Residency · Residency · Medicine Pediatrics

HIV Across the Lifespan

Overview

HIV infection remains a global health challenge with ~39 million people living with HIV worldwide. Pediatric HIV is primarily acquired perinatally; adult HIV through sexual transmission and injection drug use. Antiretroviral therapy (ART) has transformed HIV into a chronic manageable disease with near-normal life expectancy when treated early. Med-Peds physicians manage perinatally infected children transitioning to adult care, adolescent prevention (PrEP), and lifelong ART management.

Perinatal Transmission Prevention

Mother-to-Child Transmission (MTCT)

Without intervention: 15-45% transmission risk (antepartum, intrapartum, breastfeeding) With optimal ART, elective C-section when indicated, and formula feeding: <1% transmission. Key interventions: Universal prenatal HIV screening (opt-out testing at first prenatal visit and repeat in third trimester in high-prevalence areas) ART for all pregnant women with HIV regardless of CD4 count or viral load. Goal: undetectable viral load (<50 copies/mL) by delivery. Zidovudine (AZT) IV during labor if viral load >1000 near delivery. Scheduled C-section at 38 weeks if viral load >1000 at 36 weeks. Neonatal ART prophylaxis: AZT for 4 weeks (low risk) or enhanced prophylaxis with AZT + lamivudine + nevirapine/raltegravir for 6 weeks (high risk)

Breastfeeding Considerations

In resource-rich settings: formula feeding recommended to eliminate breastfeeding transmission risk. In resource-limited settings: WHO recommends breastfeeding with maternal ART (benefits of breastfeeding outweigh risk of HIV transmission when mother is virally suppressed) US guidelines now include shared decision-making for women on suppressive ART who desire to breastfeed.

Pediatric HIV Diagnosis

Virologic Testing (Infants <18 months)

HIV antibody tests are unreliable in infants (maternal antibodies persist up to 18 months) Use HIV DNA PCR or HIV RNA (viral load) for diagnosis. Testing schedule: birth (or within 48 hours), 14-21 days, 1-2 months, 4-6 months. Presumptive exclusion: 2 negative virologic tests (one at >= 1 month and one at >= 4 months) Definitive exclusion: 2 negative tests at >= 1 month and >= 4 months, OR negative HIV antibody at >= 18 months, if no breastfeeding.

Serologic Testing (Children >= 18 months and Adults)

Fourth-generation Ag/Ab combination test (detects both p24 antigen and HIV-1/2 antibodies): preferred initial screen. If reactive: HIV-1/HIV-2 differentiation assay. If indeterminate: HIV RNA (NAT) to detect acute infection. Window period: 4th-gen test detects ~99% by 6 weeks post-exposure.

<image>HIV diagnostic algorithm comparing virologic testing approach for infants under 18 months versus serologic testing for older children and adults with key decision points and confirmatory steps</image>

Antiretroviral Therapy

Pediatric ART

Treat ALL children with HIV regardless of age, CD4 count, or symptoms (WHO and US DHHS guidelines) Urgency: immediate treatment for infants <1 year (rapid disease progression without treatment). HLA-B*5701 testing before abacavir (hypersensitivity risk) Liquid formulations essential for young children; palatability affects adherence. Growth, development, and puberty monitoring are critical.

Adult ART

Treat ALL adults with HIV regardless of CD4 count — rapid initiation (same-day start) improves outcomes. Preferred initial regimens: Bictegravir/emtricitabine/TAF (Biktarvy): single-tablet regimen, high barrier to resistance. Dolutegravir + emtricitabine/TAF (or TDF): alternative INSTI-based regimen. Dolutegravir/lamivudine (Dovato): 2-drug regimen, acceptable if HBV negative and viral load <500,000. INSTI-based regimens (dolutegravir, bictegravir) are preferred over NNRTI and PI-based regimens due to higher efficacy, higher barrier to resistance, and fewer side effects. Considerations: renal function (TAF preferred over TDF if eGFR concerns), bone density, drug interactions, pregnancy planning.

Long-Acting Injectable ART

Cabotegravir + rilpivirine (Cabenuva): IM injections every 1-2 months; non-inferior to daily oral ART. Indications: patients who prefer injections over pills, adherence challenges, pill fatigue. Requires initial oral lead-in or can initiate directly with injections. Not yet approved for pediatric use; adolescent studies ongoing. Lenacapavir: every 6-month subcutaneous injection; approved for multidrug-resistant HIV.

Monitoring on ART

HIV viral load: at baseline, 2-4 weeks after starting/changing ART, then every 3-6 months; goal: undetectable (<50 copies/mL) CD4 count: at baseline, every 3-6 months initially; can monitor less frequently once stable and immune reconstitution achieved. Metabolic monitoring: fasting lipids, glucose, renal function, hepatic function. HBV coinfection: test before ART initiation; TAF or TDF in the regimen provides dual activity. Drug resistance testing: at diagnosis (before ART) and at virologic failure.

Opportunistic Infection Prophylaxis

Pneumocystis jirovecii Pneumonia (PCP)

Pediatric: TMP-SMX prophylaxis for all HIV-exposed infants starting at 4-6 weeks until HIV infection excluded; for HIV-infected children based on age-specific CD4 thresholds. Adult: TMP-SMX when CD4 <200 or CD4% <14% or history of oropharyngeal candidiasis. Can discontinue when CD4 >200 for >= 3 months on ART.

Mycobacterium avium Complex (MAC)

Primary prophylaxis (azithromycin): when CD4 <50 (adults) or age-specific thresholds in children. Can discontinue when CD4 recovered on ART.

