HIV-free Survival Research Articles

Infant-feeding practices of HIV-positive mothers in the south west region of Cameroon

Prevention of Mother to Child Transmission (PMTCT) of HIV is of great importance, because vertical transmission, including breastfeeding, accounts for the majority of pediatric HIV infections. Appropriate infant feeding methods which are affordable, feasible, acceptable, safe and sustainable are therefore crucial to the healthy HIV-free survival of HIV exposed infants. This study aimed at determining the proportions of mothers practising the various feeding methods, determining the various factors influencing these feeding methods, and ascertaining the relationship between these factors and the chosen feeding modes. A cross-sectional observational study was carried out from April 2012 to July 2012; using structured questionnaires administered to one hundred and ten HIV positive mothers attending infant welfare clinics. Exclusive Breastfeeding (EBF) was found to be the predominant mode of feeding chosen (70%), followed by Replacement Feeding (RF) and Mixed Feeding (MF), each representing 15%. EBF and RF practices were highly influenced by mother’s personal choice and secondly, the Health Care Provider (HCP). Choosing EBF during Antenatal Care (ANC) and being married were the main predictors of EBF. RF was associated with disclosure of HIV status to partner. MF commonly resulted from ignorance, financial difficulties and fear of stigmatization. Predictors of MF included maternal age ≤25, having an unemployed partner, non-disclosure of HIV status to family, attending ANC at Health Centre, choosing RF during ANC, and not receiving Anti-retroviral drugs during pregnancy. EBF was the most common mode of feeding, as most mothers stuck to their informed safe choices, despite the fact that good feeding practices were being challenged by social stigma. To discourage unsafe feeding practices, much needs to be done to fight stigmatization amongst HIV-infected mothers, which includes encouraging them to disclose their HIV statuses to close family partner(s), while encouraging comprehensive antenatal care.

Clinical Outcomes of a Comprehensive Integrated Program for HIV-Exposed Infants

Prevention of mother-to-child transmission of HIV services are often inadequate in promoting HIV-free child survival in rural areas with limited resources. An integrated comprehensive child survival program in rural Rwanda with special emphasis on HIV-exposed infants was established in 2005 and scaled-up. The objective of this study was to report program outcomes and identify predictors of program retention. We conducted a retrospective study of infants born to HIV-infected women enrolled in the program at or before birth from March 1, 2007, to February 28, 2010, in Eastern Rwanda. Key program elements included improved access to health care, antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV, clean water sources and replacement feeding, home visits by community health workers, prevention and treatment of childhood illness, nutritional support, family planning, and socioeconomic support for the extremely vulnerable. Overall,1038 infants enrolled in the program in the study period during which time there was a 4-fold increase in the number of current participants. Uptake of contraception and treatment for diarrheal disease were high. The 18-month survival probability and retention probability were 0.93 (95% confidence interval: 0.91 to 0.94) and 0.88 (95% confidence interval: 0.86 to 0.90), respectively. Twenty-seven (2.6%) children tested positive for HIV, of which 1 died and none were lost-to-follow-up at 18 months. No statistically significant predictors of retention were identified. Our findings demonstrate that a comprehensive integrated program to promote HIV-free survival can achieve high rates of retention and survival in a highly vulnerable population, even during a period of rapid growth.

Effect of Highly Active Antiretroviral Treatment (HAART) During Pregnancy on Pregnancy Outcomes: Experiences from a PMTCT Program in Western India

Previous research regarding the effect of highly active antiretroviral treatment (HAART) on pregnancy outcomes shows conflicting results and is predominantly situated in developed countries. Recently, HAART is rapidly being scaled up in developing countries for prevention of mother-to-child transmission (PMTCT). This study compared adverse pregnancy outcomes among HIV infected women (N=516) who received either HAART (N=192)--mostly without protease inhibitor--or antepartum azidothymidine (AZT) with intrapartum nevirapine (N=324) from January 2008 to March 2012 through a PMTCT program in western India. We analyzed the effect of HAART on preterm births, low birth weight, and all adverse pregnancy outcomes combined using univariate and multivariate logistic regression models. Women on HAART had 48% adverse pregnancy outcomes, 25% preterm births, and 34% low birth weight children compared to respectively 32%, 13%, and 22% among women on AZT. Women receiving HAART were more likely to have adverse pregnancy outcomes and preterm births compared to women receiving AZT. Preconception HAART was significantly related to low birth weight children. This study demonstrated increased risk of adverse pregnancy outcomes with protease inhibitor excluded HAART. Prospective studies assessing the impact of HAART on MTCT as measured in terms of HIV-free survival among children are needed.

