Human milk galectin-3 binding protein and breast-feeding-associated HIV transmission.

Analysis of milk from 247 HIV-infected Zambian mothers showed that galectin-3 binding protein concentrations were significantly higher among HIV-infected mothers who transmitted HIV through breast-feeding (6.51 ± 2.12 μg/mL) than among nontransmitters but were also correlated with higher milk and plasma HIV RNA copies/mL and lower CD4+ cell counts.

HIV-1 concentrations in human breast milk before and after weaning.

Concentrations of HIV-1 RNA and DNA in mucosal compartments influence the risk of sexual transmission and mother-to-child transmission of HIV-1. Breast milk production is physiologically regulated such that supply is a function of infant demand, but whether demand also influences HIV-1 dynamics in breast milk is unknown. We tested whether minor and major changes in feeding frequency influence breast milk viral concentrations in 958 HIV-1-infected women and their infants followed, for 24 months during a trial in Lusaka, Zambia.

Coverage of primary mother-to-child HIV transmission isolates by second-generation broadly neutralizing antibodies.

Objectives And Design: A vaccine capable of providing cross-clade, sterilizing protection has been the holy grail of HIV-1 prevention and control since the beginning of the pandemic. A major component of this effort has been the identification and characterization of broadly neutralizing antibodies (bNAbs). Recent advances in bNAb isolation, structure-based engineering, and vector-mediated gene transfer have led to increased interest in bypassing the immune system by expressing neutralizing antibodies directly in muscle.

Dynamics of breast milk HIV-1 RNA with unilateral mastitis or abscess.

Background: Mastitis and abscess in HIV-infected women increase the risk of breastfeeding transmission of HIV. Guidelines encourage women to stop breastfeeding on the affected breast and feed on the contralateral breast. However, impact of breast pathology on breast milk HIV dynamics is unknown.

Pregnancy loss and role of infant HIV status on perinatal mortality among HIV-infected women.

Background: HIV-infected women, particularly those with advanced disease, may have higher rates of pregnancy loss (miscarriage and stillbirth) and neonatal mortality than uninfected women. Here we examine risk factors for these adverse pregnancy outcomes in a cohort of HIV-infected women in Zambia considering the impact of infant HIV status.

Methods: A total of 1229 HIV-infected pregnant women were enrolled (2001-2004) in Lusaka, Zambia and followed to pregnancy outcome.

Human milk oligosaccharide concentration and risk of postnatal transmission of HIV through breastfeeding.

Background: The inefficiency of HIV breast-milk transmission may be caused by the presence of immunologically active factors, including human milk oligosaccharides (HMOs).

Objective: We investigated whether HMO concentrations are associated with a reduced risk of postnatal HIV transmission.

Design: A nested case-control study was conducted within a larger cohort study of HIV-infected women and their infants followed from birth to 24 mo in Lusaka, Zambia.

'Worse than HIV' or 'not as serious as other diseases'? Conceptualization of cervical cancer among newly screened women in Zambia.

Invasive cervical cancer is the second most common cancer among women worldwide, with approximately 85% of the disease burden occurring in developing countries. To date, there have been few systematic efforts to document African women's conceptualization of cervical cancer after participation in a visual inspection with acetic acid (VIA)-based "see and treat" cervical cancer prevention program. In this study, conducted between September, 2009-July, 2010, focus groups and in-depth interviews were conducted with 60 women who had recently undergone cervical cancer screening at a government-operated primary health care clinic in Lusaka, Zambia.

Motivations and experiences of women who accessed "see and treat" cervical cancer prevention services in Zambia.

Background: In Zambia, a country with a generalized HIV epidemic, age-adjusted cervical cancer incidence is among the highest worldwide. In 2006, the University of Alabama at Birmingham-Center for Infectious Disease Research in Zambia and the Zambian Ministry of Health launched a visual inspection with acetic acid (VIA) -based "see and treat" cervical cancer prevention program in Lusaka. All services were integrated within existing government-operated primary health care facilities.

Exclusive breastfeeding, maternal HIV disease, and the risk of clinical breast pathology in HIV-infected, breastfeeding women.

Objective: The objective of the study was to examine the relationship between breastfeeding patterns, markers of maternal human immunodeficiency virus (HIV) disease, and woman's breast pathology.

