Background Rates of pregnancy and HIV infection are high among adolescents. However, their engagement in prevention of mother-to-child HIV transmission (PMTCT) services is poorly characterized. We compared engagement in the PMTCT cascade between adult and adolescent mothers in Kenya. Methods We conducted a nationally representative cross-sectional survey of mother–infant pairs attending 120 maternal child health clinics selected by probability proportionate to size sampling, with a secondary survey oversampling HIV-positive mothers in 30 clinics. Antenatal care (ANC) attendance, HIV testing, and antiretroviral (ARV) use were compared between adolescent (age ≤19 years) and adult mothers using χ2 tests and logistic regression. Results Among 2521 mothers, 278 (12.8%) were adolescents. Adolescents were less likely than adults to be employed (16.5% vs. 37.9%), married (66.1% vs. 88.3%), have intended pregnancy (40.5% vs. 58.6%), or have disclosed their HIV status (77.5% vs. 90.7%) (P < 0.01 for all). Adolescents were less likely than adults to attend ≥4 ANC visits (35.2% vs. 45.6%, P = 0.002). This effect remained significant when adjusting for employment, household crowding, pregnancy intention, gravidity, and HIV status [adjusted odds ratio (95% confidence interval) = 0.54 (0.37 to 0.97), P = 0.001]. Among 2359 women without previous HIV testing, 96.1% received testing during pregnancy; testing levels did not differ between adolescents and adults. Among 288 HIV-positive women not on antiretroviral therapy before pregnancy, adolescents were less likely than adults to be on ARVs (65.0% vs. 85.8%, P = 0.01) or to have infants on ARVs (85.7% vs. 97.7%, P = 0.005). Conclusions Adolescent mothers had poorer ANC attendance and uptake of ARVs for PMTCT. Targeted interventions are needed to improve retention of this vulnerable population in the PMTCT cascade.

Late presentation is common among African HIV-1-infected infants. Incidence and correlates of mortality were examined in 99 infants with HIV-1 diagnosis by age 5 months. Twelve-month survival was 66.8% (95% confidence interval, 55.9%, 75.6%). WHO stage 3/4, underweight, wasting, microcephaly, low hemoglobin, pneumonia, and gastroenteritis predicted mortality. Early HIV-1 diagnosis with ART before symptomatic disease is critical for infant survival.

Background Resistance commonly arises in infants exposed to single-dose nevirapine (sdNVP) for prevention of mother to child transmission (PMTCT). While K103N and Y181C are common following sdNVP, multiple other mutations also confer NVP-resistance. It remains unclear whether specific NVP-resistance mutations or combinations of mutations predict virologic failure in infants when present at low frequencies prior to NVP-based treatment. Methods Twenty sdNVP-exposed infants who were subsequently treated with NVP-based highly active antiretroviral therapy (HAART) were examined. Pre-treatment plasma samples were tested for the presence of NVP-resistance mutations by allele-specific PCR (ASPCR) for K103N and Y181C and ultra-deep pyrosequencing (UDPS) for all primary NVP mutations. Viral levels were determined every 3 months for up to 24months on NVP-HAART. Cox proportional hazard models were used to determine correlates of viral failure. Results The NVP resistance mutations K103N or Y181C were detected in pre-treatment plasma samples in 6 infants by ASPCR. NVP resistance at these or other sites was detectable by UDPS in 10 out of 20 infants tested. Virologic failure occurred in 50% of infants with any NVP resistance mutations detected, while only 20% of infants without resistance experienced viral failure, but the difference was not significant (p=0.19). An increase in the number of NVP resistance mutations detectable by UDPS in an infant was significantly associated with an increased risk of virologic failure (HR=1.79 (95%CI: 1.07, 2.99), p=0.027). Conclusions Low frequencies of multiple NVP resistance mutations, in addition to K103N and Y181C, present in infants before NVP-based treatment may predict treatment outcome.

BackgroundDespite expanded programs for prevention of mother-to-child HIV transmission (PMTCT), HIV-infected infants may not be diagnosed until they are ill. Comparing HIV prevalence and outcomes in infants diagnosed in PMTCT programs to those in hospital settings may improve pediatric HIV diagnosis strategies.MethodsHIV-exposed infants <12 months old were recruited from 9 PMTCT sites in public maternal child health (MCH) clinics or from an inpatient setting in Nairobi, Kenya and tested for HIV using HIV DNA assays. A subset of HIV-infected infants <4.5 months of age was enrolled in a research study and followed for 2 years. HIV prevalence, number needed to test, infant age at testing, and turnaround time for tests were compared between PMTCT programs and hospital sites. Among the enrolled cohort, baseline characteristics, survival, and timing of antiretroviral therapy (ART) initiation were compared between infants diagnosed in PMTCT programs versus hospital.ResultsAmong 1,923 HIV-exposed infants, HIV prevalence was higher among infants tested in hospital than PMTCT early infant diagnosis (EID) sites (41% vs. 11%, p < 0.001); the number of HIV-exposed infants needed to test to diagnose one infection was 2.4 in the hospital vs. 9.1 in PMTCT. Receipt of HIV test results was faster among hospitalized infants (7 vs. 25 days, p < 0.001). Infants diagnosed in hospital were older at the time of testing than PMTCT diagnosed infants (5.0 vs. 1.6 months, respectively, p < 0.001).In the subset of 99 HIV-infected infants <4.5 months old followed longitudinally, hospital-diagnosed infants did not differ from PMTCT-diagnosed infants in time to ART initiation; however, hospital-diagnosed infants were >3 times as likely to die (HR = 3.1, 95% CI = 1.3-7.6).ConclusionsAmong HIV-exposed infants, hospital-based testing was more likely to detect an HIV-infected infant than PMTCT testing. Because young symptomatic infants diagnosed with HIV during hospitalization have very high mortality, every effort should be made to diagnose HIV infections before symptom onset. Systems to expedite turnaround time at PMTCT EID sites and to routinize inpatient pediatric HIV testing are necessary to improve pediatric HIV outcomes.

Objective Treatment interruption (TI) has been safe and durable in some pediatric studies but none have compared TI to continued antiretroviral treatment (ART) following ART initiation in early HIV. The objective of this study was to compare outcomes in TI versus continued ART among early-treated infants. Design Randomized trial (OPH-03; NCT00428116) Methods The trial included HIV-infected infants who initiated ART at <13 months of age, received ART for 24 months, and, if eligible (CD4>25%, normal growth), were randomized to TI vs. continued ART. Children in the TI group re-started ART if they met WHO ART-eligibility criteria. During 18-months post-randomization, primary outcomes were incidence of serious adverse events (SAEs) and growth. CD4, viral load, morbidity, and growth were compared. Results Of 140 infants enrolled, 121 started ART, of whom 75 completed ≥24 months ART and 42 were randomized (21 per arm). ART was initiated at median age 5 months and randomization at 30 months. Among 21 TI children, 14 met ART re-start criteria within 3 months. Randomization was discontinued by DSMB due to low TI durability. At 18 months post-randomization, growth and SAEs were comparable between arms; hypercholesteremia incidence was higher in the continued arm (p=0.03). CD4% and VL did not differ between arms (CD4% 35% and median VL undetectable (<150 c/ml) in both arms, p=0.9 for each comparison). No infants had post-treatment viral control. Conclusion Short TI did not compromise 18-month CD4%, viral control, growth, or morbidity compared to continued ART among infants who started ART in early HIV infection.