Prevention of mother-to-child transmission of HIV: cost-effectiveness of antiretroviral regimens and feeding options in Rwanda.

BackgroundRwanda's National PMTCT program aims to achieve elimination of new HIV infections in children by 2015. In November 2010, Rwanda adopted the WHO 2010 ARV guidelines for PMTCT recommending Option B (HAART) for all HIV-positive pregnant women extended throughout breastfeeding and discontinued (short course-HAART) only for those not eligible for life treatment. The current study aims to assess the cost-effectiveness of this policy choice.MethodsBased on a cohort of HIV-infected pregnant women in Rwanda, we modelled the cost-effectiveness of six regimens: dual ARV prophylaxis with either 12 months breastfeeding or replacement feeding; short course HAART (Sc-HAART) prophylaxis with either 6 months breastfeeding, 12 months breastfeeding, or 18 months breastfeeding; and Sc-HAART prophylaxis with replacement feeding. Direct costs were modelled based on all inputs in each scenario and related unit costs. Effectiveness was evaluated by measuring HIV-free survival at 18 months. Savings correspond to the lifetime costs of HIV treatment and care avoided as a result of all vertical HIV infections averted.ResultsAll PMTCT scenarios considered are cost saving compared to “no intervention.” Sc-HAART with 12 months breastfeeding or 6 months breastfeeding dominate all other scenarios. Sc-HAART with 12 months breastfeeding allows for more children to be alive and HIV-uninfected by 18 months than Sc-HAART with 6 months breastfeeding for an incremental cost per child alive and uninfected of 11,882 USD. This conclusion is sensitive to changes in the relative risk of mortality by 18 months for exposed HIV-uninfected children on replacement feeding from birth and those who were breastfed for only 6 months compared to those breastfeeding for 12 months or more.ConclusionOur findings support the earlier decision by Rwanda to adopt WHO Option B and could inform alternatives for breastfeeding duration. Local contexts and existing care delivery models should be part of national policy decisions.

Effects of postnatal interventions for the reduction of vertical HIV transmission on infant growth and non‐HIV infections: a systematic review

IntroductionGuidelines in resource-poor settings have progressively included interventions to reduce postnatal HIV transmission through breast milk. In addition to HIV-free survival, infant growth and non-HIV infections should be considered. Determining the effect of these interventions on infant growth and non-HIV infections will inform healthcare decisions about feeding HIV-exposed infants. We synthesize findings from studies comparing breast to formula feeding, early weaning to standard-duration breastfeeding, breastfeeding with extended antiretroviral (ARV) to short-course ARV prophylaxis, and alternative preparations of infant formula to standard formula in HIV-exposed infants, focusing on infant growth and non-HIV infectious morbidity outcomes. The review objectives were to collate and appraise evidence of interventions to reduce postnatal vertical HIV transmission, and to estimate their effect on growth and non-HIV infections from birth to two years of age among HIV-exposed infants.MethodsWe searched PubMed, SCOPUS, and Cochrane CENTRAL Controlled Trials Register. We included randomized trials and prospective cohort studies. Two authors independently extracted data and evaluated risk of bias. Rate ratios and mean differences were used as effect measures for dichotomous and continuous outcomes, respectively. Where pooling was possible, we used fixed-effects meta-analysis to pool results across studies. Quality of evidence was assessed using the GRADE approach.Results and discussionProspective cohort studies comparing breast- versus formula-fed HIV-exposed infants found breastfeeding to be protective against diarrhoea in early life [risk ratio (RR)=0.31; 95% confidence interval (CI)=0.13 to 0.74]. The effect of breastfeeding against diarrhoea [hazard ratio (HR)=0.74; 95% CI=0.57 to 0.97] and respiratory infections (HR=0.65; 95% CI=0.41 to 1.00) was significant through two years of age. The only randomized controlled trial (RCT) available showed that breastfeeding tended to be protective against malnutrition (RR=0.63; 95% CI=0.36 to 1.12). We found no statistically significant differences in the rates of non-HIV infections or malnutrition between breast-fed infants in the extended and short-course ARV prophylaxis groups.ConclusionsLow to moderate quality evidence suggests breastfeeding may improve growth and non-HIV infection outcomes of HIV-exposed infants. Extended ARV prophylaxis does not appear to increase the risk for HIV-exposed infants for adverse growth or non-HIV infections compared to short-course ARV prophylaxis.

