A 6-Country Collaborative Quality Improvement Initiative to Improve Nutrition and Decrease Mother-to-Child Transmission of HIV in Mother-Infant Pairs.

Despite advances in coverage and quality of prevention of mother-to-child transmission (PMTCT) programs, infant protection from postnatal HIV infection remains an issue in high HIV-burdened countries. We designed a quality improvement (QI) intervention-the Partnership for HIV-Free Survival (PHFS)-to improve infant survival. PHFS convened leaders in 6 sub-Saharan African nations to discover together the best strategies for implementing and scaling up existing PMTCT protocols to ensure optimal health of mother-baby pairs and HIV-free infant survival. We used 3 core technical components-rapid adaptive design, collaborative learning, and scale-up/sustainability designs-to test strategies for accelerating effective PMTCT programming in complex, resource-poor settings. Learning generated included the need for increased ownership and codesign of improvement initiatives with Ministries of Health, better integration of initiatives into existing programs, and the need to sustain QI capability throughout the system. PHFS can serve as a design prototype for future global networks aiming to accelerate improvement, learning, and results.

Outcomes and Cost-Effectiveness of Integrating HIV and Nutrition Service Delivery: Pilots in Malawi and Mozambique.

This paper provides the first estimates of impact and cost-effectiveness for integrated HIV and nutrition service delivery in sub-Saharan Africa. HIV and undernutrition are synergistic co-epidemics impacting millions of children throughout the region. To alleviate this co-epidemic, UNICEF supported small-scale pilot programs in Malawi and Mozambique that integrated HIV and nutrition service delivery. We use trends from integration sites and comparison sites to estimate the number of lives saved, infections averted and/or undernutrition cases cured due to programmatic activities, and to estimate cost-effectiveness. Results suggest that Malawi's program had a cost-effectiveness of $11-29/DALY, while Mozambique's was $16-59/DALY. Some components were more effective than others ($1-4/DALY for Malawi's Male motivators vs. $179/DALY for Mozambique's One stop shops). These results suggest that integrating HIV and nutrition programming leads to a positive impact on health outcomes and should motivate additional work to evaluate impact and determine cost-effectiveness using an appropriate research design.

Early Infant Male Circumcision in Cameroon and Senegal: Demand, Service Provision, and Cultural Context.

BACKGROUND: Male circumcision is almost universal in North and West Africa, and practiced for various reasons. Yet there is little documentation on service delivery, clinical procedures, policies, and programmatic strategies. The United Nations Children's Fund (UNICEF) commissioned country program reviews in 2014 to shed light on the delivery of male circumcision services for infants in Cameroon and Senegal. METHODS: We conducted a policy desk review, key informant interviews, and focus group discussions at health centers and in communities. Between December 2014 and January 2015, we conducted 21 key informant interviews (13 with regional and district officers, 5 with national officers, and 3 with UNICEF officials) and 36 focus group discussions (6 with men, 6 with women, 12 with adolescent boys, and 12 with service providers). Some of the men and women were parents of the adolescents who participated in the focus group discussions. In the French-speaking areas, the focus group discussions were conducted in French through an accredited translator, audio recorded, and transcribed into English. RESULTS: All of the facilities we visited in Cameroon and Senegal offer medical male circumcision, with 10 out of 12 performing early infant male circumcision (EIMC) routinely. Neither country has policies, guidelines, or strategies for EIMC. The procedure is done mainly by untrained service providers, with some providers using modern circumcision devices. There are no key messages on EIMC for families; the increasing demand for EIMC is led by the community. CONCLUSION: Despite the absence of national policies and strategies, EIMC is routinely offered at all levels of the health care system in Cameroon and Senegal, mainly by untrained service providers. Improving circumcision services will require guidelines for EIMC and improvements in training, equipment, supply chains, recordkeeping, and demand creation.

Challenges in infant and young child nutrition in the context of HIV.

