Mixed-methods cross-sectional study of the prevention of vertical HIV transmission program users unaware of male partner's HIV status, in six South African districts with a high antenatal HIV burden.

BACKGROUND: Elimination of vertical HIV Transmission (VHT) and maternal deaths are global health priorities. Male involvement is one of the most important factors that influences women's decisions, including the uptake of Prevention of vertical HIV transmission (P-VHT). We sought to understand not knowing a male partner's HIV status (MPHIVs) amongst women using services to prevent vertical HIV transmission in six South African districts with high antenatal HIV burden. METHODS: A mixed-methods cross-sectional study was conducted in six South African districts, and data collected through face-to-face interviews with women and focus group discussions (FGDs) with women or male partners. The quantitative data were analyzed using STATA SE-17.0 and an inductive approach was used for qualitative data analysis. RESULTS: Overall, 28.7% of women were unaware of their MPHIVs, while 25.3% and 46.0% knew the MPHIVs was positive or negative, respectively. In multivariable logistic regression, single marital status and unplanned pregnancy increased the odds of not knowing a MPHIVs while a woman's disclosure of her HIV status to the male partner reduced the odds. FDGs highlighted complexities around MPHIVs disclosure, e.g., reluctance to test for HIV and potential interventions including healthcare worker (HCW) assisted HIV disclosure. CONCLUSION: User-informed interventions to address MPHIVs non-disclosure amongst women of child-bearing age, particularly those at risk of unstable sexual partners and unplanned pregnancies, should be strengthened.

Impact of antenatal antiretroviral drug exposure on the growth of children who are HIV-exposed uninfected: the national South African Prevention of Mother to Child Evaluation cohort study.

BACKGROUND: The relationship between in-utero antiretroviral (ARV) drug exposure and child growth needs further study as current data provide mixed messages. We compared postnatal growth in the first 18-months of life between children who are HIV-exposed uninfected (CHEU) with fetal exposure to ARV drugs (prophylaxis or triple-drug therapy (ART)) and CHEU not exposed to ARVs. We also examined other independent predictors of postnatal growth. METHODS: We analysed data from a national prospective cohort study of 2526 CHEU enrolled at 6-weeks and followed up 3-monthly till 18-months postpartum, between October 2012 and September 2014. Infant anthropometry was measured, and weight-for-age (WAZ) and length-for-age (LAZ) Z-scores calculated. Generalized estimation equation models were used to compare Z-scores between groups. RESULTS: Among 2526 CHEU, 617 (24.4%) were exposed to ART since -pregnancy (pre-conception ART), 782 (31.0%) to ART commencing post-conception, 879 (34.8%) to maternal ARV prophylaxis (Azidothymidine (AZT)), and 248 (9.8%) had no ARV exposure. In unadjusted analyses, preterm birth rates were higher among CHEU with no ARV exposure than in other groups. Adjusting for infant age, the mean WAZ profile was lower among CHEU exposed to pre-conception ART [-0.13 (95% confidence interval - 0.26; - 0.01)] than the referent AZT prophylaxis group; no differences in mean WAZ profiles were observed for the post-conception ART (- 0.05 (- 0.16; 0.07)), None (- 0.05 (- 0.26; 0.16)) and newly-infected (- 0.18 (- 0.48; 0.13)) groups. Mean LAZ profiles were similar across all groups. In multivariable analyses, mean WAZ and LAZ profiles  for the ARV exposure groups were completely aligned. Several non-ARV factors including child, maternal, and socio-demographic factors independently predicted mean WAZ. These include child male (0.45 (0.35; 0.56)) versus female, higher maternal education grade 7-12 (0.28 (0.14; 0.42) and 12 + (0.36 (0.06; 0.66)) versus ≤ grade7, employment (0.16 (0.04; 0.28) versus unemployment, and household food security (0.17 (0.03; 0.31). Similar predictors were observed for mean LAZ. CONCLUSION: Findings provide evidence for initiating all pregnant women living with HIV on ART as fetal exposure had no demonstrable adverse effects on postnatal growth. Several non-HIV-related maternal, child and socio-demographic factors were independently associated with growth, highlighting the need for multi-sectoral interventions. Longer-term monitoring of CHEU children is recommended.

An approach for evaluating early and long term mother-to-child transmission of HIV (MTCT) in low and middle income countries: a South African experience.