The Study of HIV and Antenatal Care Integration in Pregnancy in Kenya: Design, Methods, and Baseline Results of a Cluster-Randomized Controlled Trial

BackgroundDespite strong evidence for the effectiveness of anti-retroviral therapy for improving the health of women living with HIV and for the prevention of mother-to-child transmission (PMTCT), HIV persists as a major maternal and child health problem in sub-Saharan Africa. In most settings antenatal care (ANC) services and HIV treatment services are offered in separate clinics. Integrating these services may result in better uptake of services, reduction of the time to treatment initiation, better adherence, and reduction of stigma.Methodology/Principal FindingsA prospective cluster randomized controlled trial design was used to evaluate the effects of integrating HIV treatment into ANC clinics at government health facilities in rural Kenya. Twelve facilities were randomized to provide either fully integrated services (ANC, PMTCT, and HIV treatment services all delivered in the ANC clinic) or non-integrated services (ANC clinics provided ANC and basic PMTCT services and referred clients to a separate HIV clinic for HIV treatment). During June 2009– March 2011, 1,172 HIV-positive pregnant women were enrolled in the study. The main study outcomes are rates of maternal enrollment in HIV care and treatment, infant HIV testing uptake, and HIV-free infant survival. Baseline results revealed that the intervention and control cohorts were similar with respect to socio-demographics, male partner HIV testing, sero-discordance of the couple, obstetric history, baseline CD4 count, and WHO Stage. Challenges faced while conducting this trial at low-resource rural health facilities included frequent staff turnover, stock-outs of essential supplies, transportation challenges, and changes in national guidelines.Conclusions/SignificanceThis is the first randomized trial of ANC and HIV service integration to be conducted in rural Africa. It is expected that the study will provide critical evidence regarding the implementation and effectiveness of this service delivery strategy, with important implications for programs striving to eliminate vertical transmission of HIV and improve maternal health.Trial RegistrationClinicalTrials.gov NCT00931216 NCT00931216.

Use of service data to inform pediatric HIV-free survival following prevention of mother-to-child transmission programs in rural Malawi

BackgroundRecent years have seen rapid and significant progress in science and implementation of programs to prevent mother-to-child transmission of HIV. Programs that support PMTCT routinely monitor service provision but very few have measured their effectiveness. The objective of the study was to use service data to inform HIV-free survival among HIV exposed children that received antiretroviral drugs to prevent mother-to-child transmission (PMTCT) of HIV. The study was conducted in two rural districts in Malawi with support from FHI 360.MethodsA descriptive observational study of PMTCT outcomes was conducted between June 2005 and June 2009. The dataset included patient-level data of all pregnant women 1) that tested HIV-positive, 2) that were dispensed with antiretroviral prophylaxis, and 3) whose addresses were available for home visits. The data were matched to each woman’s corresponding antenatal clinic data from home visit registers.ResultsOut of 438 children whose home addresses were available, 33 (8%) were lost to follow-up, 35 (8%) were alive but not tested for HIV by the time home visit was conducted, and 52 (12%) were confirmed deceased. A total of 318 children were alive at the time of the home visit and had an HIV antibody test done at median age 15 months. The resulting estimated 24-month probability of HIV-free survival over all children was 78%. Among children who did not receive nevirapine, the estimated 24-month probability of HIV-free survival was 61%, and among those who did receive NVP syrup the estimate was 82%.ConclusionsWhen mothers and newborns received nevirapine, the estimated 24-month probability of HIV-free survival among children was high at 82% (CI: 54% to 99%). However this conclusion should be interpreted cautiously 1) due to the wide confidence interval; and 2) because the confidence interval range includes 55%, which is the natural HIV-free survival rate in the absence of a PMTCT intervention. This analysis highlighted the need of quality data and well-structured home visits to assess PMTCT effectiveness.

