Maternal and infant antiretroviral regimens to prevent postnatal HIV-1 transmission: 48-week follow-up of the BAN randomised controlled trial.

BACKGROUND: In resource-limited settings where no safe alternative to breastfeeding exists, WHO recommends that antiretroviral prophylaxis be given to either HIV-infected mothers or infants throughout breastfeeding. We assessed the effect of 28 weeks of maternal or infant antiretroviral prophylaxis on postnatal HIV infection at 48 weeks. METHODS: The Breastfeeding, Antiretrovirals, and Nutrition (BAN) Study was undertaken in Lilongwe, Malawi, between April 21, 2004, and Jan 28, 2010. 2369 HIV-infected breastfeeding mothers with a CD4 count of 250 cells per µL or more and their newborn babies were randomly assigned with a variable-block design to one of three, 28-week regimens: maternal triple antiretroviral (n=849); daily infant nevirapine (n=852); or control (n=668). Patients and local clinical staff were not masked to treatment allocation, but other study investigators were. All mothers and infants received one dose of nevirapine (mother 200 mg; infant 2 mg/kg) and 7 days of zidovudine (mother 300 mg; infants 2 mg/kg) and lamivudine (mothers 150 mg; infants 4 mg/kg) twice a day. Mothers were advised to wean between 24 weeks and 28 weeks after birth. The primary endpoint was HIV infection by 48 weeks in infants who were not infected at 2 weeks and in all infants randomly assigned with censoring at loss to follow-up. This trial is registered with ClinicalTrials.gov, number NCT00164736. FINDINGS: 676 mother-infant pairs completed follow-up to 48 weeks or reached an endpoint in the maternal-antiretroviral group, 680 in the infant-nevirapine group, and 542 in the control group. By 32 weeks post partum, 96% of women in the intervention groups and 88% of those in the control group reported no breastfeeding since their 28-week visit. 30 infants in the maternal-antiretroviral group, 25 in the infant-nevirapine group, and 38 in the control group became HIV infected between 2 weeks and 48 weeks of life; 28 (30%) infections occurred after 28 weeks (nine in maternal-antiretroviral, 13 in infant-nevirapine, and six in control groups). The cumulative risk of HIV-1 transmission by 48 weeks was significantly higher in the control group (7%, 95% CI 5-9) than in the maternal-antiretroviral (4%, 3-6; p=0·0273) or the infant-nevirapine (4%, 2-5; p=0·0027) groups. The rate of serious adverse events in infants was significantly higher during 29-48 weeks than during the intervention phase (1·1 [95% CI 1·0-1·2] vs 0·7 [0·7-0·8] per 100 person-weeks; p<0·0001), with increased risk of diarrhoea, malaria, growth faltering, tuberculosis, and death. Nine women died between 2 weeks and 48 weeks post partum (one in maternal-antiretroviral group, two in infant-nevirapine group, six in control group). INTERPRETATION: In resource-limited settings where no suitable alternative to breastfeeding is available, antiretroviral prophylaxis given to mothers or infants might decrease HIV transmission. Weaning at 6 months might increase infant morbidity. FUNDING: US Centers for Disease Control and Prevention.

Maternal or infant antiretroviral drugs to reduce HIV-1 transmission.

BACKGROUND: We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human immunodeficiency virus type 1 (HIV-1) in Malawi. METHODS: We randomly assigned 2369 HIV-1-positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen, infant nevirapine, or no extended postnatal antiretroviral regimen (control group). All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine. We used the Kaplan-Meier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1-negative 2 weeks after birth. Rates were compared with the use of the log-rank test. RESULTS: Among mother-infant pairs, 5.0% of infants were HIV-1-positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P=0.009) or the infant-regimen group (1.7%, P<0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P=0.02), and 2.6% in the infant-regimen group (P<0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction. CONCLUSIONS: The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials.gov number, NCT00164736.)

Out-of-pocket costs and HIV pre-exposure prophylaxis persistence in a US multicity demonstration project.

OBJECTIVE: To evaluate whether out-of-pocket (OOP) costs reduced HIV pre-exposure prophylaxis (PrEP) persistence. DATA SOURCE: Participants from five urban community health centers (CHCs) in four US cities enrolled in a PrEP demonstration project from September 2014 to August 2017. STUDY DESIGN: Patients initiating PrEP were followed quarterly until they withdrew from PrEP care or the study ended. Self-reported OOP medication and clinic visit costs were assessed by semiannual questionnaires. Persistence was defined as the time from study enrollment to the last visit after which two subsequent 3-month visits were missed. Multivariable Cox proportional hazard regression was used to assess the effect of demographics, insurance, and OOP costs on PrEP persistence. PRINCIPAL FINDINGS: Among 918 participants with OOP cost data, the average quarterly OOP cost was $34 (median: $5, IQR: $0-$25). Participants who were men, White, employed, completed college, and had commercial insurance had higher OOP costs. Higher OOP costs were not associated with lower PrEP persistence by Cox proportional hazards regression (adjusted hazard ratio = 1.00 per $50 increase, 95% CI = 0.97, 1.02). CONCLUSION: Among patients receiving care from these urban CHCs, OOP costs were low and did not undermine PrEP persistence.

Predictors of Perinatal HIV Transmission Among Women Without Prior Antiretroviral Therapy in a Resource-Limited Setting: The Breastfeeding, Antiretrovirals and Nutrition Study.