There is consensus on the benefits for all infants of exclusive breastfeeding for 6 months and introduction of appropriate complementary foods at 6 months, followed by continued breastfeeding. However, guidelines on infant and young child feeding (IYCF) for HIV-positive mothers have changed continually since 2000. This article explores issues and evidence related to IYCF for the prevention and care of paediatric HIV in resource-limited settings in light of new HIV treatment guidelines, implementation challenges and knowledge gaps.In 2010 the impact of antiretroviral drugs (ARVs) on reducing the risk of mother-to-child transmission of HIV moved WHO to urge countries to endorse either avoidance of all breastfeeding or exclusive breastfeeding for the first 6 months while taking ARVs, depending on which strategy could give their infants the greatest chance of HIV-free survival. Implementation of the 2010 recommendations is challenged by lack of healthcare provider training, weak clinic-community linkages to support mother/infant pairs and lack of national monitoring and reporting on infant feeding indicators.More evidence is needed to inform prevention and treatment of malnutrition among HIV-exposed and HIV-infected children. Knowledge gaps include the effects of prolonged ARV exposure, the cause of HIV-associated growth faltering, the effects of early infant testing on continuation of breastfeeding and specific nutrition interventions needed for HIV-infected children.Significant progress has been made toward keeping mothers alive and reducing paediatric HIV infection, but sustained political, financial and scientific commitment are required to ensure meaningful interventions to eliminate postnatal transmission and meet the nutritional needs of HIV-exposed and HIV-infected children.

Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection.