Use of Service Data to Inform Pediatric HIV-free Survival Following Prevention of Mother-to-Child Transmission Programs in Rural Malawi

Use of Service Data to Inform Pediatric HIV-free Survival Following Prevention of Mother-to-Child Transmission Programs in Rural Malawi

Care of the HIV-Exposed Child—To Breast Feed or Not?

Breast milk is the best form of nutrition for infants. However, it places infants born to HIV infected women at risk of acquiring HIV infection. Total avoidance of breastfeeding is the only way of completely avoiding HIV transmission through breast milk. However, this strategy has not proved to be viable in resource constrained nations. A high infection related mortality and morbidity, and a high prevalence of malnutrition have been observed in HIV exposed infants on replacement feeding. Exclusive breastfeeding for the first six months followed by rapid weaning has also not proved to be a good strategy, with a surge in infection related morbidity and malnutrition reported after weaning. Current evidence indicates that continued use of ARV prophylaxis to mother/infant starting during pregnancy and continued to cover the entire duration of breastfeeding offers the infant best chance of HIV free survival, combining the benefits of breast milk with safety induced by ARV prophylaxis.

Nutritional Rehabilitation of HIV-Exposed Infants in Malawi: Results from the Drug Resources Enhancement Against AIDS and Malnutrition Program

Infant malnutrition in sub-Saharan Africa is a public health priority and a challenge in high HIV prevalence areas. The Drug Resources Enhancement Against AIDS and Malnutrition program, with multiple medical centers in Sub-Saharan Africa, developed an innovative intervention for the surveillance and control of malnutrition. In a pilot initiative, 36 HIV-exposed children were evaluated at baseline upon presentation for malnutrition and at six months post- treatment. Parameters included HIV-free survival, nutritional status and change in diet. Food diary data was entered and processed using the Nutrisurvey (WHO) software. At 6 months post-intervention, a significant improvement in anthropometric parameters was noted. Slowing of linear growth was observed in patients with malaria with a mean gain in centimetres of 4.4 ± 1.7 as compared to 5.6 ± 1.7 in children with no malaria, p < 0.048 (CL 95%: −2.32, −0.01). Dietary diversity scores increased from 5.3 ± 1.9 to 6.5 ± 1.3, p < 0.01 at 6 months. A significant increase (+25%, p < 0.02) in the number of children eating fish meals was noted. Our pilot data describes positive outcomes from a rehabilitative nutritional approach based on use of local foods, peer education, anthropometric and clinical monitoring in areas of high food insecurity. The relationship between malaria and linear growth retardation requires further investigation.

HIV‐free survival among nine‐ to 24‐month‐old children born to HIV‐positive mothers in the Rwandan national PMTCT programme: a community‐based household survey

