How should HIV infection be managed in both adults and children, including timing of antiretroviral therapy initiation, first‑line regimens by weight, cotrimoxazole prophylaxis, tuberculosis screening, viral load monitoring, and second‑line therapy for virologic failure?

HIV/AIDS Management in Adults and Children

Timing of Antiretroviral Therapy Initiation

Start antiretroviral therapy (ART) immediately upon HIV diagnosis—ideally on the same day or within 7 days—regardless of CD4 count, viral load, or age, unless the patient is not ready to commit to treatment. 1, 2, 3

Adults

• Immediate or same-day ART initiation is strongly recommended for all newly diagnosed adults, as it reduces mortality by 74%, improves viral suppression rates, accelerates time to viral suppression, and enhances retention in care 2, 3, 4
• Remove structural barriers (staffing, drug availability, insurance) to enable ART start at the first clinic visit 1, 3
• Draw baseline labs (HIV-1 RNA, CD4 count, genotype resistance testing, HLA-B*5701, hepatitis serology, CBC, CMP, lipids, glucose, urinalysis) before starting ART, but do not delay treatment while waiting for results 1, 2, 3
• The only exception: HLA-B*5701 results must be available before using abacavir-containing regimens 1, 2

Children

• All HIV-infected infants under 12 months must start ART immediately after confirmed diagnosis, regardless of clinical status, CD4 count, or viral load, as this age group has the highest risk of rapid disease progression 5
• Diagnosis in infants requires PCR of HIV DNA: first test before 48 hours of life (38% sensitivity), second test at 1-2 months (93% sensitivity), and third test at 3-6 months; two positive tests on separate samples confirm infection 5

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First-Line ART Regimens

Adults: Preferred Regimens (Listed by Priority)

The top-tier regimens are integrase strand transfer inhibitor (InSTI)-based combinations with two nucleoside reverse transcriptase inhibitors (NRTIs): 1, 2

1. Bictegravir/tenofovir alafenamide (TAF)/emtricitabine – preferred for most patients due to high barrier to resistance, minimal drug interactions, once-daily dosing, and excellent tolerability 1, 2

2. Dolutegravir plus TAF/emtricitabine – equally recommended with excellent efficacy and favorable renal/bone safety profile compared to tenofovir disoproxil fumarate (TDF) 1, 2

3. Dolutegravir/abacavir/lamivudine – requires negative HLA-B*5701 testing; avoid in patients with cardiovascular disease risk (use tenofovir-containing regimen instead) 1

Adults: Alternative Regimens When Preferred Options Unavailable

• Darunavir/cobicistat or darunavir/ritonavir plus TAF (or TDF)/emtricitabine 1
• Raltegravir plus TAF/emtricitabine (higher pill burden, lower resistance barrier than dolutegravir/bictegravir) 1
• Rilpivirine/TAF/emtricitabine (only if baseline HIV RNA <100,000 copies/mL and CD4 >200/μL) 1
• Efavirenz/TDF/emtricitabine 1

Adults: Regimens for Rapid/Same-Day Start

For rapid ART initiation, avoid NNRTIs and abacavir due to requirements for baseline testing (HLA-B*5701 for abacavir takes several days) 1, 3

Use tenofovir-containing regimens with InSTIs: 3

• Bictegravir/TAF/emtricitabine
• Dolutegravir plus TAF/emtricitabine
• Raltegravir plus TAF or TDF/emtricitabine

Children: Weight-Based Regimens

Pediatric regimens should include at least three antiretroviral drugs: two NRTIs plus a protease inhibitor 5

• Treatment goals include reducing HIV RNA to undetectable levels, preserving immune function, delaying disease progression, and improving survival 5

Special Considerations

• Avoid TDF in patients with or at risk for kidney disease or bone disease (osteopenia/osteoporosis); use TAF instead 1, 2
• Pregnant patients should receive darunavir 600 mg with ritonavir 100 mg twice daily (not once-daily), or bictegravir/dolutegravir-based regimens 2
• Note interim reports of potential dolutegravir teratogenicity when initiated before conception; however, it remains acceptable in pregnancy 1, 2
• Two-drug regimens (dolutegravir/lamivudine) are only recommended when patients cannot take abacavir, TAF, or TDF 1

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Cotrimoxazole (Trimethoprim-Sulfamethoxazole) Prophylaxis

Adults

Start primary Pneumocystis pneumonia (PCP) prophylaxis with trimethoprim-sulfamethoxazole for all patients with CD4 <200 cells/μL 1, 2, 3

