The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial assessed the effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445 women) with placebo gel (n = 444 women) in sexually active, HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (person time of study observation) (38 out of 680.6 women-years) compared with 9.1 per 100 women-years (60 out of 660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence > 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence < 50%), the HIV incidence reduction was 38 and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.

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Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(04)17140-7.pdf

Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis

Objective  To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design  Systematic review and meta-analysis of cohort studies. Data sources  PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies  Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction  Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results  There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions  There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

https://www.bmj.com/content/bmj/353/bmj.i1753.full.pdf

Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

Associations: Most common: S. aureus Foreign body: Coagulase-negative Staphylococcus or P. acnes Nosocomial: Enterobacteraceae, P. aeruginosa, Candida Bites, diabetic foot lesions, and decubitus ulcers: Streptococci and anaerobes Sickle cell disease: Salmonella or S. pneumonia HIV: Bartonella Bites, human or animal: P. multocida, E. corrodens Immunosuppressed: Aspergillis, C. albicans, Mycobacteria Populations where these organisms are prevalent: Brucella, TB, Coxiella burnetti, endemic fungi Microbiology and histology. The preferred culture sources are blood cultures (which are usually positive only with hematogenous osteomyelitis) or bone biopsy. Cultures from sinus tracts are often misleading. Tissue specimens showing more than 5 neutrophils/HPF show a sensitivity of 43% to 84% in specificity of 93% to 97% (AbdulKarim FW. Mod Pathol. 1998;11:427).

Recommendations for use of antiretroviral drugs in pregnant hiv-1-infected women for maternal health and interventions to reduce perinatal hiv-1 transmission in the United States

Background We analyzed individual patient data to determine the contribution of late postnatal transmission to the overall risk of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) and the timing and determinants of late postnatal transmission. Methods Eligible trials were conducted where breast-feeding was common; included >/=2 HIV-1 tests by 3 months, and, if follow-up continued, >/=2 tests at 3-12 months; and regularly assessed infant-feeding modality. Data on children born before January 2000 were analyzed. Results Of 4085 children from 9 trials (breast-fed singletons for whom HIV-1 testing was performed), 993 (24%) were definitively infected (placebo arms, 25.9%; treatment arms, 23.4%; P=.08). Of 539 children with known timing of infection, 225 (42%) had late postnatal transmission. Late postnatal transmission occurred throughout breast-feeding. The estimated hazard function for time to late postnatal transmission was roughly constant. The cumulative probability of late postnatal transmission at 18 months was 9.3%. The overall risk of late postnatal transmission was 8.9 transmissions/100 child-years of breast-feeding and was significantly higher with lower maternal CD4(+) cell counts and male sex. Conclusions Late postnatal transmission contributes substantially to overall mother-to-child transmission of HIV-1. The risk of late postnatal transmission is generally constant throughout breast-feeding, and late postnatal transmission is associated with a lower maternal CD4(+) cell count and male sex. Biological and cultural mechanisms underlying the association between sex and late postnatal transmission should be further investigated. Interventions to decrease transmission of HIV-1 through breast-feeding are urgently needed.

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Late Postnatal Transmission of HIV-1 in Breast-Fed Children: An Individual Patient Data Meta-Analysis

Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial

Providing antiretroviral therapy to human immunodeficiency virus type 1 (HIV-1)-infected women at the onset of labor could offer a relatively simple and affordable means of preventing vertical transmission. The HIVNET 012 study team reported, in 1999, that a single-dose intrapartum/neonatal regimen of nevirapine significantly lowered the risk of mother-child transmission by 47% compared with a brief regimen of zidovudine. The 496 infants had been followed up for 14 to 16 weeks. Data now are available for these infants up to age 18 months. Participating mothers had been assigned to receive either 200 mg nevirapine at the onset of labor, with 2 mg/kg for the infant within 72 hours after birth (regimen A), or 600 mg zidovudine at the onset of labor, followed by 300 mg every 3 hours until delivery and then 4 mg/kg orally twice a day for 7 days for the infant (regimen B). Testing for HIV-1 estimated HIV-1 RNA up to age 1 year and HIV-1 antibody at age 18 months. The estimated risk of HIV-1 transmission was 10.3% with zidovudine and 8.1% in the nevirapine group at birth; 20% and 11.8%, respectively, by age 6 to 8 weeks; 22.1% and 13.5% by age 14 to 16 weeks; and 25.8% and 15.7% by age 18 months. In all, nevirapine was associated with a 41% reduction in the relative risk of HIV-1 transmission at last follow up (95% confidence interval, 16-59%). Multivariate analysis showed that highly significant factors, besides the treatment effect, included the baseline maternal viral load and CD4 cell count. Adjusting for breastfeeding status did not alter the treatment effect. Serious adverse infant events in the first 2 months after birth occurred in approximately 10% of both treatment groups, and events also were comparably frequent at age 18 months. Intrapartum/neonatal nevirapine appears to be a simple, inexpensive, and well-tolerated regimen for significantly reducing perinatal transmission of HIV-1 in less developed countries.

Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow up of the HIVNET 012 randomized trial

Corey Duefield

Papers

Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial

Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow up of the HIVNET 012 randomized trial