BackgroundOperational effectiveness of large-scale national programmes for the prevention of mother to child transmission (PMTCT) of HIV in sub-Saharan Africa remains limited. We report on HIV-free survival among nine- to 24-month-old children born to HIV-positive mothers in the national PMTCT programme in Rwanda.MethodsWe conducted a national representative household survey between February and May 2009. Participants were mothers who had attended antenatal care at least once during their most recent pregnancy, and whose children were aged nine to 24 months. A two-stage stratified (geographic location of PMTCT site, maternal HIV status during pregnancy) cluster sampling was used to select mother-infant pairs to be interviewed during household visits. Alive children born from HIV-positive mothers (HIV-exposed children) were tested for HIV according to routine HIV testing protocol. We calculated HIV-free survival at nine to 24 months. We subsequently determined factors associated with mother to child transmission of HIV, child death and HIV-free survival using logistic regression.ResultsOut of 1448 HIV-exposed children surveyed, 44 (3.0%) were reported dead by nine months of age. Of the 1340 children alive, 53 (4.0%) tested HIV positive. HIV-free survival was estimated at 91.9% (95% confidence interval: 90.4-93.3%) at nine to 24 months. Adjusting for maternal, child and health system factors, being a member of an association of people living with HIV (adjusted odds ratio: 0.7, 95% CI: 0.1-0.995) improved by 30% HIV-free survival among children, whereas the maternal use of a highly active antiretroviral therapy (HAART) regimen for PMTCT (aOR: 0.6, 95% CI: 0.3-1.07) had a borderline effect.ConclusionsHIV-free survival among HIV-exposed children aged nine to 24 months is estimated at 91.9% in Rwanda. The national PMTCT programme could achieve greater impact on child survival by ensuring access to HAART for all HIV-positive pregnant women in need, improving the quality of the programme in rural areas, and strengthening linkages with community-based support systems, including associations of people living with HIV.

An effectiveness study of an integrated, community-based package for maternal, newborn, child and HIV care in South Africa: study protocol for a randomized controlled trial

BackgroundProgress towards MDG4 in South Africa will depend largely on scaling up effective prevention against mother to child transmission (PMTCT) of HIV and also addressing neonatal mortality. This imperative drives increasing focus on the neonatal period and particularly on the development and testing of appropriate models of sustainable, community-based care in South Africa in order to reach the poor. A number of key implementation gaps affecting progress have been identified. Implementation gaps for HIV prevention in neonates; implementation gaps for neonatal care especially home postnatal care; and implementation gaps for maternal mental health support. We have developed and are evaluating and costing an integrated and scaleable home visit package delivered by community health workers targeting pregnant and postnatal women and their newborns to provide essential maternal/newborn care as well as interventions for Prevention of Mother to Child Transmission (PMTCT) of HIV.MethodsThe trial is a cluster randomized controlled trial that is being implemented in Umlazi which is a peri-urban settlement with a total population of 1 million close to Durban in KwaZulu Natal, South Africa. The trial consists of 30 randomized clusters (15 in each arm). A baseline survey established the homogeneity of clusters and neither stratification nor matching was performed. Sample size was based on increasing HIV-free survival from 74% to 84%, and calculated to be 120 pregnant women per cluster. Primary outcomes are higher levels of HIV free survival and levels of exclusive and appropriate infant feeding at 12 weeks postnatally. The intervention is home based with community health workers delivering two antenatal visits, a postnatal visit within 48 hours of birth, and a further four visits during the first two months of the infants life. We are undertaking programmatic and cost effectiveness analysis to cost the intervention.DiscussionThe question is not merely to develop an efficacious package but also to identify and test delivery strategies that enable scaling up, which requires effectiveness studies in a health systems context, adapting and testing Asian community-based studies in various African contexts.Trial registrationISRCTN: ISRCTN41046462

Highly Active Antiretroviral Therapy Versus Zidovudine for Prevention of Mother-to-Child Transmission in a Programmatic Setting, Botswana

Few studies have compared the programmatic effectiveness of the recommended strategies of antenatal highly active antiretroviral therapy (HAART) and zidovudine for prevention of mother-to-child transmission. We prospectively followed infants (93% formula fed) whose mothers who took either HAART (258 infants) or zidovudine (170 infants) during pregnancy in the Botswana national program. Overall, 10 infants (2.5%) acquired HIV--9 infants in the zidovudine group (5.5%, 95% confidence interval: 2.6% to 10.2%) and 1 infant in the HAART group (0.4%, 95% confidence interval: 0.0% to 2.2%). Maternal HAART was associated with decreased prevention of mother-to-child transmission (P = 0.001) and improved HIV-free survival (P = 0.040) compared with zidovudine (with or without single-dose nevirapine) in a programmatic setting.

