Comprehensive Evidence-Based Clinical Management
Human Immunodeficiency Virus (HIV) is a retrovirus that attacks the immune system, specifically CD4+ cells. Without treatment, it progresses to Acquired Immunodeficiency Syndrome (AIDS). With current antiretroviral therapy (ART), HIV has become a manageable chronic condition.
Undetectable = Untransmittable
People with HIV who maintain an undetectable viral load DO NOT transmit the virus sexually.
HIV infection without evidence of significant immunosuppression
Moderate immunosuppression. Increased risk of some infections
AIDS - High risk of opportunistic infections
Once a person is classified as Stage 3 (AIDS), they remain in that stage even if CD4 counts increase with treatment. CD4 counts may improve, but the historical classification remains.
Achieve undetectable viral load (<50 copies/mL)
Increase and maintain CD4 count
Avoid AIDS-defining illnesses
Maintain near-normal life expectancy
U=U: Undetectable = Untransmittable
Select regimens with best safety profile
*If acute infection or recent exposure suspected, order HIV-1 RNA
| Test | Window | Characteristics |
|---|---|---|
| Combined Ag/Ab (4th gen) | 18-45 days | Detects p24 antigen + antibodies. Preferred |
| Antibody only (3rd gen) | 23-90 days | Detects antibodies only. Longer window. |
| Rapid test (blood) | Variable | Results in minutes. Requires confirmation if positive. |
| Oral rapid test | ~90 days | Lower sensitivity. DO NOT use for PrEP. Requires confirmation. |
| HIV-1 RNA (Viral load) | 10-14 days | Detects acute infection. Do not use as sole initial screening. |
Acute retroviral syndrome: Fever, lymphadenopathy, pharyngitis, rash, myalgias, headache (2-4 weeks post-exposure). High viral load = High transmissibility. Antibody test may be negative. Order HIV-1 RNA if clinical suspicion.
Syphilis, gonorrhea, chlamydia, genital herpes
Common coinfection, same transmission routes
Screen for HIV in all TB cases
Indicator opportunistic infection
May indicate immunosuppression
>10% of body weight
After confirming HIV diagnosis, a comprehensive evaluation should be performed before initiating ART.
| Test | Purpose |
|---|---|
| CD4 Count | Staging, guide for OI prophylaxis |
| HIV Viral Load (RNA) | Baseline, response monitoring |
| Resistance Genotype | Guide ART selection (include tropism if considering MVC) |
| HLA-B*5701 | Before using abacavir (hypersensitivity) |
| Complete Blood Count | Anemia, thrombocytopenia |
| CMP + LFTs | Baseline renal and hepatic function |
| Lipid Panel | Cardiovascular risk |
| Fasting Glucose / HbA1c | Diabetes |
| Urinalysis | Proteinuria, renal function |
| Infection | Test | Notes |
|---|---|---|
| Hepatitis B | HBsAg, Anti-HBs, Anti-HBc | Vaccinate if susceptible |
| Hepatitis C | Anti-HCV, HCV RNA if positive | Treat if positive |
| Syphilis | RPR/VDRL ± confirmatory | High coinfection prevalence |
| Tuberculosis | TST or IGRA + Chest X-ray | Treat latent TB if positive |
| Toxoplasma | Toxoplasma IgG | Defines need for prophylaxis if CD4 <100 |
| CMV | CMV IgG | Identifies reactivation risk |
| Chlamydia/Gonorrhea | NAAT (urine, pharynx, rectum based on exposure) | Repeat if ongoing risk factors |
Complete series if Anti-HBs negative
2 doses if susceptible
PCV20 or PCV15 + PPSV23
Annual (inactivated, NOT live)
Primary series + boosters
Up to age 45 if not vaccinated
Live vaccines (varicella, MMR, yellow fever) are contraindicated if CD4 <200. Consider if CD4 ≥200 with viral suppression.
ART should be initiated as soon as possible after diagnosis, ideally the same day or within the first 7 days, even before having all baseline laboratory results (except genotype if high risk of transmitted resistance).