BACKGROUND: Eliminating mother-to-child transmission of HIV is a global public health target. Robust, feasible methodologies to measure population level impact of programmes to prevent mother-to-child transmission of HIV (PMTCT) are needed in high HIV prevalence settings. We present a summary of the protocol of the South African PMTCT Evaluation (SAPMTCTE) with its revision over three repeated rounds of the survey, 2010-2014. METHODS: Three cross sectional surveys (2010, 2011-2012 and 2012-2013) were conducted in 580 primary health care immunisation service points randomly selected after stratified multistage probability proportional to size sampling. All infants aged 4-8 weeks receiving their six-week immunisation at a sampled facility on the day of the visit were eligible to participate. Trained research nurses conducted interviews and took infant dried blood spot (iDBS) samples for HIV enzyme immunoassay (EIA) and total nucleic acid polymerase chain reaction (PCR) testing. Interviews were conducted using mobile phones and iDBS were sent to the National Health Laboratory for testing. All findings were adjusted for study design, non-response, and weighted for number of South African live-birth in each study round. In 2012 a national closed cohort of these 4 to 8-week old infants testing EIA positive (HIV Exposed Infants) from the 2012-2013 cross-sectional survey was established to estimate longer-term PMTCT impact to 18 months. Follow-up analyses were to estimate weighted cumulative MTCT until 18 months, postnatal MTCT from 6 weeks until 18 months and a combined outcome of MTCT-or-death, using a competing risks model, with death as a competing risk. HIV-free survival was defined as a child surviving and HIV-negative up to 18 months or last visit seen. A weighted cumulative incidence analysis was conducted, adjusting for survey design effects. DISCUSSION: In the absence of robust high-quality routine medical recording systems, in the context of a generalised HIV epidemic, national surveys can be used to monitor PMTCT effectiveness; however, monitoring long-term outcomes nationally is difficult due to poor retention in care.

What will it take for the Global Plan priority countries in Sub-Saharan Africa to eliminate mother-to-child transmission of HIV?

BACKGROUND: The 2016 'Start Free, Stay Free, AIDS Free' global agenda, builds on the 2011-2015 'Global Plan'. It prioritises 22 countries where 90% of the world's HIV-positive pregnant women live and aims to eliminate vertical  transmission of HIV (EMTCT) and to keep mothers alive. By 2019, no Global Plan priority country had achieved EMTCT; however, 11 non-priority countries had. This paper synthesises the characteristics of the first four countries validated for EMTCT, and of the 21 Global Plan priority countries located in Sub-Saharan Africa (SSA). We consider what drives vertical transmission of HIV (MTCT) in the 21 SSA Global Plan priority countries. METHODS: A literature review, using PubMed, Science direct and the google search engine was conducted to obtain global and national-level information on current HIV-related context and health system characteristics of the first four EMTCT-validated countries and the 21 SSA Global Plan priority countries. Data representing only one clinic, hospital or region were excluded. Additionally, key global experts working on EMTCT were contacted to obtain clarification on published data. We applied three theories (the World Health Organisation's building blocks to strengthen health systems, van Olmen's Health System Dynamics framework and Baral's socio-ecological model for HIV risk) to understand and explain the differences between EMTCT-validated and non-validated countries. Additionally, structural equation modelling (SEM) and linear regression were used to explain associations between infant HIV exposure, access to antiretroviral therapy and two outcomes: (i) percent MTCT and (iii) number of new paediatric HIV infections per 100 000 live births (paediatric HIV case rate). RESULTS: EMTCT-validated countries have lower HIV prevalence, less breastfeeding, fewer challenges around leadership, governance within the health sector or country, infrastructure and service delivery compared with Global Plan priority countries. Although by 2016 EMTCT-validated countries and Global Plan priority countries had adopted a public health approach to HIV prevention, recommending lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and lactating women, EMCT-validated countries had also included contact tracing such as assisted partner notification, and had integrated maternal and child health (MCH) and sexual and reproductive health (SRH) services, with services for HIV infection, sexually transmitted infections, and viral hepatitis. Additionally, Global Plan priority countries have limited data on key SRH indicators such as unmet need for family planning, with variable coverage of antenatal care, HIV testing and triple antiretroviral therapy (ART) and very limited contact tracing. Structural equation modelling (SEM) and linear regression analysis demonstrated that ART access protects against percent MTCT (p<0.001); in simple linear regression it is 53% protective against percent MTCT. In contrast, SEM demonstrated that the case rate was driven by the number of HIV exposed infants (HEI) i.e. maternal HIV prevalence (p<0.001). In linear regression models, ART access alone explains only 17% of the case rate while HEI alone explains 81% of the case rate. In multiple regression, HEI and ART access accounts for 83% of the case rate, with HEI making the most contribution (coef. infant HIV exposure=82.8, 95% CI: 64.6, 101.1, p<0.001 vs coef. ART access=-3.0, 95% CI: -6.2, 0.3, p=0.074). CONCLUSION: Reducing infant HIV exposure, is critical to reducing the paediatric HIV case rate; increasing ART access is critical to reduce percent MTCT. Additionally, our study of four validated countries underscores the importance of contact tracing, strengthening programme monitoring, leadership and governance, as these are potentially-modifiable factors.