Mother’s CD4+ Count Moderates the Risk Associated with Higher Parity for Late Postnatal HIV-Free Survival of Breastfed Children: An Individual Patient Data Meta-Analysis of Randomized Controlled Trials

Risk association studies of late postnatal outcomes for children breastfed by HIV-1 positive mothers have had inconsistent findings and have not explored interactions among risk factors. This study addresses these limitations through an individual patient data (IPD) meta-analysis of HIV-free survival outcomes of nine randomized controlled trials to prevent early mother-to-child transmission of HIV-1. The pooled sample consisted of 3,324 African children in resource-limited settings who survived to age 28 days and were at-risk of acquiring HIV through breast milk. Based on a proportional hazards mixed effects meta-analysis, the composite endpoint of HIV-1 infection and all-cause mortality was found to be significantly associated with maternal immune status (CD4(+) ≥350 cells/mm(3), HR 0.59 95% CI (0.39, 0.87)), infant preterm delivery (gestational age <37 weeks, 1.40 (1.03, 1.89)), infant oral candidiasis infection (1.87, (1.53, 2.29)), and occurrence of breast abnormality before breastfeeding cessation (2.56 (1.90, 3.46)). A significant interaction between mother's parity (any previous pregnancy) and CD4(+) count ≥350 (HR 0.63 (0.40, 0.99), P-value = 0.045) suggested that higher CD4(+) count offsets the risk associated with higher parity. Further research is needed to elucidate the moderating effect of immune status on the risk associated with high parity and adverse late postnatal outcomes for infants breastfed by HIV-infected mothers in the absence of antiretroviral treatment.

High Human Immunodeficiency Virus-free Survival of Infants Born to Human Immunodeficiency Virus-positive Mothers in an Integrated Program to Decrease Child Mortality in Rural Rwanda

We retrospectively examined infant mortality and human immunodeficiency virus (HIV)-free survival among 211 infants who received a comprehensive package of health services, including breast milk substitution and clean water access, to prevent maternal-to-child transmission of HIV and improve child survival. The cumulative 12-month infant survival probability was 0.97 (95% confidence interval: 0.94-0.99). The cumulative 12- to 18-month HIV-free survival probability was 0.95 (confidence interval: 0.91-0.97).

Uptake and outcomes of a prevention-of mother-to-child transmission (PMTCT) program in Zomba district, Malawi

BackgroundHIV prevalence among pregnant women in Malawi is 12.6%, and mother-to-child transmission is a major route of transmission. As PMTCT services have expanded in Malawi in recent years, we sought to determine uptake of services, HIV-relevant infant feeding practices and mother-child health outcomes.MethodsA matched-cohort study of HIV-infected and HIV-uninfected mothers and their infants at 18-20 months post-partum in Zomba District, Malawi. 360 HIV-infected and 360 HIV-uninfected mothers were identified through registers. 387 mother-child pairs were included in the study.Results10% of HIV-infected mothers were on HAART before delivery, 27% by 18-20 months post-partum. sd-NVP was taken by 75% of HIV-infected mothers not on HAART, and given to 66% of infants. 18% of HIV-infected mothers followed all current recommended PMTCT options. HIV-infected mothers breastfed fewer months than HIV-uninfected mothers (12 vs.18, respectively; p < 0.01). 19% of exposed versus 5% of unexposed children had died by 18-20 months; p < 0.01. 28% of exposed children had been tested for HIV prior to the study, 76% were tested as part of the study and 11% were found HIV-positive. HIV-free survival by 18-20 months was 66% (95%CI 58-74). There were 11(6%) maternal deaths among HIV-infected mothers only.ConclusionThis study shows low PMTCT program efficiency and effectiveness under routine program conditions in Malawi. HIV-free infant survival may have been influenced by key factors, including underuse of HAART, underuse of sd-NVP, and suboptimal infant feeding practices. Maternal mortality among HIV-infected women demands attention; improved maternal survival is a means to improve infant survival.