BACKGROUND: Antiretroviral drugs reduce viral replication and can reduce mother-to-child transmission of HIV either by lowering plasma viral load in pregnant women or through post-exposure prophylaxis in their newborns. In rich countries, highly active antiretroviral therapy (HAART) which usually comprises three drugs, has reduced the mother-to-child transmission rates to around 1-2%, but HAART is not always available in low- and middle-income countries. In these countries, various simpler and less costly antiretroviral regimens have been offered to pregnant women or to their newborn babies, or to both. OBJECTIVES: To determine whether, and to what extent, antiretroviral regimens aimed at decreasing the risk of mother-to-child transmission of HIV infection achieve a clinically useful decrease in transmission risk, and what effect these interventions have on maternal and infant mortality and morbidity. SEARCH STRATEGY: We sought to identify all relevant studies regardless of language or publication status by searching the Cochrane HIV/AIDS Review Group Trials Register, The Cochrane Library, MEDLINE, EMBASE and AIDSearch and relevant conference abstracts. We also contacted research organizations and experts in the field for unpublished and ongoing studies. The original review search strategy was conducted in 2002 and updated in 2006 and again in 2009. SELECTION CRITERIA: Randomised controlled trials of any antiretroviral regimen aimed at decreasing the risk of mother-to-child transmission of HIV infection compared with placebo or no treatment, or compared with another antiretroviral regimen. DATA COLLECTION AND ANALYSIS: Two authors independently selected relevant studies, extracted data and assessed trial quality. For the primary outcomes, we used survival analysis to estimate the probability of infants being infected with HIV (the observed proportion) at various specific time-points and calculated efficacy at a specific time as the relative reduction in the proportion infected. Efficacy, at a specific time, is defined as the preventive fraction in the exposed group compared to the reference group, which is the relative reduction in the proportion infected: 1-(Re/Rf). For those studies where efficacy and hence confidence intervals were not calculated, we calculated the approximate confidence intervals for the efficacy using recommended methods. For analysis of results that are not based on survival analyses we present the relative risk for each trial outcome based on the number randomised. No meta-analysis was conducted as no trial assessed identical drug regimens. MAIN RESULTS: Twenty-five trials including 18,901 participants with a median trial sample size of 627 ranging from 50 to 1,844 participants were included in this update. Twenty-two trials randomised mothers (18 pre-natally and four in labour) and followed up their infants, and three trials randomised infants. The first trial began in April 1991 and assessed zidovudine (ZDV) versus placebo and since then, the type, dosage and duration of drugs to be compared has been modified in each subsequent trial. We present the results stratified by regimen and type of feeding.Antiretrovirals versus placebo In breastfeeding populations, three trials found that:ZDV given to mothers from 36 to 38 weeks gestation, during labour and for 7 days after delivery significantly reduced HIV infection at 4-8 weeks (Efficacy 32.00%; 95% CI 1.50 to 62.50), 3 to 4 months (Efficacy 33.07%; 95% CI 5.57 to 60.57), 6 months (Efficacy 34.55%; 95% CI 9.05 to 60.05), 12 months (Efficacy 34.31%; 95% CI 9.30 to 59.32) and 18 months (Efficacy 29.74%; 95% CI 2.73 to 56.75).ZDV given to mothers from 36 weeks gestation and during labour significantly reduced HIV infection at 4 to 8 weeks (Efficacy 43.78%; 95% CI 8.78 to 78.78) and 3 to 4 months (Efficacy 36.95%; 95% CI 2.94 to 70.96) but not at birth.ZDV plus lamivudine (3TC) given to mothers from 36 weeks gestation, during labour and for 7 days after delivery and to babies for the first 7 days after birth (PETRA 'regimen A') significantly reduced HIV infection (Efficacy 62.75%; 95% CI 40.76 to 84.74) and a combined endpoint of HIV infection or death (Efficacy 62.75 [, ]61.00%; 95% CI 40.76 to 84.74) at 4 to 8 weeks but these effects were not sustained at 18 months.ZDV plus 3TC given to mothers from the start of labour until 7 days after delivery and to babies for the first 7 days after birth (PETRA 'regimen B') significantly reduced HIV infection (Efficacy 41.83%; 95% CI 12.82 to 70.84) and HIV infection or death at 4 to 8 weeks (Efficacy 35.91%; 95% CI 8.41 to 63.41) but the effects were not sustained at 18 months.ZDV plus 3TC given to mothers during labour only (PETRA 'regimen C') with no treatment to babies did not reduce the risk of HIV infection at either 4 to 8 weeks or 18 months.In non-breastfeeding populations, three trials found that:ZDV given to mothers from 14 