What are the recommended initial and second-line treatment regimens for HIV?

HIV Treatment Guidelines

All HIV-infected individuals with detectable plasma virus should receive antiretroviral therapy (ART) immediately upon diagnosis, regardless of CD4 cell count, with an integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) as the preferred initial regimen. 1, 2, 3

When to Initiate Treatment

• Start ART immediately after HIV diagnosis, including at the first clinic visit if the patient is ready to commit to treatment 3
• Treatment is recommended for all viremic patients with established HIV infection, regardless of CD4 cell count 4
• In acute HIV infection, initiate ART as soon as possible 4, 3
• Baseline resistance testing is mandatory before initiating therapy, though treatment may begin before results are available 1, 3

Preferred First-Line Regimens

The following InSTI-based regimens are recommended as first-line therapy (listed in order of preference based on most recent guidelines):

Top-Tier Preferred Regimens

• Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) - preferred for most patients due to high efficacy, favorable side effect profile, and high barrier to resistance 2, 3
• Dolutegravir plus tenofovir alafenamide/emtricitabine (DTG + TAF/FTC) - highly effective with strong resistance profile 1, 2, 3
• Dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) - effective but requires mandatory HLA-B*5701 testing before use 4, 1, 2, 3

Additional Recommended InSTI-Based Regimens

• Elvitegravir/cobicistat/TAF/emtricitabine 4
• Raltegravir plus TAF/emtricitabine 4

Two-Drug Regimen (Limited Use)

• Dolutegravir/lamivudine (DTG/3TC) - recommended ONLY if all of the following criteria are met: HIV RNA <500,000 copies/mL, no lamivudine resistance, and no hepatitis B co-infection 2, 5, 6

Alternative Regimens When InSTI Not an Option

If an InSTI cannot be used (e.g., after exposure to long-acting cabotegravir as PrEP):

• Darunavir (boosted with ritonavir or cobicistat) plus TAF/FTC or abacavir/lamivudine 4, 2
• Efavirenz/TDF/emtricitabine 4
• Rilpivirine/TAF (or TDF)/emtricitabine 4

Critical Pre-Treatment Requirements

Mandatory Testing

• HLA-B*5701 testing must be performed before prescribing any abacavir-containing regimen - approximately 50% of HLA-B*5701-positive individuals will experience potentially life-threatening hypersensitivity reactions 4, 1, 2, 3
• Those who test positive for HLA-B*5701 should never receive abacavir 4
• Baseline resistance testing should be obtained 1, 3

Special Population Considerations

Renal Impairment

• Avoid tenofovir disoproxil fumarate (TDF)-containing regimens in patients with or at risk for kidney disease 4, 2, 3
• TDF should be avoided or dose-adjusted in patients with creatinine clearance <60 mL/min 4
• TAF is not recommended in patients with creatinine clearance <30 mL/min 4

Bone Disease

• Prefer TAF over TDF for patients with osteopenia or osteoporosis 4, 2, 3
• TAF has fewer renal and bone toxicities compared to TDF, especially when used with pharmacological boosters 1, 2

Hepatitis B Co-infection

• Use regimens containing TAF or TDF plus lamivudine or emtricitabine 4, 2, 3
• Avoid DTG/3TC two-drug regimen in HBV co-infection 2
• Entecavir may be used to treat HBV but should be avoided if HIV RNA is not suppressed, as it can select for drug-resistant HIV 4

Hepatitis C Co-infection

• Start an ART regimen with drugs that do not have significant drug interactions with HCV therapies 4

Pregnancy

• DTG plus TAF/FTC is the recommended regimen 2, 3
• BIC/TAF/FTC is an alternative 2
• HIV-infected pregnant women should initiate ART for their own health and to reduce HIV transmission to their infant 4

High Viral Load or Low CD4 Count

• Patients with high viral load or low CD4 count require potent regimens, as some combinations have suboptimal virologic suppression in this setting 1
• Limited data exists for DTG/3TC in patients with CD4 counts <200/mm³ 5

Monitoring After Treatment Initiation

Viral Load Monitoring

• Measure viral load 4-6 weeks after starting ART to assess initial response 2, 3
• Once viral suppression is achieved, monitor every 3 months until suppression is maintained for at least 1 year 2
• After 1 year of viral suppression, monitoring can be reduced to every 6 months 2
• Regular viral load monitoring is essential to identify treatment failures early and minimize resistance development 4, 1

Toxicity Monitoring

• Monitor for development of kidney disease with estimated glomerular filtration rate, urinalysis, and testing for glycosuria and albuminuria or proteinuria when ART is initiated or changed and every 6 months 4
• Regularly assess for drug-specific toxicities, particularly during the first few months of therapy 1
• Discontinue TDF or TAF if renal function worsens 4

Adherence Assessment

• Assess adherence at each visit, as this is critical for treatment success 1

Common Pitfalls to Avoid

• Not testing for HLA-B*5701 before prescribing abacavir can lead to potentially life-threatening hypersensitivity reactions 1, 2, 3
• Starting DTG/3TC without confirming HIV RNA level, resistance status, and HBV status 2
• Overlooking drug interactions, particularly with cobicistat-boosted regimens (EVG/c, DRV/c) or in patients taking rifampin 2
• Delaying ART initiation leads to poorer outcomes; treatment should be started as soon as possible after diagnosis 1, 2
• Using two-drug regimens inappropriately - no current two-drug regimen is recommended for people with chronic hepatitis B virus as none include tenofovir 6
• Planned discontinuation of early ART after a specific duration is not recommended outside a research setting 4

Drug Interaction Considerations

• Cobicistat-boosted regimens have more drug interactions 2
• Rifampin cannot be used with many regimens including BIC/TAF/FTC, DTG/3TC, EVG/COBI, and rilpivirine 2