Analysis of HIV tropism in Ugandan infants.

HIV-infected infants may have CXCR4-using (X4-tropic) HIV, CCR5-using (R5-tropic) HIV, or a mixture of R5-tropic and X4-tropic HIV (dual/mixed, DM HIV). The level of infectivity for R5 virus (R5-RLU) varies among HIV infected infants. HIV tropism and R5-RLU were measured in samples from HIV-infected Ugandan infants using a commercial assay. DM HIV was detected in 7/72 (9.7%) infants at the time of HIV diagnosis (birth or 6-8 weeks of age, 4/15 (26.7%) with subtype D, 3/57 (5.3 %) with other subtypes, P=0.013). A transition from R5-tropic to DM HIV was observed in only two (6.7%) of 30 infants over 6-12 months. Six (85.7%) of seven infants with DM HIV died, compared to 21/67 (31.3%) infants with R5-tropic HIV (p=0.09). Higher R5-RLU at 6-8 weeks was not associated with decreased survival. Infants with in utero infection had a higher median R5-RLU than infants who were HIV-uninfected at birth (p=0.025).

In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine.

Use of single dose nevirapine (sdNVP) to prevent HIV mother-to-child transmission is associated with the emergence of NVP resistance in many infants who are HIV infected despite prophylaxis. We combined results from four clinical trials to analyze predictors of NVP resistance in sdNVP-exposed Ugandan infants. Samples were tested with the ViroSeq HIV Genotyping System and a sensitive point mutation assay (LigAmp, for detection of K103N, Y181C, and G190A). NVP resistance was detected at 6-8 weeks in 36 (45.0%) of 80 infants using ViroSeq and 33 (45.8%) of 72 infants using LigAmp. NVP resistance was more frequent among infants who were infected in utero than among infants who were diagnosed with HIV infection after birth by 6-8 weeks of age. Detection of NVP resistance at 6-8 weeks was not associated with HIV subtype (A vs. D), pre-NVP maternal viral load or CD4 cell count, infant viral load at 6-8 weeks, or infant sex. NVP resistance was still detected in some infants 6-12 months after sdNVP exposure. In this study, in utero HIV infection was the only factor associated with detection of NVP resistance in infants 6-8 weeks after sdNVP exposure.

Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission.

Single-dose (SD) nevirapine (NVP) significantly reduces mother-to-child transmission of human immunodeficiency virus (HIV). We analyzed NVP resistance after receipt of SD NVP in 57 previously SD NVP-naive women, in 34 SD NVP-experienced women, and in 17 HIV-infected infants. The proportion of women infected with variants with resistance mutations, the types of mutations detected, and the frequency and level of K103N were similar in the two groups of women at 6 weeks and 6 months post partum. NVP resistance was detected in a similar proportion of infants born to SD NVP-naive versus SD NVP-experienced women. Repeated use of SD NVP to prevent HIV transmission does not appear to influence NVP resistance.

Effectiveness of repeat single-dose nevirapine for prevention of mother-to-child transmission of HIV-1 in repeat pregnancies in Uganda.

BACKGROUND: Single-dose nevirapine (SDNVP) is widely used to prevent mother-to-child HIV transmission in resource-limited settings. Given detection of resistant mutants among women who receive SDNVP, concerns have arisen over the efficacy of SDNVP in repeat pregnancies. METHODS: Retrospective data were collected from SDNVP-exposed and -unexposed women from the HIV Network for Prevention 012 trial who subsequently received SDNVP in another pregnancy. Prospective data were collected from pregnant women who were SDNVP exposed or unexposed before delivery. Kaplan-Meier and Cox regression analyses were used to estimate rates of HIV infection and HIV-free survival among infants born to women with or without prior SDNVP exposure. RESULTS: In the retrospective cohort, the infection rates were 11.3% and 16.7% for 104 infants of NVP-exposed and -unexposed mothers, respectively (P = 0.41). In the prospective cohort, among 103 infants of NVP-exposed and -unexposed mothers, the 12-month infant HIV infection rates were 20.5% and 18.7% (P = 0.81) and HIV-free survival rates were 74.4% and 78.1% (P = 0.66), respectively. CONCLUSIONS: There was no increased risk of infant HIV infection among SDNVP-exposed women compared with -unexposed women. These findings support current international guidelines to offer SDNVP to HIV-infected pregnant women, regardless of previous SDNVP exposure, when more complex prophylaxis regimens are not available.

Risk of adverse pregnancy outcomes in young adolescent parturients in an inner-city hospital.

OBJECTIVE: Our purpose was to determine the relationship between adolescence and pregnancy-related outcomes. STUDY DESIGN: A retrospective cohort study was conducted in a population of adolescents delivered in a large inner-city hospital. The study population consisted of 14,718 adolescents and 11,830 nonadolescent controls. Pregnancy outcomes were compared in young adolescents (n = 2930) and mature adolescents (n = 11,788) versus controls. RESULTS: Adolescents were significantly more likely than controls to be African American, single, diagnosed with a sexually transmitted disease during pregnancy, and reside with others (P <.001). Adolescents were significantly more likely than controls to have eclampsia (relative risk [RR] 2.23, 95% CI 1.37-3.66) and preterm delivery (RR 1.12, 95% CI 1.04-1.21). Young adolescents were significantly more likely than controls to have preeclampsia (RR 1.33, 95% CI 1.15-1.54), eclampsia (RR 3.24, 95% CI 1.70-6.14), preterm delivery (RR 1.47, 95% CI 1.31-1.64), low-birth-weight delivery (RR 1.47, 95% CI 1.31-1.64), and very-low-birth-weight delivery (RR 1.25, 95% CI 1.01-1.56). Finally, mature adolescents were significantly more likely than controls to have eclampsia (RR 1.99, 95% CI 1.19-3.34). CONCLUSION: Young adolescents are at increased risk for adverse pregnancy outcomes.