HIV infection, viral load, low birth weight, and nevirapine are independent influences on growth velocity in HIV-exposed South African infants.

Data from a prospective multisite cohort study were used to examine the effect of HIV exposure, untreated HIV infection, and single-dose nevirapine on infant growth velocity. The 2009 WHO growth velocity standards constitute a new tool for this type of investigation and are in need of functional validation. In period 1 (3-24 wk), 65 HIV-infected, 502 HIV-exposed uninfected (HEU), and 216 HIV-unexposed infants were included. In period 2 (25-36 wk), 31 infants moved from the HEU group to the HIV-infected group. We compared weight velocity Z-scores (WVZ) and length velocity Z-scores (LVZ) by HIV group and assessed their independent influences. In period 1, mean WVZ (95% CI) was significantly (P < 0.001) lower in infected [-0.87 (-1.77, 0.04)] than HEU [0.81 (0.67, 0.94)] and unexposed [0.55 (0.33, 0.78)] infants. LVZ showed similar associations. In both periods, sick infants and those exposed to higher maternal viral loads had lower WVZ. Higher mean LVZ was associated with low birth weight. Infants that had received nevirapine had higher LVZ. In conclusion, HIV infection and not exposure was associated with low WVZ and LVZ in period 1. Eliminating infant HIV infection is a critical component in averting HIV-related poor growth patterns in infants in the first 6 mo of life.

Global challenges with scale-up of the integrated management of childhood illness strategy: results of a multi-country survey.

BACKGROUND: The Integrated Management of Childhood Illness Strategy (IMCI), developed by WHO/UNICEF, aims to contribute to reducing childhood morbidity and mortality (MDG4) in resource-limited settings. Since 1996 more than 100 countries have adopted IMCI. IMCI case management training (ICMT) is one of three IMCI components and training is usually residential over 11 consecutive days. Follow-up after ICMT is an essential part of training. We describe the barriers to rapid acceleration of ICMT and review country perspectives on how to address these barriers. METHODS: A multi-country exploratory cross-sectional questionnaire survey of in-service ICMT approaches, using quantitative and qualitative methods, was conducted in 2006-7: 27 countries were purposively selected from all six WHO regions. Data for this paper are from three questionnaires (QA, QB and QC), distributed to selected national focal IMCI persons/programme officers, course directors/facilitators and IMCI trainees respectively. QC only gathered data on experiences with IMCI follow-up. RESULTS: 33 QA, 163 QB and 272 QC were received. The commonest challenges to ICMT scale-up relate to funding (high cost and long duration of the residential ICMT), poor literacy of health workers, differing opinions about the role of IMCI in improving child health, lack of political support, frequent changes in staff or rules at Ministries of Health and lack of skilled facilitators. Countries addressed these challenges in several ways including increased advocacy, developing strategic linkages with other priorities, intensifying pre-service training, re-distribution of funds and shortening course duration. The commonest challenges to follow-up after ICMT were lack of funding (93.1% of respondents), inadequate funds for travelling or planning (75.9% and 44.8% respectively), lack of gas for travelling (41.4%), inadequately trained or few supervisors (41.4%) and inadequate job aids for follow-up (27.6%). Countries addressed these by piggy backing IMCI follow-up with routine supervisory visits. CONCLUSIONS: Financial challenges to ICMT scale-up and follow-up after training are common. As IMCI is accepted globally as one of the key strategies to meet MDG4 several steps need to be taken to facilitate rapid acceleration of ICMT, including reviewing core competencies followed by competency-driven shortened training duration or 'on the job' training, 'distance learning' or training using mobile phones. Linkages with other 'better-funded' programmes e.g. HIV or malaria need to be improved. Routine Primary Health Care (PHC) supervision needs to include follow-up after ICMT.

Results of a multi-country exploratory survey of approaches and methods for IMCI case management training.

