Treatment of HIV in Adults
Initiate antiretroviral therapy (ART) immediately upon HIV diagnosis with a recommended integrase strand transfer inhibitor (INSTI)-based regimen, prioritizing single-tablet formulations for optimal adherence and virological suppression. 1
Recommended Initial ART Regimens
The following regimens represent first-line options for treatment-naïve adults with HIV-1 infection:
Primary Recommended Regimens
Single-tablet regimens are strongly preferred as they improve adherence and simplify treatment 1:
- Bictegravir/tenofovir alafenamide/emtricitabine (evidence rating: AIa) 1
- Dolutegravir/abacavir/lamivudine - use only if HLA-B*5701 negative (evidence rating: AIa) 1
- Dolutegravir/tenofovir alafenamide/emtricitabine (evidence rating: AIa) 1
Alternative Recommended Regimens
When primary regimens are contraindicated or not tolerated 1:
- Darunavir/cobicistat/tenofovir alafenamide/emtricitabine - particularly useful for suspected multidrug resistance 1
- Dolutegravir plus tenofovir disoproxil fumarate/lamivudine - for patients at high risk of poor adherence 1
- Raltegravir plus tenofovir alafenamide/emtricitabine - for patients with high risk of drug-drug interactions 1
- Efavirenz (400-600 mg) plus tenofovir disoproxil fumarate/emtricitabine - for HIV/tuberculosis co-infection or pregnancy 1
Special Population Considerations
Pregnancy and Reproductive Planning
- Efavirenz-based regimens are appropriate for patients who are pregnant or intend to become pregnant 1
- Raltegravir plus tenofovir disoproxil fumarate/lamivudine for patients with child-bearing potential trying to conceive 1
Renal Impairment
- Avoid tenofovir disoproxil fumarate if creatinine clearance <60 mL/min 2
- Use dolutegravir/abacavir/lamivudine with caution in kidney insufficiency 1
- Tenofovir alafenamide-based regimens are preferred over tenofovir disoproxil fumarate for renal protection 2
Suspected Drug Resistance
- Darunavir-based regimens have high barrier to resistance and are preferred for known or suspected pretherapy multidrug resistance 1
Management of Virological Failure
Resistance Testing and Regimen Switching
Obtain resistance testing while the patient remains on the failing regimen (or within 4 weeks of stopping) before making any treatment changes 1:
- Virological failure is defined as HIV RNA >200 copies/mL and should be confirmed before switching 1
- Never add a single active agent to a failing regimen 1
Specific Failure Scenarios
After NNRTI failure: Use dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (nRTIs) with ≥1 active drug determined by genotypic testing 1
After INSTI failure: Use a boosted protease inhibitor plus 2 nRTIs with ≥1 active nRTI 1
After raltegravir or elvitegravir resistance: Use dolutegravir dosed twice daily plus at least 1 fully active agent 1
Multiclass (3-class) resistance: Construct the next regimen using drugs from new classes such as fostemsavir or ibalizumab with at least 1 additional active drug in an optimized ART regimen 1
Switching Regimens in Virologically Suppressed Patients
In patients with sustained viral suppression, switching from a 3-drug to a 2-drug regimen is appropriate to manage toxicity, intolerance, adherence issues, or patient preference, provided both agents are fully active 1:
Recommended 2-Drug Regimens
- Dolutegravir/rilpivirine (evidence rating: AIa) 1
- Boosted protease inhibitor with lamivudine (evidence rating: AIa) 1
- Dolutegravir/lamivudine (evidence rating: AIa) 1
- Long-acting injectable cabotegravir and rilpivirine every 4 weeks (evidence rating: AIa) or every 8 weeks (evidence rating: BIb) 1
Critical Contraindications for Switching
- Do not switch from a boosted protease inhibitor to a regimen with low genetic barrier to resistance (NNRTI or raltegravir) in patients with nRTI resistance mutations 1
- Monotherapy with boosted protease inhibitors or dolutegravir is not recommended 1
Special Considerations for Hepatitis B Co-infection
Patients with chronic hepatitis B must continue tenofovir (alafenamide or disoproxil fumarate) to maintain HBV suppression when switching HIV regimens 1, 2:
- Switching to regimens containing only lamivudine or emtricitabine without tenofovir will not maintain HBV suppression 1
- Risk of severe hepatitis flare or hepatic decompensation exists if tenofovir is discontinued, particularly in patients with cirrhosis 2
- Alternative HBV suppressive therapy is required if tenofovir must be discontinued 1
Management of Older Adults with HIV
Polypharmacy and Frailty Assessment
Close and sustained attention to polypharmacy is mandatory in older people with HIV 1:
- Assess mobility and frailty in all patients ≥50 years using a validated frailty assessment tool 1
- Frequency of assessment: every 1-2 years for frail/prefrail patients; up to every 5 years for robust patients 1
- For frail or prefrail patients: manage polypharmacy, refer for complete geriatric assessment, prescribe exercise and physical therapy, and provide nutrition advice 1
Cognitive Function Screening
Routine cognitive function assessment every 2 years using a validated instrument is recommended for people with HIV older than 60 years 1
Common Pitfalls and Caveats
Drug-Drug Interactions
- Review all co-medications to ensure no dosing adjustments are needed, particularly with tenofovir alafenamide 1
- Certain medications require dose modification when co-administered with antiretrovirals 2
Adherence Optimization
- Single-tablet regimens significantly improve adherence compared to multi-tablet regimens 3, 4
- Virological failure with protease inhibitors is rare and usually reflects adherence issues rather than resistance; support adherence or switch to a more tolerable regimen 1
Baseline Testing Requirements
Before initiating ART, obtain 5:
- HIV-1 RNA level and CD4+ count
- Resistance testing (genotypic)
- HLA-B*5701 testing (if considering abacavir)
- Hepatitis B surface antigen and hepatitis C antibody
- Serum creatinine and estimated creatinine clearance
- Pregnancy test for individuals of childbearing potential