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Introduction Findings from biomedical, behavioural and implementation studies provide a rich foundation to guide programmatic efforts for the prevention of mother‐to‐child HIV transmission (PMTCT). Methods We summarized the current evidence base to support policy makers, programme managers, funding agencies and other stakeholders in designing and optimizing PMTCT programmes. We searched the scientific literature for PMTCT interventions in the era of universal antiretroviral therapy for pregnant and breastfeeding women (i.e. 2013 onward). Where evidence was sparse, relevant studies from the general HIV treatment literature or from prior eras of PMTCT programme implementation were also considered. Studies were organized into six categories: HIV prevention services for women, timely access to HIV testing, timely access to ART, programme retention and adherence support, timely engagement in antenatal care and services for infants at highest risk of HIV acquisition. These were mapped to specific missed opportunities identified by the UNAIDS Spectrum model and embedded in UNICEF operational guidance to optimize PMTCT services. Results and discussion From May to November 2019, we identified numerous promising, evidence‐based strategies that, properly tailored and adopted, could contribute to population reductions in vertical HIV transmission. These spanned the HIV and maternal and child health literature, emphasizing the importance of continued alignment and integration of services. We observed overlap between several intervention domains, suggesting potential for synergies and increased downstream impact. Common themes included integration of facility‐based healthcare; decentralization of health services from facilities to communities; and engagement of partners, peers and lay workers for social support. Approaches to ensure early HIV diagnosis and treatment prior to pregnancy would strengthen care across the maternal lifespan and should be promoted in the context of PMTCT. Conclusions A wide range of effective strategies exist to improve PMTCT access, uptake and retention. Programmes should carefully consider, prioritize and plan those that are most appropriate for the local setting and best address existing gaps in PMTCT health services.

Introduction High maternal HIV incidence contributes substantially to mother‐to‐child HIV transmission (MTCT) in some settings. Since 2006, HIV retesting during the third trimester and breastfeeding has been recommended by the World Health Organization in higher prevalence (≥5%) settings to reduce MTCT. However, many countries lack clarity on when and how often to retest pregnant and postpartum women to optimize resources and service delivery. We reviewed and characterized national guidelines on maternal retesting based on timing and frequency. Methods We identified 52 countries to represent variations in HIV prevalence, geography, and MTCT priority and searched available national MTCT, HIV testing and HIV treatment policies published between 2007 and 2017 for recommendations on retesting during pregnancy, labour/delivery and postpartum. Recommended retesting frequency and timing was extracted. Country HIV prevalence was classified as: very low (<1%), low (1% to 5%), intermediate (>5 to <15%) and high (≥15%). Women with unknown HIV status at delivery/postpartum were included in retesting guidelines. Results and discussion Overall, policies from 49 countries were identified; 51% from 2015 or later and most (n = 25) were from Africa. Four countries were high HIV prevalence, seven intermediate, sixteen low and twenty‐two very low. Most (n = 31) had guidance on universal voluntary opt‐out HIV testing at the first antenatal care (ANC) visit. Beyond the first ANC visit, the majority (78%, n = 38) had guidance on retesting; 22 recommended retesting all women with unknown/negative status, five only if unknown HIV status, three in pregnancy based on risk and eight combining these approaches. Retesting was universally recommended during pregnancy, labour/delivery, and postpartum for all high prevalence settings and four of seven intermediate prevalence settings. Five UNAIDS priority countries for EMTCT with low/very low HIV prevalence, but high/intermediate MTCT, had no guidance on retesting. Conclusions Retesting guidelines for pregnant and postpartum women were ubiquitous in high prevalence countries and defined in some intermediate prevalence countries, but absent in some low HIV prevalence countries with high MTCT. Countries may require additional guidance on how to optimize maternal HIV testing and whether to prioritize retesting efforts or discontinue universal retesting based on HIV incidence. Research is needed to assess country‐level guideline implementation and impact.