BACKGROUND: The Integrated Management of Childhood Illness Strategy (IMCI) is effective in improving management of sick children, and thus child survival. It is currently recommended that in-service IMCI case management training (ICMT) occur over 11-days; that the participant: facilitator ratio should be

An Early Infant HIV Risk Score for Targeted HIV Testing at Birth.

BACKGROUND: Early HIV testing is needed for treatment success in young infants, but universal testing is expensive. In this study, we examined the feasibility of early infant HIV risk scores for targeted polymerase chain reaction (PCR) testing and early HIV diagnosis. METHODS: A cross-sectional cohort of newborns exposed to HIV was enrolled and PCR tested within 72 hours. We quantified associations between HIV infection and clinical and laboratory maternal-infant parameters by logistic regression models and determined sensitivity and specificity for derived risk scores. RESULTS: From August 2014 to December 2016, 1759 participants were enrolled. Mothers without antenatal care (5.7% [97 of 1688]) were more likely to deliver newborns who are PCR-positive (P = .0005). A total of 1 in 5 mothers (217 of 990; 21.9%) had HIV viral load (VL) >1000 copies per µL. A total of 432 of 1655 (26.1%) infants were preterm. Low birth weight was documented in 398 of 1598 (24.55%) and 13 of 31 (40.63%) newborns who are PCR-negative and -positive, respectively (P = .0329). A total of 204 of 1689 (12.08%) were growth restricted or small for gestational age, and 6 of 37 (16.22%) were PCR-positive. Symptomatic newborns frequently tested positive (P = .0042). The HIV PCR positivity rate was 2.2% (37 of 1703). Two-risk (combined 3-drug antiretroviral therapy [cART] duration, VL), 3-risk (cART duration, VL, symptomatic newborn), and 4-risk (cART duration, VL, symptomatic, small for gestational age newborn) models for HIV acquisition had predictive probability of 0.28, 0.498, and 0.57, respectively; this could guide targeted birth testing. However, using the 3- and 4-risk scores (probability 0.02 and 0.04), 20% and 24% will be missed compared with universal testing. CONCLUSIONS: Targeted newborn testing requires access to maternal VL. Even if risk models include parameters such as maternal cART history, birth weight, weeks' gestation, and symptoms, 1 in 5 newborns who are infected will not be targeted. At present, we support universal PCR testing at birth within the South African prevention of mother-to-child transmission of HIV context.

Transmission of CMV, HTLV-1, and HIV through breastmilk.

Breastfeeding is a crucial child survival intervention. However, the potential for transmission of viral infections from mother to child presents the dilemma of how best to interpret the benefits and risks of breastfeeding in different settings. In this Review, we compare the transmission dynamics, risk factors, and outcomes of infection with three chronic viruses transmitted through breastmilk: cytomegalovirus, human T-cell lymphotropic virus type 1, and HIV. We provide an overview of intervention approaches and discuss scientific, policy, and programming gaps in the understanding of these major global infections.

Non-nucleoside reverse transcriptase inhibitor levels among HIV-exposed uninfected infants at the time of HIV PCR testing - findings from a tertiary healthcare facility in Pretoria, South Africa.

INTRODUCTION: To date, very little programmatic data has been published regarding serial antiretroviral (ARV) levels in infants exposed to maternal treatment and/or infant prophylaxis during the first months of life. Such data provide the opportunity to describe the proportion of infants exposed to virologically suppressive levels of ARVs and to gauge adherence to the prevention of mother-to-child transmission of HIV (PMTCT) programme. METHODS: From August 2014 to January 2016, HIV-exposed infants born at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa were enrolled as part of an observational cohort study. Plasma samples from HIV-exposed uninfected infants were obtained at birth, 6-weeks, 10-weeks and 14-weeks of age and quantitative efavirenz (EFV) and nevirapine (NVP) drug level testing performed using liquid chromatography-mass spectrometry, irrespective of maternal ARV regimen. Descriptive analysis of EFV and NVP levels in relation to self-reported maternal and infant ARV exposure was performed. EFV levels >500 ng/mL and NVP levels >100 ng/mL were reported based on studies suggesting that trough levels above these thresholds are associated with virological suppression and PMTCT respectively. RESULTS: Among 66 infants exposed to maternal EFVin utero, 29 (44%) had virologically suppressive plasma EFV levels at birth, with a median level of 1665 ng/mL (IQR: 1094 to 3673). Among infants who were exclusively breastfed at 6-, 10- and 14 weeks, 13/48 (27%), 5/25 (25%) and 0/21 (0%) had virologically suppressive EFV levels. Among 64 infants whose mothers reported administering daily infant NVP at time of their 6-week HIV PCR test, only 45 (70%) had NVP levels above the minimum prophylactic trough level. CONCLUSIONS: During the first 10-weeks after delivery, a quarter of breastfed infants born to women on an EFV-containing treatment regimen maintained virologically suppressive EFV plasma levels. This finding highlights the importance of both careful monitoring of ARV side effects and repeat HIV PCR after the first few months of life among HIV-exposed uninfected infants. As 30% of infants had inadequate NVP plasma levels at 6-weeks of age, adherence counselling to caregivers regarding infant prophylaxis needs to be enhanced to further reduce mother-to-child transmission of HIV.