BACKGROUND: To investigate potential risk factors for perinatal (intrauterine and intrapartum) mother-to-child transmission (MTCT) of HIV in women unexposed to antiretroviral therapy (ART) during pregnancy. METHODS: We compared factors according to perinatal MTCT outcome among 2275 ART-naive (until the onset of labor) HIV-infected women in the Breastfeeding, Antiretrovirals and Nutrition study (2004-2010) in Lilongwe, Malawi. Factors included HIV viral load during pregnancy, food security, demographic characteristics, hematologic and blood chemistry measures, medical history and physical factors. Associations with perinatal MTCT and interactions with maternal viral load were assessed using simple and multivariable logistic regression. RESULTS: There were 119 (115 intrauterine and 4 intrapartum) cases of perinatal MTCT, only one to a mother with <1000 HIV copies/mL. Maternal viral loads >10,000 copies/mL were common (63.1%). Lower maternal viral load (<1000 copies/mL and 1000.1-10,000 copies/mL) was associated with reduced odds of perinatal MTCT [adjusted odds ratio (aOR), 0.1; 95% confidence interval (CI): 0.01-0.4 and aOR, 0.2; 95% CI: 0.1-0.4, respectively), compared with maternal viral load >10,000 copies/mL. Low CD4+ T cell count (≤350 cells/µL) was only associated with perinatal MTCT in unadjusted models. Food shortage (aOR, 1.8; 95% CI: 1.2-2.6), sexually transmitted infection (STI) (past year; aOR, 1.9; 95% CI: 1.0-3.7), histories of herpes zoster (aOR, 3.0; 95% CI: 1.6-5.6) and tuberculosis (aOR, 2.5; 95% CI: 1.1-5.7) were associated with increased odds of perinatal MTCT. CONCLUSIONS: These findings confirm that lowering maternal HIV viral load is most important in preventing perinatal MTCT and support efforts to address food shortage, STI and tuberculosis prevention, while informing programs to improve ART coverage in pregnancy.

Effects of concurrent exposure to antiretrovirals and cotrimoxazole prophylaxis among HIV-exposed, uninfected infants.

BACKGROUND: Given the potential of cotrimoxazole preventive therapy (CPT) to prevent bacterial and malarial infections in HIV-exposed, uninfected (HEU) infants, it is important to evaluate the effects of its concurrent use with antiretroviral agents that have overlapping toxicity profiles. METHODS: We used data from the Breastfeeding, Antiretrovirals, and Nutrition study (2004-2010) to evaluate the association of CPT and antiretrovirals with hematologic measures (hemoglobin, neutrophil, and alanine aminotransferase levels) from 6 to 48 weeks of age in 2006 HEU infants in Lilongwe, Malawi. Hazards of severe outcomes (anemia, neutropenia, and elevated alanine aminotransferase), as defined by the National Institutes of Health, were compared using Cox regression models, according to time-varying CPT (implemented June 2006), antiretroviral treatment arm (maternal triple antiretroviral, infant nevirapine, or none during 6 months of breastfeeding), and their interaction. The effects of these treatments on hemoglobin, neutrophil, and alanine aminotransferase levels were assessed using linear mixed models. RESULTS: In Cox models, CPT was associated with an increase in severe neutropenia [hazard ratio 1.97 (1.01, 3.86)] and a decrease in severe anemia (hazard ratio 0.65 (0.48, 0.88)]. Interactions between CPT and antiretroviral treatment were not significant. By 36 weeks, there was a significant association of CPT with increased hemoglobin levels regardless of antiretroviral drug exposure. CONCLUSIONS: In addition to expected associations with increased hazard of severe neutropenia and decreased neutrophil count, CPT was associated with reduced hazard of severe anemia and higher infant blood hemoglobin. This provides further support for CPT use in HEU infants in malaria-endemic resource-limited settings where anemia is prevalent.

Factors Associated with Contraceptive Use Differ between Younger and Older African-American Female Adolescents.

STUDY OBJECTIVE: To examine differences in factors associated with contraceptive use between younger and older adolescent age groups, which has not previously been well described. DESIGN: Age group-specific analyses were performed on cross-sectional survey data to identify factors associated with any contraceptive use at last sex among younger (14- to 16-year-old) and older (17- to 19-year-old) sexually active African American female adolescents; interaction analyses were used to assess whether these associations differed by age. SETTING: Adolescent reproductive health clinic in Atlanta, Georgia. PARTICIPANTS: Sexually active African American female adolescents 14-19 years of age. INTERVENTIONS: No intervention tested; cross-sectional design. MAIN OUTCOME MEASURE: Self-reported contraceptive use during most recent vaginal sex with a male partner. RESULTS: The prevalence of contraceptive use at last sex was identical in both groups; however, factors associated with contraceptive use differed according to age. The only factor associated with contraceptive use in both age groups was involvement in decisions about sexual health in the most recent relationship. Associations between factors and contraceptive use significantly differed according to age. History of sexually transmitted infection, age difference with partner, discussion of condoms with partner, and concurrent partners were important factors among younger adolescents; worry about pregnancy and discussion of birth control with partner were important among older adolescents. CONCLUSION: Factors associated with contraceptive use at last sex differ according to adolescent age; this should be considered when designing counseling and interventions for teens, as well as research.