Twelve-month follow-up of Six Week Extended Dose Nevirapine randomized controlled trials: differential impact of extended-dose nevirapine on mother-to-child transmission and infant death by maternal CD4 cell count

We previously reported combined analysis of 6-week and 6-month endpoints of three randomized controlled trials [Six Week Extended Dose Nevirapine (SWEN) trials] that compared extended-dose nevirapine through 6 weeks of age to single-dose nevirapine to prevent HIV transmission via breastfeeding and mortality. We now present endpoints through 12 months of age. Infants in Ethiopia, India, and Uganda born to HIV-infected women who chose to breastfeed were randomized to receive single-dose or extended-dose nevirapine. HIV transmission, mortality, HIV transmission or death. Primary analysis included 987 and 903 infants in the single-dose and the extended-dose arms, respectively. HIV transmission was 8.9% in the extended-dose group compared to 10.4% in the single-dose group, but the difference was not significant [risk ratio: 0.87, 95% confidence interval (CI): 0.65-1.15]. Cumulative mortality at 12 months was half in the extended-dose group compared to the single-dose group (risk ratio: 0.53, 95% CI: 0.32-0.85). The impact of extended-dose nevirapine was highest in infants of mothers with CD4 cell count more than 350 cells/μl. Risk ratios for death (risk ratio: 0.38, 95% CI: 0.17-0.84) and HIV transmission or death (risk ratio: 0.54, 95% CI: 0.35-0.85) were statistically significant for the CD4 cell counts more than 350 cells/μl category, whereas none of the risk ratios were significant for the CD4 cell counts 200 cells/μl or less and CD4 cell counts 201-350 cells/μl categories. For populations with limited access to HAART, our results provide evidence for the use of extended-dose regimens to prevent infant deaths and increase HIV-free survival in infants of HIV-infected breastfeeding women, particularly for infants of women with CD4 cell counts more than 350 cells/μl.

Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomised controlled trial

Breastfeeding is essential for child health and development in low-resource settings but carries a significant risk of transmission of HIV-1, especially in late stages of maternal disease. We aimed to assess the efficacy and safety of triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis in pregnant women infected with HIV. Pregnant women with WHO stage 1, 2, or 3 HIV-1 infection who had CD4 cell counts of 200-500 cells per μL were enrolled at five study sites in Burkina Faso, Kenya, and South Africa to start study treatment at 28-36 weeks' gestation. Women were randomly assigned (1:1) by a computer generated random sequence to either triple antiretroviral prophylaxis (a combination of 300 mg zidovudine, 150 mg lamivudine, and 400 mg lopinavir plus 100 mg ritonavir twice daily until cessation of breastfeeding to a maximum of 6·5 months post partum) or zidovudine and single-dose nevirapine (300 mg zidovudine twice daily until delivery and a dose of 600 mg zidovudine plus 200 mg nevirapine at the onset of labour and, after a protocol amendment in December, 2006, 1 week post-partum zidovudine 300 mg twice daily and lamivudine 150 mg twice daily). All infants received a 0·6 mL dose of nevirapine at birth and, from December, 2006, 4 mg/kg twice daily of zidovudine for 1 week after birth. Patients and investigators were not masked to treatment. The primary endpoints were HIV-free infant survival at 6 weeks and 12 months; HIV-free survival at 12 months in infants who were ever breastfed; AIDS-free survival in mothers at 18 months; and serious adverse events in mothers and babies. Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISRCTN71468401. From June, 2005, to August, 2008, 882 women were enrolled, 824 of whom were randomised and gave birth to 805 singleton or first, liveborn infants. The cumulative rate of HIV transmission at 6 weeks was 3·3% (95% CI 1·9-5·6%) in the triple antiretroviral group compared with 5·0% (3·3-7·7%) in the zidovudine and single-dose nevirapine group, and at 12 months was 5·4% (3·6-8·1%) in the triple antiretroviral group compared with 9·5% (7·0-12·9%) in the zidovudine and single-dose nevirapine group (p=0·029). The cumulative rate of HIV transmission or death at 12 months was 10·2% (95% CI 7·6-13·6%) in the triple antiretroviral group compared with 16·0% (12·7-20·0%) in the zidovudine and single-dose nevirapine group (p=0·017). In infants whose mothers declared they intended to breastfeed, the cumulative rate of HIV transmission at 12 months was 5·6% (95% CI 3·4-8·9%) in the triple antiretroviral group compared with 10·7% (7·6-14·8%) in the zidovudine and single-dose nevirapine group (p=0·02). AIDS-free survival in mothers at 18 months will be reported in a different publication. The incidence of laboratory and clinical serious adverse events in both mothers and their babies was similar between groups. Triple antiretroviral prophylaxis during pregnancy and breastfeeding is safe and reduces the risk of HIV transmission to infants. Revised WHO guidelines now recommend antiretroviral prophylaxis (either to the mother or to the baby) during breastfeeding if the mother is not already receiving antiretroviral treatment for her own health. Agence nationale de recherches sur le sida et les hépatites virales, Department for International Development, European and Developing Countries Clinical Trials Partnership, Thrasher Research Fund, Belgian Directorate General for International Cooperation, Centers for Disease Control and Prevention, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction.