The effectiveness and cost-effectiveness of community-based support for adolescents receiving antiretroviral treatment: an operational research study in South Africa.

INTRODUCTION: Adolescents and youth receiving antiretroviral treatment (ART) in sub-Saharan Africa have high attrition and inadequate ART outcomes, and evaluations of interventions improving ART outcomes amongst adolescents are very limited. Sustainable Development Goal (SDG) target 3c is to substantially increase the health workforce in developing countries. We measured the effectiveness and cost-effectiveness of community-based support (CBS) provided by lay health workers for adolescents and youth receiving ART in South Africa. METHODS: A retrospective cohort study including adolescents and youth who initiated ART at 47 facilities. Previously unemployed CBS-workers provided home-based ART-related education, psychosocial support, symptom screening for opportunistic infections and support to access government grants. Outcomes were compared between participants who received CBS plus standard clinic-based care versus participants who received standard care only. Cumulative incidences of all-cause mortality and loss to follow-up (LTFU), adherence measured using medication possession ratios (MPRs), CD4 count slope, and virological suppression were analysed using multivariable Cox, competing-risks regression, generalized estimating equations and mixed-effects models over five years of ART. An expenditure approach was used to determine the incremental cost of CBS to usual care from a provider perspective. Incremental cost-effectiveness ratios were calculated as annual cost per patient-loss (through death or LTFU) averted. RESULTS: Amongst 6706 participants included, 2100 (31.3%) received CBS. Participants who received CBS had reduced mortality, adjusted hazard ratio (aHR) = 0.52 (95% CI: 0.37 to 0.73; p < 0.0001). Cumulative LTFU was 40% lower amongst participants receiving CBS (29.9%) compared to participants without CBS (38.9%), aHR = 0.60 (95% CI: 0.51 to 0.71); p < 0.0001). The effectiveness of CBS in reducing attrition ranged from 42.2% after one year to 35.9% after five years. Virological suppression was similar after three years, but after five years 18.8% CBS participants versus 37.2% non-CBS participants failed to achieve viral suppression, adjusted odds ratio = 0.24 (95% CI: 0.06 to 1.03). There were no significant differences in MPR or CD4 slope. The cost of CBS was US$49.5/patient/year. The incremental cost per patient-loss averted was US$600 and US$776 after one and two years, respectively. CONCLUSIONS: CBS for adolescents and youth receiving ART was associated with substantially reduced patient attrition, and is a low-cost intervention with reasonable cost-effectiveness that can aid progress towards several health, economic and equality-related SDG targets.

Completeness of patient-held records: observations of the Road-to-Health Booklet from two national facility-based surveys at 6 weeks postpartum, South Africa.