to 34 weeks gestation and during labour and to babies for the first 6 weeks after birth significantly reduced HIV infection in babies at 18 months (Efficacy 66.22%; 95% CI 33.94 to 98.50).ZDV given to mothers from 36 weeks gestation and during labour with no treatment to babies ('Thai-CDC regimen') significantly reduced HIV infection at 4 to 8 weeks (Efficacy 50.26%; 95% CI 13.80 to 86.72) but not at birthZDV given to mothers from 38 weeks gestation and during labour with no treatment to babies did not influence HIV transmission at 6 months.Longer versus shorter regimens using the same antiretrovirals One trial in a breastfeeding population found that:ZDV given to mothers during labour and to their babies for the first 3 days after birth compared with ZDV given to mothers from 36 weeks and during labour (similar to 'Thai-CDC') resulted in HIV infection rates that were not significantly different at birth, 4-8 weeks, 3 to 4 months, 6 months and 12 months.Three trials in non-breastfeeding populations found that:ZDV given to mothers from 28 weeks gestation during labour and to infants for the first 3 days after birth compared with ZDV given to mothers from 35 weeks gestation through labour and to infants from birth to 6 weeks significantly reduced HIV infection rate at 6 months (Efficacy 45.35 %; 95% CI 1.39 to 89.31) but compared with the same regimen ZDV given to mothers from 28 weeks gestation through labour and to infants from birth to 6 weeks did not result in a statistically significant difference in HIV infection at 6 months. ZDV given to mothers from 35 weeks gestation during labour and to infants for the first 3 days after birth was considered ineffective for reducing transmission rates and this regimen was discontinued.An antenatal/intrapartum course of ZDV used for a median of 76 days compared with an antenatal/intrapartum ZDV regimen used for a median 28 days with no treatment to babies in either group did not result in HIV infection rates that were significantly different at birth and at 3 to 4 months.In a programme where mothers were routinely receiving ZDV in the third trimester of pregnancy and babies were receiving one week of ZDV therapy, a single dose of nevirapine (NVP) given to mothers in labour and to their babies soon after birth compared with a single dose of NVP given to mothers only resulted in HIV infection rates that were not significantly different at birth and 6 months. However the reduction in risk of HIV infection or death at 6 months was marginally significant (Efficacy 45.00%; 95% CI -4.00 to 94.00).Antiretroviral regimens using different drugs and durations of treatmentIn breastfeeding populations, three trials found that:A single dose of NVP given to mothers at the onset of labour plus a single dose of NVP given to their babies immediately after birth ('HIVNET 012 regimen') compared with ZDV given to mothers during labour and to their babies for a week after birth resulted in lower HIV infection rates at 4-8 weeks (Efficacy 41.00%; 95% CI 11.84 to 70.16), 3-4 months (Efficacy 38.91%; 95% CI 11.24 to 66.58), 12 months (Efficacy 35.98 [9.25, 62.71]36.00%; 95% CI 8.56 to 63.44) and 18 months (Efficacy 39.15%; 95% CI 13.81 to 64.49). In addition, the NVP regimen significantly reduced the risk of HIV infection or death at 4-8 weeks (Efficacy 41.74%; 95% CI 14.30 to 69.18), 3 to 4 months (Efficacy 40.00%; 95% CI 14.34 to 65.66), 12 months (Efficacy 32.17%; 95% CI 8.51 to 55.83) and 18 months (Efficacy 32.57 [9.93, 55.21]33.00%; 95% CI 9.93 to 55.21).The 'HIVNET 012 regimen' plus ZDV given to babies for 1 week after birth compared with the 'HIVNET 012 regimen' alone did not result in a statistically significant difference in HIV infection at 4 to 8 weeks.A single dose of NVP given to babies immediately after birth plus ZDV given to babies for 1 week after birth compared with a single dose of NVP given to babies only significantly reduced the HIV infection rate at 4 to 8 weeks (Efficacy 36.79%; 95% CI 3.57 to 70.01).Five trials in non-breastfeeding populations found that:In a population in which mothers were receiving 'standard' antiretroviral for HIV infection a single dose of NVP given to mothers in labour plus a single dose of NVP given to babies immediately after birth ('HIVNET 012 regimen') compared with placebo did not result in a statistically significant difference in HIV infection rates at birth and at 4 to 8 weeks.The 'Thai CDC regimen' compared with the 'HIVNET 012 regimen' did not result in a significant difference in HIV infection at 4 to 8 weeks.A single dose of NVP given to babies immediately after birth compared to ZDV given to babies for the first 6 weeks after birth did not result in a significant difference in HIV infection rates at 4-8 weeks and 3 to 4 months. 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Antiretroviral therapy (ART) for treating HIV infection in ART-eligible pregnant women.

