Hormonal contraception and HIV-1 disease progression among postpartum Kenyan women.

Objective: To assess the immediate and longer-term effects of the use of hormonal contraception on the progression of HIV-1 disease in postpartum women.

Design: A prospective cohort study.

Methods: Information on contraceptive use, breastfeeding and intercurrent illnesses was obtained from HIV-infected postpartum Kenyan women monthly in the first year postpartum and quarterly in the second year.

Early response to highly active antiretroviral therapy in HIV-1-infected Kenyan children.

Objectives: To describe the early response to World Health Organization (WHO)-recommended nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line highly active antiretroviral therapy (HAART) in HIV-1-infected Kenyan children unexposed to nevirapine.

Design: Observational prospective cohort.

Methods: HIV-1 RNA level, CD4 lymphocyte count, weight for age z score, and height for age z score were measured before the initiation of HAART and every 3 to 6 months thereafter.

Cloning and characterization of functional subtype A HIV-1 envelope variants transmitted through breastfeeding.

Previous studies of HIV-1 variants transmitted from mother-to-infant have focused primarily on computational analyses of partial envelope gene sequences, rather than analyses of functional envelope variants. There are very few examples of well-characterized functional envelope clones from mother-infant pairs, especially from envelope variants representing the most prevalent subtypes worldwide. To address this, we amplified the envelope variants present in 4 mother-infant transmission pairs, all of whom were infected with subtype A and three of whom presumably transmitted HIV-1 during the breastfeeding period.

Breast milk alpha-defensins are associated with HIV type 1 RNA and CC chemokines in breast milk but not vertical HIV type 1 transmission.

Alpha-defensins are proteins exhibiting in vitro anti-HIV-1 activity that may protect against mother-to-child transmission of HIV-1 via breast milk. Correlates of alpha-defensins in breast milk and transmission risk were determined in a cohort of HIV-1-infected pregnant women in Nairobi followed for 12 months postpartum with their infants. Maternal blood was collected antenatally and at delivery for HIV-1 viral load and infant HIV-1 infection status was determined < 48 h after birth and at months 1, 3, 6, 9, and 12.

Herpes simplex virus type 2 and risk of intrapartum human immunodeficiency virus transmission.

Objective: To determine whether herpes simplex virus type 2 (HSV-2) infection was associated with risk of intrapartum human immunodeficiency virus type 1 (HIV-1) transmission and to define correlates of HSV-2 infection among HIV-1-seropositive pregnant women.

Methods: We performed a nested case control study within a perinatal cohort in Nairobi, Kenya. Herpes simplex virus type 2 serostatus and the presence of genital ulcers were ascertained at 32 weeks of gestation.

HIV-1 disease progression in breast-feeding and formula-feeding mothers: a prospective 2-year comparison of T cell subsets, HIV-1 RNA levels, and mortality.

Background: There is conflicting evidence regarding the effects of breast-feeding on maternal mortality from human immunodeficiency virus type 1 (HIV-1) infection, and little is known about the effects of breast-feeding on markers of HIV-1 disease progression.

Methods: HIV-1-seropositive women were enrolled during pregnancy and received short-course zidovudine. HIV-1 RNA levels and CD4 cell counts were determined at baseline and at months 1, 3, 6, 12, 18, and 24 postpartum and were compared between breast-feeding and formula-feeding mothers.

Domestic violence and prevention of mother-to-child transmission of HIV-1.

Objectives: To determine the prevalence of life-time domestic violence by the current partner before HIV-1 testing, its impact on the uptake of prevention of mother-to-child transmission (PMTCT) interventions and frequency after testing.

Design: A prospective cohort.

Methods: Antenatally, women and their partners were interviewed regarding physical, financial, and psychological abuse by the male partner before HIV-1 testing and 2 weeks after receiving results.

Pediatric HIV type 1 vaccine trial acceptability among mothers in Kenya.

Vaccination of infants against human immunodeficiency virus type 1 (HIV-1) may prevent mother-to-child HIV-1 transmission. Successful trials and immunization efforts will depend on the willingness of individuals to participate in pediatric vaccine research and acceptance of infant HIV-1 vaccines. In a cross-sectional study, pregnant women presenting to a Nairobi antenatal clinic for routine care were interviewed regarding their attitudes toward participation in research studies and HIV-1 vaccine acceptability for their infants.

High uptake of postpartum hormonal contraception among HIV-1-seropositive women in Kenya.