BACKGROUND: Continuity of care is important for child well-being in all settings where postnatal retention of mother-infant pairs in care remains a challenge. This analysis reports on completeness of patient-held infant Road to Health Booklets (RtHBs), amongst HIV exposed and unexposed infants during the first two years after the RtHB was launched country-wide in South Africa. METHODS: Secondary data were analysed from two nationally representative, cross-sectional surveys, conducted in 2011-12 and 2012-13. These surveys aimed to measure early effectiveness of the national programme for preventing vertical HIV transmission. Participants were eligible for this analysis if they were 4-8 weeks old, receiving their six-week immunisation, not needing emergency care and had their RtHBs reviewed. Caregivers were interviewed and data abstracted from RtHBs. RtHB completeness across both surveys was defined as the proportion of RtHBs with any of the following indicators recorded: infant birth weight, BCG immunisation, maternal syphilis results and maternal HIV status. A partial proportional odds logistic regression model was used to identify factors associated with completeness. Survey sampling weights were included in all analyses. RESULTS: Data from 10 415 (99.6%) participants in 2011-12 and 9529 (99.2%) in 2012-13 were analysed. Overall, recording of all four indicators increased from 23.1% (95% confidence interval (CI) = 22.2-24.0) in 2011-12 to 43.3% (95% CI = 42.3-44.4) in 2012-13. In multivariable models, expected RtHB completeness (ie, recording all four indicators vs recording of <4 indicators), was significantly (P<0.05) associated with survey year, marital status, socio-economic status, maternal antenatal TB screening, antenatal infant feeding counselling, delivery at a clinic or hospital and type of birth attendant. CONCLUSIONS: Routine patient-held infant health RtHB, a critical tool for continuity of care in high HIV/TB prevalence settings, was poorly completed, with less than 50% of the RtHB showing expected completeness. However, government efforts for improved usage of the booklet were evidenced by the near doubling of completeness from 2011 to 2013. Education about its importance and interventions aiming at optimising its use without violating user privacy should be continued.

Adolescent Access to Care and Risk of Early Mother-to-Child HIV Transmission.

PURPOSE: Adolescent females aged 15-19 account for 62% of new HIV infections and give birth to 16 million infants annually. We quantify the risk of early mother-to-child transmission (MTCT) of HIV among adolescents enrolled in nationally representative MTCT surveillance studies in South Africa. METHODS: Data from 4,814 adolescent (≤19 years) and 25,453 adult (≥20 years) mothers and their infants aged 4-8 weeks were analyzed. These data were gathered during three nationally representative, cross-sectional, facility-based surveys, conducted in 2010, 2011-2012, and 2012-2013. All infants were tested for HIV antibody (enzyme immunoassay), to determine HIV exposure. Enzyme immunoassay-positive infants or those born to self-reported HIV-positive mothers were tested for HIV infection (total nucleic acid polymerase chain reaction). Maternal HIV positivity was inferred from infant HIV antibody positivity. All analyses were weighted for sample realization and population live births. RESULTS: Adolescent mothers, compared with adult mothers, have almost three times less planned pregnancies 14.4% (95% confidence interval [CI]: 12.5-16.5) versus 43.9% (95% CI: 42.0-45.9) in 2010 and 15.2% (95% CI: 13.0-17.9) versus 42.8% (95% CI: 40.9-44.6) in 2012-2013 (p < .0001), less prevention of MTCT uptake (odds ratio [OR] in favor of adult mothers = 3.36, 95% CI: 2.95-3.83), and higher early MTCT (adjusted OR = 3.0, 95% CI: 1.1-8.0), respectively. Gestational age at first antenatal care booking was the only significant predictor of early MTCT among adolescents. CONCLUSIONS: Interventions that appeal to adolescents and initiate sexual and reproductive health care early should be tested in low- and middle-income settings to reduce differential service uptake and infant outcomes between adolescent and adult mothers.

Operational effectiveness and 36 week HIV-free survival in the South African programme to prevent mother-to-child transmission of HIV-1.

OBJECTIVE: Previous studies on the operational effectiveness of programmes to reduce transmission of HIV from mother-to-child (PMTCT) in Africa have generally been hospital-based pilot studies with short follow-up periods. METHOD: Prospective cohort study to evaluate the routine operational effectiveness of the South African National PMTCT Programme, primarily measured by HIV-free survival at 36 weeks post-delivery. Three of eighteen pilot sites participating in the programme were selected as they reflected differences in circumstances, such as HIV prevalence, socioeconomic status and rural-urban location. A total of 665 HIV-positive mothers and their infants were followed. RESULTS: HIV-free survival at 36 weeks varied significantly across sites with 84% in Paarl, 74% in Umlazi and 65% in Rietvlei (P = 0.0003). Maternal viral load was the single most important factor associated with HIV transmission or death [hazard ratio (HR), 1.54; 95% confidence interval (CI), 1.21-1.95]. Adjusting for health system variables (fewer than four antenatal visits and no antenatal syphilis test) explained the difference between Rietvlei and Paarl (crude HR, 2.27; 95% CI, 1.36-3.77; adjusted HR, 1.81; 95% CI, 0.93-3.50). Exposure to breastmilk feeding explained the difference between Umlazi and Paarl (crude HR, 1.74; 95% CI, 1.06-2.84; adjusted HR, 1.41; 95% CI, 0.81-2.48). CONCLUSION: Ever breastfeeding and underlying inequities in healthcare quality within South Africa are predictors of PMTCT programme performance and will need to be addressed to optimize PMTCT effectiveness.