Background Context-specific factors influence adherence to antiretroviral therapy (ART) among pregnant women living with HIV. Gaps exist in the understanding of the reasons for the variable outcomes of the prevention of mother-to-child transmission (PMTCT) programme at the health facility level in South Africa. This study examined adherence levels and reasons for non-adherence during pregnancy in a cohort of parturient women enrolled in the PMTCT programme in the Eastern Cape, South Africa. Methods This was a mixed-methods study involving 1709 parturient women in the Eastern Cape, South Africa. We conducted a multi-centre retrospective analysis of the mother-infant pair in the PMTCT electronic database in 2016. Semi-structured interviews of purposively selected parturient women with self-reported poor adherence ( n  = 177) were conducted to gain understanding of the main barriers to adherence. Binary logistic regression was used to determine the independent predictors of ART non-adherence. Results A high proportion (69.0%) of women reported perfect adherence. In the logistic regression analysis, after adjusting for confounding factors, marital status, cigarette smoking, alcohol use and non-disclosure to a family member were the independent predictors of non-adherence. Analysis of the qualitative data revealed that drug-related side-effects, being away from home, forgetfulness, non-disclosure, stigma and work-related demand were among the main reasons for non-adherence to ART. Conclusions Non-adherence to the antiretroviral therapy among pregnant women in this setting is associated with lifestyle behaviours, HIV-related stigma and ART side-effects. In order to eliminate mother-to-child transmission of HIV, clinicians need to screen for these factors at every antenatal clinic visit.

Introduction: To systematically review the literature on mother‐to‐child transmission in breastfed infants whose mothers received antiretroviral therapy and support the process of updating the World Health Organization infant feeding guidelines in the context of HIV and ART. Methods: We reviewed experimental and observational studies; exposure was maternal HIV antiretroviral therapy (and duration) and infant feeding modality; outcomes were overall and postnatal HIV transmission rates in the infant at 6, 9, 12 and 18 months. English literature from 2005 to 2015 was systematically searched in multiple electronic databases. Papers were analysed by narrative synthesis; data were pooled in random effects meta‐analyses. Postnatal transmission was assessed from four to six weeks of life. Study quality was assessed using a modified Newcastle‐Ottawa Scale (NOS) and GRADE. Results and discussion: Eleven studies were identified, from 1439 citations and review of 72 s. Heterogeneity in study methodology and pooled estimates was considerable. Overall pooled transmission rates at 6 months for breastfed infants with mothers on antiretroviral treatment (ART) was 3.54% (95% CI: 1.15–5.93%) and at 12 months 4.23% (95% CI: 2.97–5.49%). Postnatal transmission rates were 1.08 (95% CI: 0.32–1.85) at six and 2.93 (95% CI: 0.68–5.18) at 12 months. ART was mostly provided for PMTCT only and did not continue beyond six months postpartum. No study provided data on mixed feeding and transmission risk. Conclusions: There is evidence of substantially reduced postnatal HIV transmission risk under the cover of maternal ART. However, transmission risk increased once PMTCT ART stopped at six months, which supports the current World Health Organization recommendations of life‐long ART for all.