Objectives: The objectives of this study were to determine patterns of contraceptive utilization among sexually active HIV-1-seropositive women postpartum and to identify correlates of hormonal contraception uptake.

Goal: The goal of this study was to improve delivery of family planning services to HIV-1-infected women in resource-limited settings.

Study Design: HIV-1-infected pregnant women were followed prospectively in a perinatal HIV-1 transmission study.

Predictors of mortality in HIV-1 exposed uninfected post-neonatal infants at the Kenyatta National Hospital, Nairobi.

Objectives: To identify potential predictors of mortality, to determine mortality rate and to identify prevalent causes of death in a cohort of HIV-1 exposed uninfected infants.

Design: Prospective cohort study.

Setting: Kenyatta National Hospital, Nairobi, Kenya.

Neutralization escape variants of human immunodeficiency virus type 1 are transmitted from mother to infant.

Maternal passive immunity typically plays a critical role in protecting infants from new infections; however, the specific contribution of neutralizing antibodies in limiting mother-to-child transmission of human immunodeficiency virus type 1 is unclear. By examining cloned envelope variants from 12 transmission pairs, we found that vertically transmitted variants were more resistant to neutralization by maternal plasma than were maternal viral variants near the time of transmission. The vertically transmitted envelope variants were poorly neutralized by monoclonal antibodies b12 [corrected] 2G12, 2F5, and 4E10 individually or in combination.

High maternal HIV-1 viral load during pregnancy is associated with reduced placental transfer of measles IgG antibody.

Background: Studies among HIV-1-infected women have demonstrated reduced placental transfer of IgG antibodies against measles and other pathogens. As a result, infants born to women with HIV-1 infection may not acquire adequate passive immunity in utero and this could contribute to high infant morbidity and mortality in this vulnerable population.

Methods: To determine factors associated with decreased placental transfer of measles IgG, 55 HIV-1-infected pregnant women who were enrolled in a Nairobi perinatal HIV-1 transmission study were followed.

CC and CXC chemokines in breastmilk are associated with mother-to-child HIV-1 transmission.

Introduction: CC and CXC chemokines may play a role in mother-to-child HIV-1 transmission by blocking HIV-1 binding to chemokine receptors and impeding viral entry into cells.

Methods: To define correlates of breastmilk chemokines and associations with infant HIV-1 acquisition, chemokines in breastmilk and infant HIV-1 infection risk were assessed in an observational, longitudinal cohort study. We measured MIP-1alpha, MIP-1beta, RANTES, and SDF-1 in month 1 breastmilk specimens from HIV-1-infected women in Nairobi and HIV-1 viral load was calculated in maternal plasma and breastmilk at delivery and 1 month postpartum.

Breast milk HIV-1 suppression and decreased transmission: a randomized trial comparing HIVNET 012 nevirapine versus short-course zidovudine.

Objective: To compare the effect of perinatal regimens of short-course nevirapine (HIVNET 012) and zidovudine [Thai-Centers for Disease Control and Prevention (CDC) regimen] on breast milk viral shedding and perinatal transmission during the first 6 weeks postpartum in a randomized clinical trial.

Design: Randomized clinical trial.

Methods: Pregnant HIV-1 seropositive women in Nairobi, Kenya who planned to breastfeed were randomized to HIVNET 012 or Thai-CDC regimens.

Modified vaccinia Ankara expressing HIVA antigen stimulates HIV-1-specific CD8 T cells in ELISpot assays of HIV-1 exposed infants.

Recombinant modified vaccinia virus Ankara expressing HIV-1 antigens (MVA.HIVA) was used in ELISpot assays to monitor HIV-1-specific T cell responses in infants. Responses to MVA.

Subtype C Is associated with increased vaginal shedding of HIV-1.

The prevalence of human immunodeficiency virus (HIV)-1-infected cells and HIV-1 RNA levels in genital secretions and breast milk and the risk of mother-to-child transmission of HIV-1 were compared among subtypes A, C, and D in a Kenyan cohort. Pregnant women infected with subtype C were significantly more likely to shed HIV-1-infected vaginal cells than were those infected with subtype A or D (odds ratio [OR], 3.6 [95% confidence interval {CI}, 1.

Longitudinal assessment of human immunodeficiency virus type 1 (HIV-1)-specific gamma interferon responses during the first year of life in HIV-1-infected infants.