In Utero ART Exposure and Birth and Early Growth Outcomes Among HIV-Exposed Uninfected Infants Attending Immunization Services: Results From National PMTCT Surveillance, South Africa.

BACKGROUND: Despite the recognized benefit of antiretroviral therapy (ART) for preventing and treating HIV, some studies have reported adverse birth outcomes with in utero ART exposure. We evaluated the effect of infant in utero HIV and ART exposure on preterm delivery (PTD), low birth weight (LBW), small for gestational age (SGA), and underweight for age (UFA) at 6 weeks. METHODS: We surveyed 6179 HIV-unexposed-uninfected (HUU) and 2599 HIV-exposed-uninfected (HEU) infants. HEU infants were stratified into 3 groups: ART, Zidovudine alone, and no antiretrovirals (None). The ART group was further stratified to explore pre- or postconception exposure. Multivariable logistic regression evaluated effects of HIV and ARV exposure on the outcomes. RESULTS: We found higher odds of PTD, LBW, SGA, and UFA in HEU than HUU infants. HEU in the None group (adjusted odds ratio [AOR], 1.9; 95% confidence interval [CI], 1.2-3.0) or those whose mothers initiated ART preconception (AOR, 1.7; 95% CI, 1.1-2.5) had almost twice the odds of PTD than infants whose mothers started ART postconception, but no increased odds for other outcomes. CONCLUSIONS: There was an association between preconception ART and PTD. As ART access increases, pregnancy registers or similar surveillance should be in place to monitor outcomes to inform future policy.

Using the PMTCT Cascade to Accelerate Achievement of the Global Plan Goals.

BACKGROUND: Development of country plans for prevention of mother-to-child HIV transmission (PMTCT), including expansion of comprehensive, integrated services, was key to Global Plan achievements. APPROACHES: Use of the PMTCT cascade, an evolving series of sequential steps needed to maximize the health of women and HIV-free survival of infants, was critical for development and implementation of PMTCT plans. Regular review of cascade data at national/subnational levels was a tool for evidence-based decision making, identifying areas of greatest need at each level, and targeting program interventions to address specific gaps. Resulting improvements in PMTCT service delivery contributed to success. Populating the cascade highlighted limitations in data availability and quality that focused attention on improving national health information systems. LIMITATIONS: Use of aggregate, cross-sectional data in the PMTCT cascade presents challenges in settings with high mobility and weak systems to track women and children across services. Poor postnatal follow-up and losses at each step of the cascade have limited use of the cascade approach to measure maternal and child health outcomes beyond the early postnatal period. LESSONS LEARNED: A cascade approach was an effective means for countries to measure progress, identify suboptimal performance areas, and be held accountable for progress toward achievement of Global Plan goals. Using the cascade requires investment of time and effort to identify the type, source, and quality of data needed as programs evolve. Ongoing review of cascade data, with interventions to address discontinuities in the continuum of care, can translate across health areas to improve health care quality and outcomes.

Structural Level Differences in the Mother-to-Child HIV Transmission Rate in South Africa: A Multilevel Assessment of Individual-, Health Facility-, and Provincial-Level Predictors of Infant HIV Transmission.

OBJECTIVES: In 2010, South Africa reported an early mother-to-child transmission (MTCT) rate of 3.5% at 4-8 weeks postpartum. Provincial early MTCT rates ranged from 1.4% [95% confidence interval (CI): 0.1 to 3.4] to 5.9% (95% CI: 3.8 to 8.0). We sought to determine reasons for these geographic differences in MTCT rates. METHODS: This study used multilevel modeling using 2010 South African prevention of mother-to-child transmission (PMTCT) evaluation (SAPMTCTE) data from 530 facilities. Interview data and blood samples of infants were collected from 3085 mother-infant pairs at 4-8 weeks postpartum. Facility-level data on human resources, referral systems, linkages to care, and record keeping were collected through facility staff interviews. Provincial level data were gathered from publicly available data (eg, health professionals per 10,000 population) or aggregated at province-level from the SAPMTCTE (PMTCT maternal-infant antiretroviral (ARV) coverage). Variance partition coefficients and odds ratios (for provincial facility- and individual-level factors influencing MTCT) from multilevel modeling are reported. RESULTS: The provincial- (5.0%) and facility-level (1.4%) variance partition coefficients showed no substantive geographic variation in early MTCT. In multivariable analysis accounting for the multilevel nature of the data, the following were associated with early MTCT: individual-level-low maternal-infant ARV uptake [adjusted odds ratio (AOR) = 2.5, 95% CI: 1.7 to 3.5], mixed breastfeeding (AOR = 1.9, 95% CI: 1.3 to 2.9) and maternal age <20 years (AOR 1.8, 95% CI: 1.1 to 3.0); facility-level-insufficient (≤2) health care-personnel for HIV-testing services (AOR = 1.8, 95% CI: 1.1 to 3.0); provincial-level PMTCT ARV (maternal-infant) coverage lower than 80% (AOR = 1.4, 95% CI: 1.1 to 1.9), and number of health professionals per 10,000 population (AOR = 0.99, 95% CI: 0.98 to 0.99). CONCLUSIONS: There was no substantial province-/facility-level MTCT difference. This could be due to good overall performance in reducing early MTCT. Disparities in human resource allocation (including allocation of insufficient health care personnel for testing and care at facility level) and PMTCT coverage influenced overall PMTCT programme performance. These are long-standing systemic problems that impact quality of care.

