Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

<p>Introduction - Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.</p> <p>Materials and Methods - Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.</p> <p>Results - There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].</p> <p>Conclusions - The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.</p&gt

Antenatal HIV-1 RNA load and timing of mother to child transmission; a nested case-control study in a resource poor setting

<p>Abstract</p> <p>Objective</p> <p>To determine HIV-1 RNA load during the third trimester of pregnancy and evaluate its effect on <it>in utero </it>and intra-partum/postpartum transmissions in a breastfeeding population.</p> <p>Design</p> <p>A nested case-control study within a PMTCT cohort of antiretroviral therapy naive pregnant women and their infants.</p> <p>Methods</p> <p>A case was a mother who transmitted HIV-1 to her infant (transmitter) who was matched to one HIV-1 positive but non-transmitting mother (control).</p> <p>Results</p> <p>From a cohort of 691 pregnant women, 177 (25.6%) were HIV-1 positive at enrolment and from these 29 (23%) transmitted HIV-1 to their infants, 10 and 19 during <it>in utero </it>and intra-partum/postpartum respectively. Twenty-four mothers sero-converted after delivery and three transmitted HIV-1 to their infants. Each unit increase in log₁₀viral load was associated with a 178 cells/mm³and 0.2 g/dL decrease in TLC and hemoglobin levels, p = 0.048 and 0.021 respectively, and a 29% increase in the risk of transmission, p = 0.023. Intra-partum/postpartum transmitters had significantly higher mean viral load relative to their matched controls, p = 0.034.</p> <p>Conclusion</p> <p>Antenatal serum HIV-1 RNA load, TLC and hemoglobin levels were significantly associated with vertical transmission but this association was independent of transmission time. This finding supports the rationale for preventive strategies designed to reduce vertical transmission by lowering maternal viral load.</p

Infant feeding among HIV-positive mothers and the general population mothers: comparison of two cross-sectional surveys in Eastern Uganda

<p>Abstract</p> <p>Background</p> <p>Infant feeding recommendations for HIV-positive mothers differ from recommendations to mothers of unknown HIV-status. The aim of this study was to compare feeding practices, including breastfeeding, between infants and young children of HIV-positive mothers and infants of mothers in the general population of Uganda.</p> <p>Methods</p> <p>This study compares two cross-sectional surveys conducted in the end of 2003 and the beginning of 2005 in Eastern Uganda using analogous questionnaires. The first survey consisted of 727 randomly selected general-population mother-infant pairs with unknown HIV status. The second included 235 HIV-positive mothers affiliated to The Aids Support Organisation, TASO. In this article we compare early feeding practices, breastfeeding duration, feeding patterns with dietary information and socio-economic differences in the two groups of mothers.</p> <p>Results</p> <p>Pre-lacteal feeding was given to 150 (64%) infants of the HIV-positive mothers and 414 (57%) infants of general-population mothers. Exclusive breastfeeding of infants under the age of 6 months was more common in the general population than among the HIV-positive mothers (186 [45%] vs. 9 [24%] respectively according to 24-hour recall). Mixed feeding was the most common practice in both groups of mothers. Solid foods were introduced to more than half of the infants under 6 months old among the HIV-positive mothers and a quarter of the infants in the general population. Among the HIV-positive mothers with infants below 12 months of age, 24 of 90 (27%) had stopped breastfeeding, in contrast to 9 of 727 (1%) in the general population. The HIV-positive mothers were poorer and had less education than the general-population mothers.</p> <p>Conclusion</p> <p>In many respects, HIV-positive mothers fed their infants less favourably than mothers in the general population, with potentially detrimental effects on both the child's nutrition and the risk of HIV transmission. Mixed feeding and pre-lacteal feeding were widespread. Breastfeeding duration was shorter among HIV-positive mothers. Higher educational level and being socio-economically better off were associated with more beneficial infant feeding practices.</p

Reproductive Intentions and Outcomes among Women on Antiretroviral Therapy in Rural Uganda: A Prospective Cohort Study

