Updated October 2025

HIV Care Playbook

HIV Infection: Initial Evaluation and Antiretroviral Therapy

Immediate, comprehensive baseline evaluation paired with same-day initiation of a guideline-concordant INSTI-based regimen optimizes outcomes. Monitor virologic suppression and safety closely, address comorbidities and coinfections, and provide prevention and partner services.

Clinical question

What are the key elements of the initial evaluation for adults with newly diagnosed HIV and how should antiretroviral therapy (ART) be selected and initiated?

HIVARTIntegrase inhibitorsInitial evaluationOpportunistic infectionsPreventionGuidelines

Key points

Confirm Diagnosis and Stage

Confirm HIV with approved algorithm, obtain baseline CD4 count and HIV-1 RNA, and rapidly stage disease to guide OI prophylaxis and urgency of ART ^[1], ^[2].

Start ART Immediately

Initiate an INSTI-based regimen on the same day as diagnosis when feasible; adjust after baseline labs/genotype return ^[1], ^[2].

Prevent Infections

Screen for HBV/HCV, syphilis and STIs; provide OI prophylaxis by CD4 thresholds; vaccinate per HIV schedules ^[1], ^[3], ^[2].

Monitor and Optimize

Check HIV RNA at 2–4 weeks and every 4–8 weeks until suppressed; monitor safety labs and drug–drug interactions; address adherence and barriers ^[1], ^[2].

Partner Services and Prevention

Offer partner notification, PrEP/PEP for partners, and risk-reduction counseling per public health guidance ^[3], ^[2].

Evidence highlights

Start same day when possible ^[1], ^[2]

ART Start

HIV-1 RNA <200 copies/mL by 3–6 months ^[1]

Primary Goal

U=U when RNA <200 copies/mL ^[2]

Public Health

Initial Workup

Baseline Evaluation and Rapid ART

A structured intake captures disease stage, comorbidities, transmission risk, and immediate treatment needs while enabling rapid ART initiation.

Confirm HIV and Assess Stage

Confirm diagnosis per standard algorithm; obtain CD4 cell count and plasma HIV-1 RNA to determine immune status and urgency of OI prophylaxis. Perform focused history, physical exam, TB symptom screen, pregnancy status, mental health, substance use, and social determinants affecting adherence ^[1], ^[2].

Baseline Laboratories

Order: HIV-1 RNA, CD4, CBC, CMP (including AST/ALT, creatinine), urinalysis if TDF use considered, HLA-B*57:01 if abacavir possible, fasting lipids/glucose or A1c, pregnancy test, HAV/HBV serologies (HBsAg, anti-HBs, anti-HBc), anti-HCV Ab with RNA reflex, syphilis, GC/CT NAATs by exposure sites, toxoplasma IgG (if indicated), TB testing (IGRA/PPD), G6PD (if dapsone possible). Obtain baseline resistance genotype (RT, PR; add integrase if prior exposure risk) before or at ART start; do not delay ART pending results unless concerns for transmitted INSTI resistance or cryptococcal/TB meningitis ^[1], ^[2].

Immediate Prevention and Public Health

Provide counseling on condom use and risk reduction; offer partner notification and linkage to public health services; discuss U=U once viral load is durably suppressed. For recent exposures in partners (<72 hours), offer PEP; offer PrEP to HIV-negative partners ^[3], ^[2].

Initiate ART Same Day

Begin a recommended INSTI-based regimen at diagnosis when possible. Modify when genotype/serologies return (e.g., HBV coinfection requires dual HBV-active agents). Defer only in select CNS OIs where short delay may be indicated (e.g., cryptococcal meningitis) ^[1], ^[2].

Regimens and Follow-up

First-Line ART, Special Situations, and Monitoring

Preferred initial regimens emphasize high potency, high barrier to resistance, and favorable tolerability profiles.

Preferred Initial Regimens (Adults)

Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC): once daily; high barrier; active vs HBV with TAF/FTC ^[2].

