Antibiotic and antifungal use in paediatric departments at three academic hospitals in South Africa.

Objectives: South Africa implemented a National Strategic Framework to optimise antimicrobial stewardship in 2014; however, there is limited data on how this has affected prescribing, especially to children treated in academic centres. Methods: We conducted a point prevalence survey using the World Health Organization (WHO) methodology to evaluate antibiotic and antifungal prescribing practices in paediatric departments at three academic hospitals in South Africa. Results: We recorded 1946 antimicrobial prescriptions in 1191 children, with 55.2% and 39.2% of the antibiotics classified as WHO AWaRe Access and Watch drugs, respectively. There were significant differences in prescription of Reserve antibiotics and antifungals between institutions. Receipt of WHO Watch and Reserve antibiotics was independently associated with infancy (<12 months) and adolescents (13-17 years) (adjusted relative risk [aRR]: 2.09-9.95); prolonged hospitalisation (aRR: 3.29-30.08); rapidly or ultimately fatal illness (aRR: 1.94 to 5.52); and blood transfusion (aRR: 3.28-5.70). Antifungal prescribing was associated with treatment of hospital-associated infection (aRR: 2.90), medical prophylaxis (aRR: 3.30), and treatment in intensive care units (aRR: 2.15-2.27). Conclusions: Guidance on optimisation of infection prevention and control practice and strengthening of antimicrobial stewardship would impact positively on the care of sick children in our setting.

"If you work alone on this project, you can't reach your target": unpacking the leader's role in well-performing teams in a maternal and neonatal quality improvement programme in South Africa, before and during COVID-19.

The South African National Department of Health developed a quality improvement (QI) programme to reduce maternal and neonatal mortality and still births. The programme was implemented between 2018 and 2022 in 21 purposively selected public health facilities. We conducted a process evaluation to describe the characteristics and skills of the QI team leaders of well-performing teams. The evaluation was conducted in 15 of the 21 facilities. Facilities were purposively selected and comprised semi-structured interviews with leaders at three time points; reviewing of QI documentation; and 37 intermittently conducted semi-structured interviews with the QI advisors, being QI technical experts who supported the teams. These interviews focused on participants' experiences and perceptions of how the teams performed, and performance barriers and enablers. Thematic data analysis was conducted using Atlas.ti. Variation in team performance was associated with leaders' attributes and skills. However, the COVID-19 pandemic also affected team functioning. Well-performing teams had leaders who effectively navigated COVID-19 and other challenges, who embraced QI and had sound QI skills. These leaders cultivated trust by taking responsibility for failures, correcting members' mistakes in encouraging ways, and setting high standards of care. Moreover, they promoted programme ownership among members by delegating tasks. Given the critical role leaders play in team performance and thus in the outcomes of QI programmes, efforts should focus on leader selection, training, and support.

From purists to pragmatists: a qualitative evaluation of how implementation processes and contexts shaped the uptake and methodological adaptations of a maternal and neonatal quality improvement programme in South Africa prior to, and during COVID-19.

BACKGROUND: Despite progress, maternal and neonatal mortality and still births remain high in South Africa. The South African National Department of Health implemented a quality improvement (QI) programme, called Mphatlalatsane, to reduce maternal and neonatal mortality and still births. It was implemented in 21 public health facilities, seven per participating province, between 2018 and 2022. METHODS: We conducted a qualitative process evaluation of the contextual and implementation process factors' influence on implementation uptake amongst the QI teams in 15 purposively selected facilities. Data collection included three interview rounds with the leaders and members of the QI teams in each facility; intermittent interviews with the QI advisors; programme documentation review; observation of programme management meetings; and keeping a fieldwork journal. All data were thematically analysed in Atlas.ti. Implementation uptake varied across the three provinces and between facilities within provinces. RESULTS: Between March and August 2020, the COVID-19 pandemic disrupted uptake in all provinces but affected QI teams in one province more severely than others, because they received limited pre-pandemic training. Better uptake among other sites was attributed to receiving more QI training pre-COVID-19, having an experienced QI advisor, and good teamwork. Uptake was more challenging amongst hospital teams which had more staff and more complicated MNH services, versus the primary healthcare facilities. We also attributed better uptake to greater district management support. A key factor shaping uptake was leaders' intrinsic motivation to apply QI methodology. We found that, across sites, organic adaptations to the QI methodology were made by teams, started during COVID-19. Teams did away with rapid testing of change ideas and keeping a paper trail of the steps followed. Though still using data to identify service problems, they used self-developed audit tools to record intervention effectiveness, and not the prescribed tools. CONCLUSIONS: Our study underscores the critical role of intrinsic motivation of team leaders, support from experienced technical QI advisors, and context-sensitive adaptations to maximise QI uptake when traditionally recognised QI steps cannot be followed.