Background: Antiretroviral therapy (ART) may influence the biological, social and behavioral determinants of pregnancy in HIV-infected women. However, there are limited longitudinal data on the reproductive intentions and outcomes among women on ART in Africa. Methodology /Principal Findings: Using a prospective cohort design, we analyzed trends in desire for children and predictors of pregnancy among a cohort of 733 HIV-infected women in rural Uganda who initiated ART between May 2003 and May 2004 and were followed up in their homes until June 2006. Women answered in-depth social and behavioral questionnaires administered every quarter in year 1 after initiating ART, and every 6 to 12 months thereafter. Use of family planning methods was assessed at 18 and 24 months after starting ART. We tested for non-constant pregnancy incidence by using a shape parameter test from the Weibull distribution. We modeled repeated measurements of all variables related to the women’s desire for children over time using a generalized estimating equation (GEE) extension to the logistic regression model. Risk factors for pregnancy were examined using Cox proportional hazards model. 711 women eligible for the study were followed-up for a median time of 2.4 years after starting ART. During this time, less than 7 % of women reported wanting more children at any time point yet 120 (16.9%) women experienced 140 pregnancies and pregnancy incidence increased from 3.46 per 100 women-years (WY) in the first quarter to 9.5 per 100 WY at 24 months (p,0.0001). This wa

Binding of Human Milk to Pathogen Receptor DC-SIGN Varies with Bile Salt-Stimulated Lipase (BSSL) Gene Polymorphism

OBJECTIVE: Dendritic cells bind an array of antigens and DC-SIGN has been postulated to act as a receptor for mucosal pathogen transmission. Bile salt-stimulated lipase (BSSL) from human milk potently binds DC-SIGN and blocks DC-SIGN mediated trans-infection of CD4(+) T-lymphocytes with HIV-1. Objective was to study variation in DC-SIGN binding properties and the relation between DC-SIGN binding capacity of milk and BSSL gene polymorphisms. STUDY DESIGN: ELISA and PCR were used to study DC-SIGN binding properties and BSSL exon 11 size variation for human milk derived from 269 different mothers distributed over 4 geographical regions. RESULTS: DC-SIGN binding properties were highly variable for milks derived from different mothers and between samplings from different geographical regions. Differences in DC-SIGN binding were correlated with a genetic polymorphism in BSSL which is related to the number of 11 amino acid repeats at the C-terminus of the protein. CONCLUSION: The observed variation in DC-SIGN binding properties among milk samples may have implications for the risk of mucosal transmission of pathogens during breastfeeding

Distinct Kinetics of Memory B-Cell and Plasma-Cell Responses in Peripheral Blood Following a Blood-Stage Plasmodium chabaudi Infection in Mice

B cell and plasma cell responses take place in lymphoid organs, but because of the inaccessibility of these organs, analyses of human responses are largely performed using peripheral blood mononuclear cells (PBMC). To determine whether PBMC are a useful source of memory B cells and plasma cells in malaria, and whether they reflect Plasmodium-specific B cell responses in spleen or bone marrow, we have investigated these components of the humoral response in PBMC using a model of Plasmodium chabaudi blood-stage infections in C57BL/6 mice. We detected memory B cells, defined as isotype-switched IgD− IgM− CD19+ B cells, and low numbers of Plasmodium chabaudi Merozoite Surface Protein-1 (MSP1)-specific memory B cells, in PBMC at all time points sampled for up to 90 days following primary or secondary infection. By contrast, we only detected CD138+ plasma cells and MSP1-specific antibody-secreting cells within a narrow time frame following primary (days 10 to 25) or secondary (day 10) infection. CD138+ plasma cells in PBMC at these times expressed CD19, B220 and MHC class II, suggesting that they were not dislodged bone-marrow long-lived plasma cells, but newly differentiated migratory plasmablasts migrating to the bone marrow; thus reflective of an ongoing or developing immune response. Our data indicates that PBMC can be a useful source for malaria-specific memory B cells and plasma cells, but extrapolation of the results to human malaria infections suggests that timing of sampling, particularly for plasma cells, may be critical. Studies should therefore include multiple sampling points, and at times of infection/immunisation when the B-cell phenotypes of interest are likely to be found in peripheral blood

What Will It Take to Eliminate Pediatric HIV? Reaching WHO Target Rates of Mother-to-Child HIV Transmission in Zimbabwe: A Model-Based Analysis

Using a simulation model, Andrea Ciaranello and colleagues find that the latest WHO PMTCT (prevention of mother to child transmission of HIV) guidelines plus better access to PMTCT programs, better retention of women in care, and better adherence to drugs are needed to eliminate pediatric HIV in Zimbabwe