regimen consists of an integrase strand transfer inhibitor (InSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs). 1, 2

Specific Recommended Combinations (in order of preference):

• Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) - single tablet, once daily 1
• Dolutegravir plus tenofovir alafenamide (or tenofovir disoproxil fumarate)/emtricitabine 1, 2
• Dolutegravir/lamivudine - a 2-drug regimen option 3
• Raltegravir plus TAF/emtricitabine 2

Why InSTIs Are Preferred:

• Dolutegravir and bictegravir have comparable high rates of viral suppression, minimal toxicity, low risk of drug interactions, and high barrier to resistance. 3
• InSTI-based regimens achieve faster viral suppression (typically within 24 weeks) compared to other drug classes. 1
• Raltegravir is less favored due to higher pill burden (≥3 pills per day) and lower barrier to resistance. 3
• Elvitegravir is the least-favored InSTI because the co-formulated cobicistat causes more drug interactions. 3

NRTI Backbone Considerations:

• Tenofovir alafenamide (TAF) is preferred over tenofovir disoproxil fumarate (TDF) due to fewer renal and bone toxicities. 3
• TDF has lipid-lowering effects (clinical significance unknown) and should be avoided or dose-adjusted if creatinine clearance is below 60 mL/min. 3, 4
• Emtricitabine and lamivudine have comparable efficacy and are interchangeable. 4, 5

Required Baseline Testing Before Starting ART

Obtain the following tests before initiating therapy: 1

• CD4+ cell count
• HIV RNA level (viral load)
• HIV genotype resistance testing
• HLA-B*5701 testing if considering abacavir - those who test positive must not receive abacavir 1, 2
• Hepatitis B surface antigen
• Hepatitis C antibody
• Basic chemistry panel including serum creatinine
• Liver function tests

Monitoring After Treatment Initiation

Assess viral load 4-6 weeks after starting ART to evaluate initial response and adherence. 1, 2

• After initial suppression, monitor viral load every 3 months until suppressed (<50 copies/mL) for at least 1 year, then every 6 months if adherence is consistent. 2
• Monitor CD4 cell count every 6 months until counts are above 250/μL for at least 1 year with viral suppression. 2
• HIV RNA suppression typically occurs within 24 weeks, faster with InSTI-based regimens. 1

Special Clinical Situations

Active Opportunistic Infections:

• Most opportunistic infections: Start ART within 2 weeks after initiating treatment for the opportunistic infection. 3
• Tuberculosis with CD4 <50 cells/μL: Start ART within 2 weeks after tuberculosis treatment initiation (when tuberculosis meningitis is not suspected). 3
• Tuberculosis with higher CD4 counts: Start ART within 2-8 weeks after starting tuberculosis treatment. 3
• Cryptococcal meningitis: Start ART 4-6 weeks after starting antifungal therapy. 3, 2
• Tuberculosis meningitis: Most experts recommend starting ART within 2 weeks with close monitoring for patients with CD4 <50 cells/μL. 3

Cancer Diagnosis:

• Immediate ART initiation is recommended with special attention to drug-drug interactions and monitoring for early ART adverse events. 3, 2

Pregnancy:

• Dolutegravir is recommended for pregnant women combined with tenofovir/emtricitabine or lamivudine. 1

Managing Virologic Failure

Virologic failure is defined as HIV RNA >200 copies/mL and should be confirmed with repeat testing. 1

• Obtain resistance testing while the patient is taking the failing regimen or within 4 weeks of stopping ART. 1
• If viral load has not declined after starting ART, assess adherence and medication tolerability first. 2
• If adherence appears sufficient but viral suppression is not achieved, obtain genotypic resistance testing. 2

Switching Regimens:

• Review complete ART history, prior resistance testing results, tolerability, co-medications, and cost before making changes. 1
• For failure of NNRTI-based regimens, dolutegravir plus active NRTIs is superior to protease inhibitor-based regimens. 4
• For failure of InSTI-based regimens, boosted protease inhibitor with active NRTIs is recommended. 4

Adherence Support Strategies

Systematic monitoring of ART adherence is crucial for successful treatment. 2

• Integration of directly observed ART in methadone maintenance programs is recommended for persons with substance use disorders. 3, 2
• Screen for and address housing instability, food insecurity, ongoing substance use, psychiatric disorders, medication adverse effects, and pill burden. 3
• Opioid substitution therapy for opioid-dependent patients is recommended. 3

Expected Clinical Outcomes

With effective modern ART regimens, survival rates among HIV-infected adults retained in care approach those of uninfected adults. 1, 2

• Current regimens can sustain HIV suppression and prevent new HIV infections when used effectively. 1
• The lifespan of people with HIV is increasing and approaches that of people without HIV. 3

Important Caveats

Drug-Drug Interactions:

• Pharmacological boosters (ritonavir and cobicistat) cause significant drug-drug interactions and should be avoided when possible. 3
• Review all concomitant medications before selecting an ART regimen. 3

Weight Gain:

• Tenofovir alafenamide is associated with greater weight gain than tenofovir disoproxil fumarate. 3

Aging Population:

• Older persons with HIV are at increased risk of cardiovascular disease, chronic kidney disease, neurocognitive impairment, and mental health disorders despite achieving durable viral suppression. 3
• Polypharmacy occurs earlier in people with HIV than in those without HIV. 3