Toxoplasmosis

TMP-SMX (same dose as PCP prophylaxis) provides coverage when CD4 <100 and positive Toxoplasma IgG.

<image>Table of opportunistic infection prophylaxis thresholds comparing CD4 count triggers in children by age group versus adults for PCP, MAC, and toxoplasmosis with preferred prophylactic agents</image>

HIV Prevention

Pre-Exposure Prophylaxis (PrEP)

Oral PrEP: emtricitabine/TDF (Truvada) or emtricitabine/TAF (Descovy — not for receptive vaginal sex); daily dosing; reduces HIV acquisition by >99% with adherence. Injectable PrEP: cabotegravir (Apretude) IM every 2 months; superior to oral TDF/FTC in clinical trials. Indications: sexually active adults and adolescents at substantial risk (MSM, transgender women, serodiscordant couples, persons with recent STI, sex workers, IVDU) Adolescent considerations: PrEP approved for adolescents >= 35 kg; confidentiality and access without parental consent varies by jurisdiction. Monitoring: HIV testing before initiation and every 3 months; renal function; STI screening.

Post-Exposure Prophylaxis (PEP)

Initiate within 72 hours of exposure (sooner is better; ideally within 2 hours) 28-day course of 3-drug ART: preferred regimen — TDF/FTC + raltegravir or dolutegravir. Indications: occupational (needlestick) and non-occupational (sexual assault, condom failure) Follow-up: HIV testing at baseline, 4-6 weeks, and 3 months post-exposure.

Undetectable = Untransmittable (U=U)

Individuals with sustained undetectable viral load (<200 copies/mL) on ART effectively have zero risk of sexual HIV transmission. PARTNER 1 & 2 studies and HPTN 052: zero linked transmissions in serodiscordant couples. Cornerstone of HIV prevention messaging and destigmatization.

Transition of Care: Pediatric to Adult HIV

Challenges

Perinatally infected youth reaching adulthood face unique challenges: lifelong ART, resistance mutations from early (less effective) regimens, psychological burden of living with HIV since birth. Loss to follow-up during transition is a major risk — mortality spike in 18-25 age group. Neurocognitive effects of HIV and ART on the developing brain. Mental health comorbidities: depression, anxiety, PTSD, substance use. Disclosure challenges: when and how to disclose HIV status to adolescents (typically ages 8-12, developmentally appropriate)

Transition Framework

Use Got Transition or similar structured approach. Begin transition planning at age 12-14. Assess readiness: medication self-management, understanding of disease, appointment attendance. Joint visits with pediatric and adult providers during transition period. Warm handoff: ideally a clinic visit with both teams present. Maintain support: peer navigators, case managers, social workers.

Complications and Comorbidities

Non-AIDS-Defining Comorbidities (Chronic HIV)

Cardiovascular disease: increased risk even with suppressive ART; manage traditional risk factors aggressively. Metabolic syndrome: dyslipidemia (especially older PIs), insulin resistance. Osteoporosis: accelerated bone loss; DEXA screening at age 50 (or earlier if risk factors) Renal disease: HIV-associated nephropathy (HIVAN), TDF-associated tubulopathy. Neurocognitive disorders: HIV-associated neurocognitive disorder (HAND); screen regularly. Malignancies: increased risk of non-AIDS-defining cancers (lung, liver, anal); age-appropriate cancer screening + anal pap in MSM and women with cervical dysplasia.

AIDS-Defining Illnesses

PCP pneumonia, cerebral toxoplasmosis, cryptococcal meningitis, CMV retinitis, disseminated MAC, Kaposi sarcoma, primary CNS lymphoma, progressive multifocal leukoencephalopathy. Immune reconstitution inflammatory syndrome (IRIS): paradoxical worsening of opportunistic infection after ART initiation; more common with low CD4 at ART start.

<image>Timeline diagram showing the natural history of untreated HIV infection from acute seroconversion through clinical latency to AIDS, with CD4 count and viral load curves, and overlay of when opportunistic infections typically occur at different CD4 thresholds</image>

Clinical Pearls

All pregnant women must be tested for HIV — perinatal transmission is nearly 100% preventable with appropriate interventions. Acute HIV (acute retroviral syndrome) presents like mononucleosis: fever, pharyngitis, lymphadenopathy, rash, myalgias; standard antibody tests may be negative — order 4th-gen Ag/Ab or HIV RNA. CD4 count normal ranges are higher in children than adults — age-specific thresholds must be used for staging and prophylaxis decisions. Dolutegravir is now the backbone of most regimens across ages due to high barrier to resistance, efficacy, and tolerability; weight gain is an emerging concern. U=U is one of the most important messages in modern HIV care — reduces stigma and empowers patients. In adolescents, PrEP should be offered proactively — they are the fastest-growing demographic for new HIV infections in many regions. Drug-drug interactions are critical: rifampin significantly reduces PI and NNRTI levels; cobicistat and ritonavir (boosters) have extensive interaction profiles; always check interactions before prescribing.

References

• Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. DHHS. Updated 2024.
• Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. DHHS. Updated 2024.
• Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission. DHHS. Updated 2024.
• Rodger AJ, Cambiano V, Bruun T, et al. Risk of HIV Transmission Through Condomless Sex in Serodifferent Gay Couples with the HIV-Positive Partner Taking Suppressive ART (PARTNER): Final Results of a Multicentre Prospective Observational Study. Lancet. 2019;393(10189):2428-2438.

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