Healthcare-associated Infections Drive Antimicrobial Prescribing in Pediatric Departments at Three Academic Hospitals in South Africa.

BACKGROUND: The prevalence of antimicrobial prescriptions for healthcare-associated infections (HAI) in South Africa is largely unknown. This study aimed to estimate the point prevalence of pediatric antibiotic and antifungal usage in 3 South African academic hospitals. METHODS: This cross-sectional study included hospitalized neonates and children (0-15 years). We used the World Health Organization methodology for antimicrobial point prevalence studies, with weekly surveys to achieve a sample size of ~400 at each site. RESULTS: Overall, 1,946 antimicrobials were prescribed to 1,191 patients. At least 1 antimicrobial was prescribed for 22.9% [95% confidence interval (CI): 15.5-32.5%] of patients. The prevalence of antimicrobial prescribing for HAI was 45.6%. In the multivariable analysis, relative to children 6-12 years, neonates [adjusted relative risk (aRR): 1.64; 95% CI: 1.06-2.53], infants (aRR: 1.57; 95% CI: 1.12-2.21) and adolescents (aRR: 2.18; 95% CI: 1.45-3.29) had significantly increased risk of prescriptions for HAI. Being preterm (aRR: 1.33; 95% CI: 1.04-1.70) and underweight (aRR: 1.25; 95% CI: 1.01-1.54) was predictive of antimicrobial usage for HAI. Having an indwelling device, surgery since admission, blood transfusions and classification as rapidly fatal on McCabe score also increased the risk of prescriptions for HAI. CONCLUSIONS: The high prevalence of antimicrobial prescribing for HAI to treat children with recognized risk factors in academic hospitals in South Africa is concerning. Concerted efforts need to be made to strengthen hospital-level infection prevention and control measures, with a critical review of antimicrobial usage through functional antibiotic stewardship programs to preserve the available antimicrobial armamentarium at the hospital level.

Intervention in Mothers and Newborns to Reduce Maternal and Perinatal Mortality in 3 Provinces in South Africa Using a Quality Improvement Approach: Protocol for a Mixed Method Type 2 Hybrid Evaluation.