Dolutegravir + tenofovir (TAF or TDF) + emtricitabine or lamivudine (DTG + TAF/TDF + FTC/3TC) ^[2].

Dolutegravir/lamivudine (DTG/3TC): use if HIV RNA <500,000 copies/mL, no HBV coinfection, and genotype/HBV results known; avoid if baseline resistance or unknown HBV status ^[2].

When to Avoid or Modify

HBV coinfection: ensure two HBV-active drugs (e.g., TAF or TDF + FTC/3TC); avoid 3TC or FTC alone without tenofovir ^[2].

Pregnancy or planning: use guideline-supported regimens with established safety; confirm drug–drug interactions ^[2].

Severe renal disease: prefer TAF over TDF or use non–tenofovir backbones as indicated ^[2].

Active opportunistic CNS infections (e.g., cryptococcal meningitis): consider short delay in ART initiation per OI-specific guidance ^[1], ^[2].

Monitoring After ART Start

HIV-1 RNA at 2–4 weeks after initiation, then every 4–8 weeks until <200 copies/mL; once suppressed, every 3–6 months ^[1], ^[2].

CD4 count every 3–6 months until >200–300 cells/µL and stable; then less frequently ^[1], ^[2].

Safety: CBC, CMP at baseline and 2–8 weeks post-start, then per regimen; monitor renal function (TDF) and lipids (TAF/boosted regimens) ^[1], ^[2].

Adherence/support: assess at each visit; address side effects, access, mental health, housing, and substance use barriers ^[1], ^[2].

Opportunistic Infection Prophylaxis

Pneumocystis jirovecii: if CD4 <200 cells/µL, start TMP-SMX; discontinue once CD4 >200 for ≥3 months on ART ^[1].

Toxoplasma gondii: if CD4 <100 and toxo IgG+, TMP-SMX DS daily ^[1].

Mycobacterium avium complex: if CD4 <50 and not promptly starting ART, azithromycin weekly; stop when CD4 >100 for ≥3 months ^[1].

TB: screen all; treat latent TB infection if indicated; coordinate timing with ART in active TB ^[1], ^[2].

Vaccination and Health Maintenance

Administer inactivated vaccines per schedule: influenza annually, COVID-19, PCV followed by PPSV23 as indicated, Tdap, HPV (through age thresholds), hepatitis A/B if nonimmune ^[1], ^[2].

Avoid live vaccines when CD4 is low; consider when immune reconstitution achieved per guidelines ^[1], ^[2].

Screen for cervical cancer; age- and sex-appropriate cancer screening; cardiovascular risk management given ART-associated and HIV-related risks ^[4], ^[1].

If Virologic Failure or Incomplete Response

Confirm adherence, interactions, and proper dosing first; repeat HIV RNA in 2–4 weeks ^[1].

Obtain resistance testing while on failing regimen or within 4 weeks of discontinuation ^[1].

Construct a new regimen with ≥2, preferably ≥3 fully active agents, prioritizing high-barrier drugs (e.g., DTG, BIC, boosted DRV) ^[2].

Evidence Signals

Efficacy, Long-Term Outcomes, and Special Populations

Potent ART achieves high suppression and improves survival; attention to aging, comorbidities, and regimen safety is essential.

Therapeutic Success with Contemporary ART

Modern regimens achieve high therapeutic success at 48 weeks, with reports of ~84% success and no virologic failures in selected cohorts, alongside high treatment satisfaction, indicating robust short-term efficacy and tolerability ^[5].

Benefits of Early ART

Early initiation reduces transmission and improves clinical outcomes, reinforcing the public health and individual benefits of same-day ART; consolidated global guidance endorses rapid start and streamlined monitoring ^[2].

Aging with HIV

Older adults often have slower CD4 recovery but equal or better virologic suppression, necessitating vigilance for comorbidity management and drug interactions while maintaining potent ART ^[6].

Cardiometabolic Considerations

HIV and certain ART exposures have been linked with increased cardiovascular risk; integrated risk assessment and modification are recommended during routine care ^[4].

References

Source material

Primary literature that informs this article.