HIV-free survival and morbidity among formula-fed infants in a prevention of mother-to-child transmission of HIV program in rural Haiti

BackgroundPartners In Health (PIH) works with the Ministry of Health to provide comprehensive health services in Haiti. Between 1994 and 2009, PIH recommended exclusive formula feeding in the prevention of mother-to-child transmission (PMTCT) of HIV program and provided support to implement this strategy. We conducted this study to assess HIV-free survival and prevalence of diarrhea and malnutrition among infants in our PMTCT program in rural Haiti where exclusive formula feeding was supported.MethodsWe reviewed medical charts of PMTCT mother-infant pairs at PIH between November 2004 and August 2006 through a retrospective longitudinal study and cross-sectional survey. We performed household surveys for each pair and at control households matched by infant's age and gender.Results254 mother-infant pairs were included. 15.3% of infants were low birth weight; most births occurred at home (68.8%). 55.9% of households had no latrine; food insecurity was high (mean score of 18; scale 0-27, SD = 5.3). HIV-free survival at 18 months was 90.6%. Within the cohort, 9 children (3.5%) were HIV-infected and 17 (6.7%) died. Community controls were more likely to be breastfed (P = 0.003) and more likely to introduce food early (P = 0.003) than PMTCT-program households. There was no difference in moderate malnutrition (Z score ≤ 2 SD) between PMTCT and community groups after controlling for guardian's education, marital status, and food insecurity (OR = 1.05; 95% CI: 0.67, 1.64; P = 0.84). Diarrhea was 2.9 times more prevalent among community children than PMTCT infants (30.3% vs. 12.2%; P < 0.0001).ConclusionsIn a PIH-supported program in rural Haiti that addressed socioeconomic barriers to ill-health, breast milk substitution was safe, acceptable and feasible for PMTCT for HIV-infected women choosing this option.

Male Antenatal Attendance and HIV Testing Are Associated With Decreased Infant HIV Infection and Increased HIV-Free Survival

To investigate the relationship between male involvement in prevention of mother-to-child HIV transmission services and infant HIV acquisition and mortality, a prospective cohort study was undertaken between 1999 and 2005 in Nairobi, Kenya. HIV-infected pregnant women were enrolled and followed with their infants for 1 year with infant HIV DNA testing at birth, 1, 3, 6, 9, and 12 months postpartum. Women were encouraged to invite male partners for prevention counseling and HIV testing. Among 456 female participants, 140 partners (31%) attended the antenatal clinic. Eighty-two (19%) of 441 infants tested were HIV infected by 1 year of age. Adjusting for maternal viral load, vertical transmission risk was lower among women with partner attendance compared with those without [adjusted hazard ratio (aHR) = 0.56, 95% confidence interval (CI): 0.33 to 0.98; P = 0.042] and among women reporting versus not reporting previous partner HIV testing (aHR = 0.52, 95% CI: 0.32 to 0.84; P = 0.008). The combined risk of HIV acquisition or infant mortality was lower with male attendance (aHR = 0.55; 95% CI: 0.35 to 0.88; P = 0.012) and report of prior male HIV testing (aHR = 0.58; 95% CI: 0.34 to 0.88; P = 0.01) when adjusting for maternal viral load and breastfeeding. Including men in antenatal prevention of mother-to-child HIV transmission services with HIV testing may improve infant health outcomes.