What is the recommended treatment for Human Immunodeficiency Virus (HIV) in adults and pregnant individuals?

HIV Treatment in Adults and Pregnancy

Immediate ART Initiation

Start antiretroviral therapy (ART) as soon as possible after HIV diagnosis, ideally at the first clinic visit if the patient is ready to commit to treatment. 1, 2, 3

• Remove all structural barriers that delay ART receipt to enable same-day initiation when clinically appropriate 1, 4
• Rapid ART initiation (within 7 days) using integrase strand transfer inhibitor (InSTI)-based regimens is the standard of care 2, 3
• Treatment should begin regardless of CD4 count or viral load to prevent disease progression, improve clinical outcomes, and limit transmission 3

First-Line Regimens for Adults

Preferred Initial Regimens (Listed Alphabetically)

The following InSTI-based three-drug regimens are recommended with the highest evidence ratings (AIa):

• Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) 1, 2, 3
• Dolutegravir plus tenofovir alafenamide (or tenofovir disoproxil fumarate)/emtricitabine or lamivudine 1, 2, 3
• Dolutegravir/abacavir/lamivudine (requires HLA-B*5701 testing first; avoid if positive) 1, 2

Important Considerations for Tenofovir Selection

• Tenofovir alafenamide (TAF) is preferred over tenofovir disoproxil fumarate (TDF) due to fewer renal and bone toxicities 3
• Avoid TDF in patients with or at risk for kidney disease (creatinine clearance <60 mL/min) or bone disease (osteopenia/osteoporosis) 1, 5
• TDF has lipid-lowering effects and requires dose adjustment if creatinine clearance is below 60 mL/min 3, 5

Baseline Testing Required Before ART Initiation

Obtain the following tests before starting therapy:

• CD4+ cell count and HIV RNA level 3, 4
• HIV genotype resistance testing 3, 4
• HLA-B*5701 testing if considering abacavir-containing regimens 1, 3
• Hepatitis B surface antigen and hepatitis C antibody 3, 4
• Basic chemistry panel including serum creatinine, estimated creatinine clearance 3, 5
• Liver function tests 3, 4
• Urine glucose and urine protein; serum phosphorus if chronic kidney disease present 5

Treatment During Pregnancy

Recommended Regimens for Pregnant Women

The following regimens are recommended during pregnancy, all combined with tenofovir disoproxil fumarate/emtricitabine or tenofovir disoproxil fumarate/lamivudine:

• Dolutegravir (evidence rating AIb) - preferred option 1, 2, 3
• Atazanavir/ritonavir (evidence rating AIIa) 1
• Darunavir/ritonavir (evidence rating AIIa) 1
• Raltegravir (evidence rating AIIa) 1
• Efavirenz (evidence rating BIa) 1

Key Pregnancy Considerations

• Dolutegravir plus tenofovir alafenamide/emtricitabine is also supported during pregnancy (evidence rating AIb) 1
• Women already taking effective ART when they become pregnant do not necessarily need to switch regimens 1
• Pregnant individuals should initiate ART for their own health and to reduce mother-to-child transmission 1, 6
• ART initiated between 28-36 weeks gestation significantly reduces infant HIV transmission or death compared to short-course regimens 6

Pregnancy-Specific Adverse Events to Monitor

• Increased risk of prematurity with certain protease inhibitor-based regimens 6
• Higher rates of low birth weight when ART started at 24 weeks compared to later initiation 6
• Monitor for maternal severe adverse events, particularly with nevirapine-based regimens 6

Special Situations: Modified Timing for ART Initiation

Opportunistic Infections

For most opportunistic infections, initiate ART within 2 weeks of starting treatment for the infection 1, 2, 4

Tuberculosis

• If CD4 count ≥50/μL: Initiate ART within 2-8 weeks of starting TB treatment 1, 2, 4
• If CD4 count <50/μL: Initiate ART within 2 weeks of starting TB treatment 2
• Recommended regimens with rifamycin-based TB treatment:
  • Dolutegravir 50 mg twice daily plus 2 NRTIs 1
  • Efavirenz 600 mg daily plus 2 NRTIs 1
  • Raltegravir 800 mg twice daily plus 2 NRTIs 1
• Avoid bictegravir with rifampin due to drug-drug interactions 1
• Boosted protease inhibitors should only be used if InSTI-based or efavirenz-based regimens are not options; substitute rifabutin 150 mg daily for rifampin if protease inhibitor must be used 1

Cryptococcal Meningitis

• Initiate ART 4-6 weeks after starting antifungal therapy 1
• Earlier initiation at 2 weeks may be considered for those who have clinically improved with controlled intracranial pressure 2, 4

Cancer Diagnosis

• Initiate ART immediately with attention to drug-drug interactions 1

Monitoring After ART Initiation

Viral Load Monitoring Schedule

• Assess viral load 4-6 weeks after starting ART to evaluate initial response and adherence 3, 4
• HIV RNA suppression typically occurs within 24 weeks, faster with InSTI-based regimens (often by 12 weeks) 3, 7
• Once viral suppression is achieved, monitor every 3 months until suppression is maintained for at least 1 year 4
• After 1 year of viral suppression, monitoring can be reduced to every 6 months 4

Expected Outcomes

• Integrase inhibitor-based regimens achieve significantly shorter time to viral suppression compared to protease inhibitor-based regimens 7
• Among patients initiating ART at first visit: 79% achieve viral suppression at week 12,82% at week 24, and 88% at week 48 7
• With effective modern ART regimens, survival rates among HIV-infected adults retained in care approach those of uninfected adults 2, 3

Common Pitfalls and Caveats

Rapid Start Contraindications

• Do not use rapid start protocols for patients requiring baseline laboratory review, those with chronic hepatitis B, HIV RNA >500,000 copies/mL, possibly CD4 <200/μL, or those being treated for active opportunistic infections 1
• HLA-B*5701 testing typically takes several days; use tenofovir-containing regimens for same-day starts until results available 1

Drug-Drug Interactions

• Pharmacological boosters (ritonavir and cobicistat) cause significant drug-drug interactions and should be avoided when possible 3
• Review all comedications before initiating ART, particularly in cancer patients 1

Hepatitis B Co-infection

• Test all patients for HBV before initiating ART 3, 5
• Severe acute exacerbations of hepatitis B can occur if tenofovir is discontinued; monitor hepatic function closely for several months after stopping anti-HBV therapy 5
• Tenofovir disoproxil fumarate alone should not be used in patients with HIV-1 infection 5

Patient Readiness and Support

• Newly diagnosed patients often feel traumatized and overwhelmed by HIV diagnosis, creating difficulty accepting HIV status 8
• Fear of lifelong medication and severe side effects in the immediate period after initiating ART can lead to adherence challenges 8
• Address housing instability, food insecurity, ongoing substance use, psychiatric disorders, medication adverse effects, and pill burden to support ART adherence 3
• Visible signals of HIV status (taking medications, attending appointments) remain highly stigmatizing despite patient enthusiasm for treatment benefits 8

Cardiovascular and Comorbidity Considerations

• Avoid abacavir-containing regimens in patients with or at high risk for cardiovascular disease; use tenofovir-containing regimens instead 1
• 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