Globally, nearly 38 million people are living with HIV, and 1.8 million are children. Each day approximately 5600 people acquire HIV. Since the emerging of HIV, 78 million people have been infected and close to 39 million have died. In developing countries, from all new HIV infections, half are because of mother-to-child transmission (MTCT). The aim of this study is to evaluate the effect of option B+ prevention of mother-to-child HIV transmission (PMTCT) and to develop strategies that contribute to eliminate MTCT in Addis Ababa, Ethiopia. The study was conducted in three hospitals of Addis Ababa, Ethiopia, with a qualitative approach. Sixteen (16) in-depth interviews of HIV-positive mothers who had PMTCT follow-up and six focus group discussions with health professionals who work at a PMTCT unit were conducted. To analyse the data ATLAS.ti version 7 was used. According to the findings of this study mother-to-child HIV transmission was associated with lack of HIV-discordant couples counselling guideline, lack of HIV disclosure strategy and counselling guidelines, unavailability of special PMTCT counselling guideline for HIV-positive commercial sex worker mothers and lack of HIV-free human breast milk (banked human breast milk) for PMTCT. Based on the study findings, a strategy that contributes to eliminate MTCT was developed. Based on the research finding, the following four strategies were developed. Strategy 1: establish and use banked human breast milk for elimination of MTCT; Strategy 2: incorporate obligatory policy for discordant couple testing, counselling and disclosure with option B+ PMTCT; Strategy 3: develop disclosure policy and counselling guideline for PMTCT; and Strategy 4: formulate special PMTCT guideline for HIV-positive commercial sex worker mothers.

Background. We conducted a systematic review of estimates of hepatitis C virus (HCV) vertical transmission risk to update current estimates published more than a decade ago. Methods. PubMed and Embase were searched and 109 articles were included. Pooled estimates of risk were generated for children born to HCV antibody–positive and viremic women, aged ≥18 months, separately by maternal human immunodeficiency virus (HIV) coinfection. Results. Meta-analysis of the risk of vertical HCV infection to children of HCV antibody–positive and RNA-positive women was 5.8% (95% confidence interval [CI], 4.2%–7.8%) for children of HIV-negative women and 10.8% (95% CI, 7.6%–15.2%) for children of HIV-positive women. The adjusted meta-regression model explained 51% of the between-study variation in the 25 included risk estimates. Maternal HIV coinfection was the most important determinant of vertical transmission risk (adjusted odds ratio, 2.56 [95% CI, 1.50–4.43]). Additional methodological (follow-up rate and definition of infection in children) and risk factors independently predicted HCV infection and need to be captured and reported by future studies of vertical transmission. Studies assessing the contribution of nonvertical exposures in early childhood to HCV prevalence among children at risk of vertical transmission are needed. Conclusions. More than 1 in every 20 children delivered by HCV chronically infected women are infected, highlighting that vertical transmission likely constitutes the primary transmission route among children. These updated estimates are a basis for decision making in prioritization of research into risk-reducing measures, and inform case management in clinical settings, especially for HIV-positive women in reproductive age.

Background. Adherence to antiretroviral therapy (ART) is crucial to preventing mother-to-child transmission of human immunodeficiency virus (HIV) and ensuring the long-term effectiveness of ART, yet data are sparse from African routine care programs on maternal adherence to triple ART. Methods. We analyzed data from women who started ART at 13 large health facilities in Malawi between September 2011 and October 2013. We defined adherence as the percentage of days \"covered\" by pharmacy claims. Adherence of ≥90% was deemed adequate. We calculated inverse probability of censoring weights to adjust adherence estimates for informative censoring. We used descriptive statistics, survival analysis, and pooled logistic regression to compare adherence between pregnant and breastfeeding women eligible for ART under Option B+, and nonpregnant and nonbreastfeeding women who started ART with low CD4 cell counts or World Health Organization clinical stage 3/4 disease. Results. Adherence was adequate for 73% of the women during pregnancy, for 66% in the first 3 months post partum, and for about 75% during months 4–21 post partum. About 70% of women who started ART during pregnancy and breastfeeding adhered adequately during the first 2 years of ART, but only about 30% of them had maintained adequate adherence at every visit. Risk factors for inadequate adherence included starting ART with an Option B+ indication, at a younger age, or at a district hospital or health center. Conclusions. One-third of women retained in the Option B+ program adhered inadequately during pregnancy and breastfeeding, especially soon after delivery. Effective interventions to improve adherence among women in this program should be implemented.