Study Design: Secondary data analysis from a randomized breastfeeding trial including 947 HIV-infected women (n = 5982 visits) from breastfeeding initiation until 6 months postpartum; 1 month after breastfeeding cessation; or loss to follow-up or death. Generalized estimating equations assessed the effects of breastfeeding pattern and maternal HIV status on breast pathology.

Early weaning increases diarrhea morbidity and mortality among uninfected children born to HIV-infected mothers in Zambia.

Background: Early weaning may reduce human immunodeficiency virus (HIV) transmission but may have deleterious consequences for uninfected children. Here we evaluate effects of early weaning on diarrhea morbidity and mortality of uninfected children born to HIV-infected mothers.

Methods: HIV-infected women in Lusaka, Zambia, were randomly assigned to breastfeeding for 4 months only or to continue breastfeeding until the mother decided to stop.

Multiple independent lineages of HIV-1 persist in breast milk and plasma.

Design: the origin and evolution of HIV-1 in breast milk is unclear, despite the continuing significance of this tissue as a transmitting compartment. To elucidate the evolutionary trajectory of viral populations in a transient mucosal compartment, longitudinal sequences of the envelope glycoprotein (gp120) region from plasma and breast milk spanning the first year after delivery were analyzed in six women infected by HIV-1 subtype C.

Methods: multiple phylogenetic algorithms were used to elucidate the evolutionary history and spatial structure of virus populations between tissues.

Safety of artemether-lumefantrine in pregnant women with malaria: results of a prospective cohort study in Zambia.

Background: Safety data regarding exposure to artemisinin-based combination therapy in pregnancy are limited. This prospective cohort study conducted in Zambia evaluated the safety of artemether-lumefantrine (AL) in pregnant women with malaria.

Methods: Pregnant women attending antenatal clinics were assigned to groups based on the drug used to treat their most recent malaria episode (AL vs.

Potential impact of new WHO criteria for antiretroviral treatment for prevention of mother-to- child HIV transmission.

We reviewed the potential impact of new WHO criteria for antiretroviral therapy using data from 1025 HIV-infected women and infants followed for 24 months in Lusaka, Zambia. The new criteria require initiating therapy among 68% of pregnant women and, if fully effective, would prevent 92% of maternal deaths and 88% of perinatal and postnatal infections. Using CD4 cell count below 350 cells/microl, irrespective of clinical stage, is more efficient and stricter CD4 cutoffs would be counter productive.

Peripartum nevirapine exposure and subsequent clinical outcomes among HIV-infected women receiving antiretroviral therapy for at least 12 months.

Objective: Prior exposure to intrapartum/neonatal nevirapine (NVP) is associated with compromised virologic treatment outcomes once non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) is initiated. We examined the longer-term clinical outcomes in a programmatic setting.

Methods: We compared post-12 month mortality and clinical treatment failure (defined by WHO clinical and immunologic criteria) among women with and without prior NVP exposure in Lusaka, Zambia.

Lactation-associated postpartum weight changes among HIV-infected women in Zambia.

Background: There are concerns about effects of lactation on postpartum weight changes among HIV-infected women because low weight may increase risks of HIV-related disease progression.

Methods: This analysis of postpartum maternal weight change is based on a trial evaluating the effects of shortened breastfeeding on postpartum mother-to-child transmission of HIV in Lusaka, Zambia, in which 958 HIV-infected women were randomized to breastfeed for a short duration (4 months) or for a duration of their own informed choosing (median 16 months). Among 768 women who met inclusion criteria, we compared across the two groups change in weight (kg) and the percent underweight [body mass index (BMI) <18.

Methods and baseline results of a repeated cross-sectional survey to assess the public health impact of antiretroviral therapy in Lusaka, Zambia.

Although the individual-level impact of antiretroviral therapy (ART) is well documented, there are few available data describing the public health impact of services for persons infected with human immunodeficiency virus in resource-constrained settings. We describe the methods and baseline results of a household survey that assessed the population-level impact of the national program for HIV care in Zambia and treatment in the city of Lusaka. The survey was timed with the staggered expansion of services and repeated cross-sectional surveys planned for pre-implementation and post-implementation comparisons made by community.