Recommended regimens are safe, effective, with high genetic barrier to resistance, well tolerated, and can be administered once daily.
| Regimen | Components | Notes |
|---|---|---|
| Biktarvy® | BIC/TAF/FTC | One tablet daily. Excellent profile. First line. |
| Dovato® | DTG/3TC | One tablet daily. 2-drug regimen. Requires HBV negative. |
| DTG + TAF/FTC | Dolutegravir + Descovy® | Two tablets daily. |
| DTG + TDF/FTC | Dolutegravir + Truvada® (generic) | Lower cost option. Monitor renal function. |
Cabenuva® (Cabotegravir + Rilpivirine IM): Monthly or every 2 months injection. Option for patients with viral suppression who prefer to avoid daily oral medication or have adherence challenges.
High barrier to resistance (BIC, DTG). Excellent tolerability.
*ABC requires HLA-B*5701 negative
*RPV: Requires VL <100,000 and CD4 >200. Low barrier to resistance.
Require booster (ritonavir or cobicistat). High barrier to resistance.
Reserved for multidrug-resistant HIV.
First cause of failure. Identify barriers: side effects, missed doses, stigma, access issues.
Medications, supplements, antacids that may reduce ART levels.
While patient is on current regimen. Requires VL >500-1000 copies/mL.
Include at least 2 (ideally 3) active drugs. Expert consultation if extensive resistance.
Primary prophylaxis prevents the first episode of opportunistic infections in patients with severe immunosuppression.
| Infection | Indication (CD4) | Preferred Prophylaxis | Discontinue if |
|---|---|---|---|
| Pneumocystis jirovecii (PCP) | <200 cells/mm³ or oropharyngeal candidiasis or <14% CD4 |
TMP-SMX DS 1 tab/day or TMP-SMX SS 1 tab/day |
CD4 >200 for ≥3 months on ART |
| Toxoplasma gondii | <100 cells/mm³ + Toxoplasma IgG positive |
TMP-SMX DS 1 tab/day (same dose as PCP) |
CD4 >200 for ≥3 months on ART |
| MAC (M. avium complex) | <50 cells/mm³ | Azithromycin 1200 mg/week or 600 mg 2x/week |
NOT recommended if starting ART (ART is sufficient) |
| Latent Tuberculosis | TST ≥5mm or IGRA positive (any CD4) |
Isoniazid 300 mg + B6 x 9 months or Rifapentine/INH x 3 months |
Complete treatment |
| Histoplasmosis (endemic areas) |
<150 cells/mm³ | Itraconazole 200 mg/day | CD4 >150 for ≥6 months |
| Coccidioidomycosis (endemic areas) |
<250 cells/mm³ | Fluconazole 400 mg/day | CD4 >250 for ≥6 months |
TMP-SMX DS (160/800 mg) once daily provides simultaneous prophylaxis against PCP, toxoplasmosis, and some bacterial infections. It is the first-line agent for prophylaxis.
| Infection | Alternatives |
|---|---|
| PCP |
• Dapsone 100 mg/day (check G6PD) • Atovaquone 1500 mg/day with food • Pentamidine aerosol 300 mg/month |
| Toxoplasmosis |
• Dapsone 50 mg/day + Pyrimethamine 50 mg/week + Leucovorin 25 mg/week • Atovaquone 1500 mg/day ± Pyrimethamine + Leucovorin |
In patients with mild to moderate allergy, gradual desensitization can be attempted, as TMP-SMX is far superior to alternatives. Contraindicated in severe reactions (Stevens-Johnson, anaphylaxis).
Dry cough, progressive dyspnea, fever, elevated LDH
Ring-enhancing lesions, focal deficits, seizures
Headache, fever, subtle meningismus
Vision loss, floaters, "pizza pie" fundoscopy
Very common in HIV, atypical presentation
Violaceous lesions on skin, mucosa, visceral
Associated with profound immunosuppression
Fever, weight loss, anemia, hepatosplenomegaly
PrEP is highly effective (>99%) for preventing HIV acquisition in at-risk individuals when taken as directed.