Human immunodeficiency virus type 1 (HIV-1) infection results in different patterns of viral replication in pediatric compared to adult populations. The role of early HIV-1-specific responses in viral control has not been well defined, because most studies of HIV-1-infected infants have been retrospective or cross-sectional. We evaluated the association between HIV-1-specific gamma interferon (IFN-gamma) release from the cells of infants of 1 to 3 months of age and peak viral loads and mortality in the first year of life among 61 Kenyan HIV-1-infected infants.

Antenatal couple counseling increases uptake of interventions to prevent HIV-1 transmission.

To determine effect of partner involvement and couple counseling on uptake of interventions to prevent HIV-1 transmission, women attending a Nairobi antenatal clinic were encouraged to return with partners for voluntary HIV-1 counseling and testing (VCT) and offered individual or couple posttest counseling. Nevirapine was provided to HIV-1-seropositive women and condoms distributed to all participants. Among 2104 women accepting testing, 308 (15%) had partners participate in VCT, of whom 116 (38%) were couple counseled.

Association of levels of HIV-1-infected breast milk cells and risk of mother-to-child transmission.

Understanding how the level of human immunodeficiency virus type 1 (HIV-1)-infected breast milk cells (BMCs) affects HIV transmission via breast-feeding can shed light on the mechanism of infection and aid in establishing effective interventions. The proportion of infected cells to total cells was measured in serial breast milk samples collected from 291 HIV-1-infected women in Nairobi, Kenya, by use of real-time DNA polymerase chain reaction amplification of BMCs. The number of infected BMCs per million cells was associated with levels of cell-free viral RNA in breast milk (R=.

Human leukocyte antigen (HLA) B*18 and protection against mother-to-child HIV type 1 transmission.

Human leukocyte antigen (HLA) molecules regulate the cellular immune system and may be determinants of infant susceptibility to human immunodeficiency virus type 1 (HIV-1) infection. Molecular HLA typing for class I alleles was performed on infants followed in a Kenyan perinatal cohort. Early HIV-1 infection status was defined as infection occurring at birth or month 1, while late infection via breast milk was defined as first detection of HIV-1 after 1 month of age.

Predictors of early mortality in a cohort of human immunodeficiency virus type 1-infected african children.

Background: Pediatric human immunodeficiency virus type 1 (HIV-1) infection follows a bimodal clinical course with rapid progression in 10-45% of children before the age of 2 years and slower progression in the remainder. A prospective observational study was undertaken to determine predictors of mortality in HIV-1-infected African infants during the first 2 years of life.

Methods: Infants in a perinatal cohort identified to be HIV-1-infected by DNA PCR were followed monthly to 1 year, then quarterly to 2 years or death.

Breast-feeding and Transmission of HIV-1.

Breast-feeding substantially increases the risk of HIV-1 transmission from mother to child, and although peripartum antiretroviral therapy prophylaxis significantly decreases the risk of mother-to-child transmission around the time of delivery, this approach does not affect breast-feeding transmission. Increased maternal RNA viral load in plasma and breast milk is strongly associated with increased risk of transmission through breast-feeding, as is breast health, and it has been suggested that exclusive breast-feeding could be associated with lower rates of breast-feeding transmission than mixed feeding of both breast- and other milk or feeds. Transmission through breast-feeding can take place at any point during lactation, and the cumulative probability of acquisition of infection increases with duration of breast-feeding.

Infant feeding practices of women in a perinatal HIV-1 prevention study in Nairobi, Kenya.

Objective: To determine feeding practices and nutritional status of infants born to HIV-1-infected women.

Methods: Feeding plans and practices were evaluated by questionnaires and focus group discussions. Infants were weighed at 1 and 6 weeks and tested for HIV-1 at 6 weeks.

Prevalence and magnitude of human immunodeficiency virus (HIV) type 1-specific lymphocyte responses in breast milk from HIV-1-seropositive women.

Human immunodeficiency virus (HIV) type 1-specific cell-mediated immunity of breast milk may influence the likelihood of mother-to-child transmission of HIV-1 via breast-feeding. In breast-milk specimens collected during the first month postpartum from HIV-1-seropositive women in Nairobi, HIV-1 gag-specific cellular responses were detected in 17 (47%) of 36, and env-specific cellular responses were present in 20 (40%) of 50. Peripheral blood lymphocyte responses against either gag or env were detected in 35 (66%) of the 53 subjects, 18 (51%) of whom had positive gag or env responses in their breast milk.