BACKGROUND: This systematic review focuses on antiretroviral therapy (ART) for treating human immunodeficiency virus (HIV) infection in ART-eligible pregnant women. Mother-to-child transmission (MTCT) is the primary means by which children worldwide acquire HIV infection. MTCT occurs during three major timepoints during pregnancy and the postpartum period: in utero, intrapartum, and during breastfeeding. Strategies to reduce MTCT focus on these periods of exposure and include maternal and infant use of ART, caesarean section before onset of labour or rupture of membranes, and complete avoidance of breastfeeding. Where these combined interventions are available, the risk of MTCT is as low as 1-2%. Thus, ART used among mothers who require treatment of HIV for their own health also plays a significant role in decreasing MTCT.This review is one in a series of systematic reviews performed in preparation for the revision of the 2006 World Health Organization (WHO) Guidelines regarding "Antiretroviral Drugs for Treating Pregnant Women and Preventing HIV Infection in Infants" and "Antiretroviral therapy (ART) for HIV Infections in Adults and Adolescents." The findings from these reviews were discussed with experts, key stakeholders, and country representatives at the 2009 WHO guideline review meeting. The resulting WHO 2009 "rapid advice" preliminary guidance on adult and adolescent ART now recommends lifelong treatment for all adults with HIV infection and CD4 counts <350 cells/mm(3). These recommendations also apply to pregnant women who are HIV-infected and they place a high value on early ART to benefit the mother's own health (WHO 2009). The "rapid advice" preliminary guidance also aims to minimize side effects for mothers and their infants (WHO 2009). OBJECTIVES: Our objective was to assess the current literature regarding the treatment of HIV infection in pregnant women who are clinically or immunologically eligible for ART. This review includes an evaluation of the optimal time to start therapy in relation to the woman's laboratory parameters and/or gestational age. It also includes an analysis of which specific antiretroviral medications to start in women who are not yet on ART and which agents to continue in women who are already on ART. SEARCH STRATEGY: In June 2009, electronic searches were undertaken in these databases: Cochrane's "CENTRAL," EMBASE, PubMed, LILACS, and Web of Science/Web of Social Science. Hand searches were performed of the reference lists of all pertinent reviews and studies identified. Abstracts from relevant conferences were searched. Experts in the field were contacted to locate additional studies. The search strategy was iterative. SELECTION CRITERIA: We selected randomized controlled trials and observational studies that evaluated pregnant women with HIV infection who were eligible for ART according to criteria defined by the WHO guideline review committee. Studies were included in the systematic review when a comparison group was clearly defined and where the intervention comprised triple ART. For a study to be considered, each medication in the ART regimen needed to be clearly described. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the selected studies for relevance and inclusion. Relevant data was then extracted from included studies, and the risk of bias assessed. In each included study, the relative risk (RR) for the intervention versus the comparison group was calculated for each outcome, as appropriate, with 95% confidence intervals (CIs). MAIN RESULTS: To our knowledge, there are no randomized controlled trials or observational studies that address the optimal time to start antiretroviral drugs in ART-eligible pregnant women in relation to the woman's laboratory parameters and/or gestational age. The medications to continue in ART-eligible pregnant women who are already receiving ART also have not been evaluated systematically in the current literature. The long-term mortality of HIV-positive pregnant women on ART for their own health, and the long-term virologic or clinical efficacy of ART in treating them, has not been evaluated in randomized clinical trials. In this review, surrogate outcomes for long-term mortality and virologic and clinical efficacy (e.g. MTCT and infant HIV transmission or death) were evaluated to determine the efficacy of specific antiretroviral regimens to start in women who are not yet on ART.Three randomized controlled trials and six observational studies were selected. No studies addressed comparative maternal mortality, which regimens to continue in women already on ART, or the laboratory parameters and gestational age at which to start therapy. The use of zidovudine (AZT), lamivudine (3TC) and lopinavir/ritonavir (LPV-r) starting at 28-36 weeks gestation in a breastfeeding population reduced infant HIV-transmission or death at 12 months compared to a short-course regimen (RR 0.64, 95% CI: 0.44-0.92) (deVincenzi, 2009). Starting AZT, 3TC, and nevirapine (NVP) at 34 weeks in a mixed-feeding population reduced infant HIV-transmission or death at 7 months compared to a short-course regimen (RR 0.39, 95% CI: 0.12-0.85) (Bae, 2008).In the Mma Bana study (a randomized controlled trial in a breastfeeding population) there was no difference in MTCT at six months between the AZT/3TC/LPV-r and AZT, 3TC, and abacavir (ABC) arms (RR 0.17, 95% CI: 0.02-1.44) (Shapiro, 2009). Both regimens also showed 92-95% efficacy in virologic suppression at delivery and during the breastfeeding period. In the Kesho Bora study there was a significant difference in MTCT at 12 months between breastfeeding women who initiated AZT/3TC/LPV-r starting between 28 and 36 weeks and those receiving a short course regimen (RR 0.58, 95% CI: 0.34-0.97) (deVincenzi, 2009). MTCT also decreased significantly when AZT/3TC/NVP was compared with a short-course regimen at seven months in a feeding intervention study (RR 0.15, 95% CI: 0.04-0.62) (Bae, 2008) and 12 months in a population where either exclusive breastfeeding or replacement feeding was encouraged (RR 0.14, CI: 0.04-0.47) (Ekouevi, 2008).In the Mma Bana study, there was increased risk of prematurity among infants born to women receiving AZT/3TC/LPV-r (RR 1.52, CI: 1.07- 2.17) compared with AZT/3TC/ABC (Shapiro, 2009). Ekouevi 2008 showed higher rates of infant low birth weight on AZT/3TC/NVP started at 24 weeks compared to a short course regimen started between 32 and 36 weeks (RR 1.81, 95% CI: 1.09- 3.0). Tonwe-Gold 2007 showed an increase in maternal severe adverse events among the women receiving AZT/3TC/NVP compared with a short-course regimen (RR 25.33, CI 1.49- 340.51). AUTHORS' CONCLUSIONS: In ART-eligible pregnant women with HIV infection, ART is a safe and effective means of providing maternal virologic suppression, decreasing infant mortality, and reducing MTCT. Specifically, AZT/3TC/NVP, AZT/3TC/LPV-r, and AZT/3TC/ABC have been shown to decrease MTCT. More research is needed regarding the use of specific regimens and their maternal and infant side-effect profiles.

Should nevirapine be used to prevent mother-to-child transmission of HIV among women of unknown serostatus?

At present, HIV testing and counselling during pregnancy represent the key entry point for women to learn their serostatus and for them to access, if they are HIV-positive, specific interventions to reduce mother-to-child transmission (MTCT) of HIV. However, the provision and uptake of testing and counselling services are inadequate, and many pregnant women in countries most affected by the HIV/AIDS epidemic remain unaware of their HIV status. The offer of single-dose nevirapine prophylaxis to women whose HIV status is unknown at the time of delivery has been proposed to circumvent these problems in high-prevalence settings. The potential advantages and disadvantages of three different programme approaches are considered: targeted programmes in which antiretroviral drugs are offered only to women who are known to be HIV-positive; combined programmes in which nevirapine prophylaxis is offered to women whose serostatus remains unknown at the time of delivery despite targeted programme inputs; and universal nevirapine prophylaxis programmes in which HIV testing and counselling are not available and all pregnant women, regardless of their serostatus, are offered nevirapine prophylaxis.