| Medication | Dose | Indications |
|---|---|---|
| TDF/FTC (Truvada®) | 1 tablet daily oral | All (MSM, heterosexuals, PWID). Also 2-1-1 off-label for MSM. |
| TAF/FTC (Descovy®) | 1 tablet daily oral | Sexual risk (except receptive vaginal sex in cisgender women) |
| Cabotegravir IM (Apretude®) | 600 mg IM every 2 months | All with sexual risk. Better adherence. |
| Lenacapavir SC (Sunlenca®) | 927 mg SC every 6 months | Approved 2025. Excellent efficacy in trials. New |
Confirm negative (<7 days before start)
CrCl >60 mL/min for TDF; >30 for TAF
HBsAg (TDF/FTC active against HBV)
Syphilis, gonorrhea, chlamydia
PEP should be started as soon as possible, ideally within the first 2 hours and no later than 72 hours after exposure. Efficacy decreases significantly after 72 hours.
| Regimen | Dose |
|---|---|
| Biktarvy® (BIC/TAF/FTC) Preferred | 1 tablet daily x 28 days |
| DTG + TDF/FTC | DTG 50 mg + TDF/FTC 1 tab daily x 28 days |
| RAL + TDF/FTC | RAL 400 mg BID + TDF/FTC daily x 28 days |
If the patient has ongoing risk, they can transition directly to PrEP upon completing 28 days of PEP without interruption, after confirming HIV negative status.
| Parameter | Frequency | Target/Notes |
|---|---|---|
| Viral Load (HIV RNA) |
• Baseline • 2-4 weeks post-initiation (optional) • 4 weeks after change • Every 3-4 months until suppression • Every 6 months if stable |
<200 at 24 weeks <50 optimal (undetectable) |
| CD4 Count |
• Baseline • Every 3-6 months x 2 years • Annual if stable and CD4 >300 |
Goal: >500 Optional if VL suppressed and CD4 >500 x 2 years |
| Renal Function |
• Baseline • 3-6 months post-initiation • Annual (or more frequent with TDF) |
Creatinine, eGFR, urinalysis |
| Hepatic Panel | Baseline and per regimen | More frequent with HBV/HCV coinfection |
| Lipid Panel | Baseline, 4-8 weeks post-initiation, then annual | Increased CV risk in HIV |
| Glucose/HbA1c | Baseline, then annual | Higher diabetes risk |
| STIs | Baseline, then per risk (every 3-12 months) | Syphilis, gonorrhea, chlamydia |
Undetectable. Optimal goal. U=U applies.
Virological suppression. Acceptable for most purposes.
Low-level viremia. Repeat in 4-8 weeks. Assess adherence.
Virological failure (if confirmed). Evaluate resistance.
Transient VL elevations (50-200 copies/mL) that return to undetectable without treatment change are common and generally DO NOT require intervention. If persistent or increasing, investigate adherence and resistance.
Evaluate ASCVD risk. Statins if indicated. HIV = additional risk factor.
DEXA in women ≥50 years and men ≥50 with risk factors.
Regular monitoring. Caution with TDF in CKD.
Depression, anxiety screening. Increased risk.
Annual cervical cytology, colonoscopy, mammography per guidelines.
Review interactions regularly. Aging with HIV.
With adequate ART and undetectable viral load, vertical transmission risk is <1%. Without treatment it can be 15-45%.
All newborns of mothers with HIV require ARV prophylaxis. Regimen depends on risk (low vs high) based on maternal viral load and other factors.
With ART effectiveness, many people with HIV are reaching advanced ages. They develop age-associated comorbidities at earlier ages ("accelerated aging").
1.5-2x higher risk. Aggressive risk factor management.
HAND (HIV-Associated Neurocognitive Disorders). Periodic screening.
Higher prevalence. DEXA based on risk factors.
HIV-associated nephropathy and medication toxicity.
Higher risk of AIDS-related and non-AIDS-related cancers.
Multiple interactions. Regular review.
This educational tool is intended solely for healthcare professionals as a clinical reference. It is not meant to replace clinical judgment, individualized patient evaluation, or institutional protocols. HIV management guidelines are frequently updated. Always consult the most recent guidelines (DHHS, WHO, local guidelines) and consider patient-specific factors when making clinical decisions.