Restriction of HIV-1 genotypes in breast milk does not account for the population transmission genetic bottleneck that occurs following transmission.

Background: Breast milk transmission of HIV-1 remains a major route of pediatric infection. Defining the characteristics of viral variants to which breastfeeding infants are exposed is important for understanding the genetic bottleneck that occurs in the majority of mother-to-child transmissions. The blood-milk epithelial barrier markedly restricts the quantity of HIV-1 in breast milk, even in the absence of antiretroviral drugs.

4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms.

Human antibody 4E10 targets the highly conserved membrane-proximal external region (MPER) of the HIV-1 transmembrane glycoprotein, gp41, and has extraordinarily broad neutralizing activity. It is considered by many to be a prototype for vaccine development. In this study, we describe four subjects infected with viruses carrying rare MPER polymorphisms associated with resistance to 4E10 neutralization.

Couples' voluntary counselling and testing and nevirapine use in antenatal clinics in two African capitals: a prospective cohort study.

Background: With the accessibility of prevention of mother to child transmission (PMTCT) services in sub-Saharan Africa, more women are being tested for HIV in antenatal care settings. Involving partners in the counselling and testing process could help prevent horizontal and vertical transmission of HIV. This study was conducted to assess the feasibility of couples' voluntary counseling and testing (CVCT) in antenatal care and to measure compliance with PMTCT.

Elevations in mortality associated with weaning persist into the second year of life among uninfected children born to HIV-infected mothers.

Background: Early weaning has been recommended to reduce postnatal human immunodeficiency virus (HIV) transmission. We evaluated the safety of stopping breast-feeding at different ages for mortality of uninfected children born to HIV-infected mothers.

Methods: During a trial of early weaning, 958 HIV-infected mothers and their infants were recruited and followed up from birth to 24 months postpartum in Lusaka, Zambia.

HIV prevention is not enough: child survival in the context of prevention of mother to child HIV transmission.

Clinical and epidemiologic research has identified increasingly effective interventions to reduce mother to child HIV transmission in resource-limited settings These scientific breakthroughs have been implemented in some programmes, although much remains to be done to improve coverage and quality of these programmes. But prevention of HIV transmission is not enough. It is necessary also to consider ways to improve maternal health and protect child survival.

A cluster-randomized trial of enhanced labor ward-based PMTCT services to increase nevirapine coverage in Lusaka, Zambia.

Objective: Determine whether enhanced labor ward-based services for prevention of mother-to-child transmission of HIV (PMTCT) would improve nevirapine (NVP) coverage.

Design: Cluster-randomized trial at 12 public-sector delivery centers in Lusaka, Zambia.

Methods: Following a baseline surveillance period, 12 labor wards were randomized, six to offer opt-in HIV testing to women of unknown serostatus (with NVP administration as indicated) and to assess NVP adherence among known HIV-infected women.

Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention.

A single dose of tenofovir/emtricitabine (TDF/FTC) during labor significantly reduces peripartum nevirapine-associated viral drug resistance when measured by consensus HIV sequencing. It is unknown whether this effect extends to HIV subpopulations of <25-50%. We conducted a randomized trial of single-dose TDF/FTC added to peripartum nevirapine to reduce drug resistance associated with nonnucleoside reverse transcriptase inhibitors (NNRTIs).

High concentrations of interleukin 15 in breast milk are associated with protection against postnatal HIV transmission.

Given the central role that interleukin 15 (IL-15) plays in human immunodeficiency virus (HIV) immunity, we hypothesized that IL-15 in breast milk may protect against postnatal HIV transmission. In a nested case-control study, we compared breast milk IL-15 levels in 22 HIV-infected women who transmitted HIV to their infants to those in 72 nontransmitters. Samples were collected in the first month of life, prior to HIV infection.

Detection of low levels of human immunodeficiency virus (HIV) may be critical for early diagnosis of pediatric HIV infection by use of dried blood spots.

We compared a DNA-based assay with a total nucleic acid-based assay for early detection of infant human immunodeficiency virus (HIV) infection. The codetection of DNA and RNA did not result in an overall higher sensitivity compared to that of DNA alone. Discordant results were associated with low levels of HIV DNA, indicating that the sample amount may be critical.