Background. The efficacy of preventing perinatal transmission (PT) of human immunodeficiency virus type 1 (HIV-1) depends on both viral load (VL) and treatment duration. The objective of this study was to determine whether initiating highly active antiretroviral therapy (ART) before conception has the potential to eliminate PT. Methods. A total of 8075 HIV-infected mother/infant pairs included from 2000 to 2011 in the national prospective multicenter French Perinatal Cohort (ANRS-EPF) received ART, delivered live-born children with determined HIV infection status, and did not breastfeed. PT was analyzed according to maternal VL at delivery and timing of ART initiation. Results. The overall rate of PT was 0.7% (56 of 8075). No transmission occurred among 2651 infants born to women who were receiving ART before conception, continued ART throughout the pregnancy, and delivered with a plasma VL <50 copies/mL (upper 95% confidence interval [CI], 0.1%). VL and timing of ART initiation were independently associated with PT in logistic regression. Regardless of VL, the PT rate increased from 0.2% (6 of 3505) for women starting ART before conception to 0.4% (3 of 709), 0.9% (24 of 2810), and 2.2% (23 of 1051) for those starting during the first, second, or third trimester (P < .001). Regardless of when ART was initiated, the PT rate was higher for women with VLs of 50–400 copies/mL near delivery than for those with <50 copies/mL (adjusted odds ratio, 4.0; 95% CI, 1.9–8.2). Conclusions. Perinatal HIV-1 transmission is virtually zero in mothers who start ART before conception and maintain suppression of plasma VL.

Introduction The frequency of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in Latin America has decreased considerably. However, new infections continue to be recorded, and the pediatric population remains one of the most vulnerable groups in this region. The main objective of the study was to describe the clinical, epidemiological and psychosocial characteristics of new diagnoses of HIV MTCT in 2018 in the PLANTAIDS network (Paediatric Network for Prevention, Early Detection and Treatment of HIV in Children) during the 3 years following diagnosis. Methodology Retrospective, multicenter, descriptive study based on a 3-year follow-up of patients diagnosed with HIV infection due to MTCT in 2018 in 10 hospitals in 8 Latin American countries (Costa Rica, Ecuador, Mexico, Honduras, El Salvador, Panama, Guatemala and Venezuela). The hospitals belonged to the PLANTAIDS network, which is included in CYTED (Ibero-American Programme of Science and Technology for Development). Results The study population comprised 72 pediatric patients (38.9% male). The median age at diagnosis was 2.4 years (IQR: 0.8–5.4). There were 35 cases of opportunistic infections corresponding to 25 patients (34.7%), with tuberculosis being the most common. Adequate childhood vaccination coverage was achieved in 80.5%. There were 3 cases of acute SARS-CoV-2 infection, and these were asymptomatic or mildly symptomatic. According to the Centers for Disease Control and Prevention (CDC) classification, the most frequent clinical-immunological stage at all check-ups was C1. Three patients died from opportunistic infections and/or advanced HIV infection. Conclusions It is important to diagnose HIV infection early in pediatrics, since early initiation of ART is associated with a decrease in mortality. Despite this, HIV infection has a poor prognosis in children, necessitating adequate follow-up to ensure adherence to health care and ART, although it can sometimes prove difficult in children.

We study threshold regression models that allow the relationship between the outcome and a covariate of interest to change across a threshold value in the covariate. In particular, we focus on continuous threshold models, which experience no jump at the threshold. Continuous threshold regression functions can provide a useful summary of the association between outcome and the covariate of interest, because they offer a balance between flexibility and simplicity. Motivated by collaborative works in studying immune response biomarkers of transmission of infectious diseases, we study estimation of continuous threshold models in this article with particular attention to inference under model misspecification. We derive the limiting distribution of the maximum likelihood estimator, and propose both Wald and test-inversion confidence intervals. We evaluate finite sample performance of our methods, compare them with bootstrap confidence intervals, and provide guidelines for practitioners to choose the most appropriate method in real data analysis. We illustrate the application of our methods with examples from the HIV-1 immune correlates studies.