• Continue prophylaxis even after starting ART until CD4 rises above 200 cells/μL for at least 3 months 2
• Do not start primary Mycobacterium avium complex (MAC) prophylaxis if effective ART is initiated immediately, as MAC incidence with early ART is sufficiently low 1, 2, 3
• Cryptococcal prophylaxis is not recommended in high-resource settings with low disease prevalence 1, 3
• In resource-limited settings with high HIV prevalence, cotrimoxazole prophylaxis for all adults with tuberculosis (regardless of HIV status) reduces 6-month mortality by 29% 6

Children

All HIV-exposed infants should start PCP prophylaxis at 4-6 weeks of age and continue until HIV infection is ruled out 5

Age-specific CD4 thresholds for PCP prophylaxis in HIV-infected children: 5

• <12 months: CD4 <750 cells/mm³ or <15%
• 1-5 years: CD4 <500 cells/mm³ or <15%
• ≥6 years: CD4 <200 cells/mm³ or <15%

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Tuberculosis Screening and ART Timing with Active TB

Adults with TB Coinfection

ART timing depends on CD4 count and type of TB: 1, 3, 7

• CD4 <50 cells/μL (non-meningeal TB): Start ART within 2 weeks of TB treatment initiation 1, 3, 7
• CD4 ≥50 cells/μL: Start ART within 2-8 weeks of TB treatment initiation 1, 3, 7
• TB meningitis: Timing remains controversial; most experts recommend starting ART within 2 weeks with close monitoring for patients with CD4 <50 cells/μL 1
• Cryptococcal meningitis: Delay ART for 4-6 weeks after starting antifungal therapy 1, 3

Key evidence: Among patients with CD4 ≤50 cells/mm³, earlier ART (≤4 weeks) reduced risk of death by 6% (absolute risk difference), but increased IRIS risk by 6% 7. For patients with higher CD4 counts, earlier ART did not alter mortality but reduced AIDS-defining events 7.

Other Opportunistic Infections

For most opportunistic infections, start ART within 2 weeks of beginning OI treatment 1, 3

• For newly diagnosed malignancy, start ART immediately with attention to drug-drug interactions 1, 3

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Viral Load Monitoring

Adults

Monitor HIV RNA (viral load) at 4-6 weeks after starting ART, then every 4-6 weeks until undetectable 2

• Assess adherence and tolerability at each visit 2
• Once viral suppression is achieved, continue monitoring per standard guidelines (typically every 3-6 months)

Monitor CD4 count every 6 months until >250 cells/μL for at least 1 year with viral suppression 2

• Discontinue CD4 monitoring after CD4 >500 cells/μL for 2 years with sustained viral suppression 2

Children

• CD4 values in healthy infants are considerably higher than adults and decrease gradually to reach adult values by 6 years of age 5
• Infants with defective thymic profile (CD4 <1,900/mm³ and CD8 >850/mm³) during the first 6 months have more rapid disease progression 5

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Second-Line Therapy for Virologic Failure

While the provided evidence does not extensively detail second-line regimens, the principles are:

• Switch to a regimen with at least two (preferably three) fully active drugs based on resistance testing 1
• Use drugs from different classes than the failing regimen 1
• InSTIs with high resistance barriers (dolutegravir, bictegravir) are preferred in second-line regimens when not used in first-line 1
• Assess and address adherence barriers before changing regimens, as poor adherence is the most common cause of virologic failure 8

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Common Pitfalls and How to Avoid Them

1. Delaying ART for complete lab results: Start treatment immediately; only wait for HLA-B*5701 if planning abacavir use 1, 2, 3

2. Using abacavir or NNRTIs for same-day start: These require baseline testing; use tenofovir-based regimens instead 1, 3

3. Starting ART too early in cryptococcal meningitis: Wait 4-6 weeks after antifungal therapy to reduce IRIS risk 1, 3

4. Assuming rapid ART alone ensures long-term success: Implement robust care engagement strategies addressing housing, food, and cultural sensitivity, as rapid initiation may not sustain viral suppression beyond 12 months without comprehensive support 1, 4

5. Forgetting age-specific CD4 thresholds in children: Pediatric CD4 counts are much higher than adults; use age-appropriate cutoffs for prophylaxis decisions 5

6. Overlooking drug interactions in pregnancy: Use twice-daily darunavir/ritonavir dosing in pregnant patients, not once-daily 2

7. Initiating MAC prophylaxis with immediate ART: This is unnecessary and no longer recommended 1, 2, 3