Correction to: Effects of early feeding on growth velocity and overweight/obesity in a cohort of HIV unexposed South African infants and children.

[This corrects the article DOI: 10.1186/s13006-015-0041-x.].

Population-level effectiveness of PMTCT Option A on early mother-to-child (MTCT) transmission of HIV in South Africa: implications for eliminating MTCT.

BACKGROUND: Eliminating mother-to-child transmission of HIV (EMTCT), defined as ≤50 infant HIV infections per 100 000 live births, is a global priority. Since 2011 policies to prevent mother-to-child transmission of HIV (PMTCT) shifted from maternal antiretroviral (ARV) treatment or prophylaxis contingent on CD4 cell count to lifelong maternal ARV treatment (cART). We sought to measure progress with early (4-8 weeks postpartum) MTCT prevention and elimination, 2011-2013, at national and sub-national levels in South Africa, a high antenatal HIV prevalence setting ( ≈ 29%), where early MTCT was 3.5% in 2010. METHODS: Two surveys were conducted (August 2011-March 2012 and October 2012-May 2013), in 580 health facilities, randomly selected after two-stage probability proportional to size sampling of facilities (the primary sampling unit), to provide valid national and sub-national-(provincial)-level estimates. Data collectors interviewed caregivers of eligible infants, reviewed patient-held charts, and collected infant dried blood spots (iDBS). Confirmed positive HIV enzyme immunoassay (EIA) and positive total HIV nucleic acid polymerase chain reaction (PCR) indicated infant HIV exposure or infection, respectively. Weighted survey analysis was conducted for each survey and for the pooled data. FINDINGS: National data from 10 106 and 9120 participants were analyzed (2011-12 and 2012-13 surveys respectively). Infant HIV exposure was 32.2% (95% confidence interval (CI) 30.7-33.6%), in 2011-12 and 33.1% (95% CI 31.8-34.4%), provincial range of 22.1-43.6% in 2012-13. MTCT was 2.7% (95% CI 2.1%-3.2%) in 2011-12 and 2.6% (95% CI 2.0-3.2%), provincial range of 1.9-5.4% in 2012-13. HIV-infected ARV-exposed mothers had significantly lower unadjusted early MTCT (2.0% [2011-12: 1.6-2.5%; 2012-13:1.5-2.6%]) compared to HIV-infected ARV-naive mothers [10.2% in 2011-12 (6.5-13.8%); 9.2% in 2012-13 (5.6-12.7%)]. Pooled analyses demonstrated significantly lower early MTCT among exclusive breastfeeding (EBF) mothers receiving >10 weeks ARV prophylaxis or cART compared with EBF and no ARVs: (2.2% [95% CI 1.25-3.09%] vs 12.2% [95% CI 4.7-19.6%], respectively); among HIV-infected ARV-exposed mothers, 24.9% (95% CI 23.5-26.3%) initiated cART during or before the first trimester, and their early MTCT was 1.2% (95% CI 0.6-1.7%). Extrapolating these data, assuming 32% EIA positivity and 2.6% or 1.2% MTCT, 832 and 384 infants per 100 000 live births were HIV infected, respectively. CONCLUSIONS: Although we demonstrate sustained national-level PMTCT impact in a high HIV prevalence setting, results are far-removed from EMTCT targets. Reducing maternal HIV prevalence and treating all maternal HIV infection early are critical for further progress.