BACKGROUND: The COVID-19 pandemic undermined gains in reducing maternal and perinatal mortality in South Africa. The Mphatlalatsane Initiative is a health system intervention to reduce mortality and morbidity in women and newborns to desired levels. OBJECTIVE: Our evaluation aims to determine the effect of various exposures, including the COVID-19 pandemic, and a system-level, complex, patient-centered quality improvement (QI) intervention (the Mphatlalatsane Initiative) on maternal and neonatal health services at 21 selected South African facilities. The objectives are to determine whether Mphatlalatsane reduces the institutional maternal mortality ratio, neonatal mortality rate, and stillbirth rate (objective 1) and improves patients' experiences (objective 2) and quality of care (objective 3). Objective 4 assesses the contextual and implementation process factors, including the COVID-19 pandemic, that shape Mphatlalatsane uptake and variation. METHODS: This study is an implementation science type 2 hybrid effectiveness, controlled before-and-after design with quantitative and qualitative components. The Mphatlalatsane intervention commenced at the end of 2019. For objective 1, intervention and control facility-level data from the District Health Information System are compared for changes in institutional maternal and neonatal mortality and stillbirth rates and associations with QI, the COVID-19 pandemic, and both. This first analysis includes data from 18 facilities, regardless of their allocation to intervention or comparison, to obtain a general idea of the effect of the COVID-19 pandemic. For objectives 2 to 3, data collectors abstract data from maternal and neonatal records, interview participants, and conduct neonatal facility assessments. For objective 4, interviews, program documentation, surveys, and observations are used to assess how contextual factors at the macro-, meso-, and microlevels explain variation in intervention uptake and outcome. The intervention dose is measured at the microlevel only in the intervention facilities. The study assesses the Mphatlalatsane Initiative from 2020 to 2022. RESULTS: From preliminary analysis, across the 3 provinces, maternal and neonatal deaths increased during the COVID-19 pandemic, whereas stillbirths remained unchanged. Maternal satisfaction with quality of care was >90%. The COVID-19 pandemic severely disrupted the QI teams functioning. However, the QI teams regained their pre-COVID-19 momentum by adapting the QI model, with advisers providing mentoring and support. Variation in adoption at the mesolevel was related to stable and motivated leadership (particularly at the facility level), poor integration into routine processes, and buy-in from senior district managers who were affected by competing priorities. Varying referral and specialist outreach systems, staff availability and development, and service delivery infrastructure are plausible factors in variable outcomes. CONCLUSIONS: Few evaluations rigorously evaluated the effect of health system interventions on improving health services and outcomes. Results will inform the scaling up of successful intervention components and strategies to mitigate the effects of the COVID-19 pandemic or similar emerging epidemics on maternal and neonatal mortality. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42041.

Early Reflections on Mphatlalatsane, a Maternal and Neonatal Quality Improvement Initiative Implemented During COVID-19 in South Africa.

Despite global progress in reducing maternal and neonatal mortality and stillbirths, much work remains to be done to achieve the Sustainable Development Goals. Reports indicate that coronavirus disease (COVID-19) disrupts the provision and uptake of routine maternal and neonatal health care (MNH) services and negatively impacts cumulative pre-COVID-19 achievements. We describe a multipartnered MNH quality improvement (QI) initiative called Mphatlalatsane, which was implemented in South Africa before and during the COVID-19 pandemic. The initiative aimed to reduce the maternal mortality ratio, neonatal mortality rate, and stillbirth rate by 50% between 2018 and 2022. The multifaceted design comprises QI and other intervention activities across micro-, meso-, and macrolevels, and its area-based approach facilitates patients' access to MNH services. The initiative commenced 6 months pre-COVID-19, with subsequent adaptation necessitated by COVID-19. The initial focus on a plan-do-study-act QI model shifted toward meeting the immediate needs of health care workers (HCWs), the health system, and health care managers arising from COVID-19. Examples include providing emotional support to staff and streamlining supply chain management for infection control and personal protection materials. As these needs were addressed, Mphatlalatsane gradually refocused HCWs' and managers' attention to recognize the disruptions caused by COVID-19 to routine MNH services. This gradual reprioritization included the development of a risk matrix to help staff and managers identify specific risks to service provision and uptake and develop mitigating measures. Through this approach, Mphatlalatsane led to an optimization case using existing resources rather than requesting new resources to build an investment case, with a responsive design and implementation approach as the cornerstone of the initiative. Further, Mphatlalatsane demonstrates that agile and context-specific responses to crises such as the COVID-19 pandemic can mitigate such threats and maintain interventions to improve MNH services.

The impact of continuous quality improvement on coverage of antenatal HIV care tests in rural South Africa: Results of a stepped-wedge cluster-randomised controlled implementation trial.

BACKGROUND: Evidence for the effectiveness of continuous quality improvement (CQI) in resource-poor settings is very limited. We aimed to establish the effects of CQI on quality of antenatal HIV care in primary care clinics in rural South Africa. METHODS AND FINDINGS: We conducted a stepped-wedge cluster-randomised controlled trial (RCT) comparing CQI to usual standard of antenatal care (ANC) in 7 nurse-led, public-sector primary care clinics-combined into 6 clusters-over 8 steps and 19 months. Clusters randomly switched from comparator to intervention on pre-specified dates until all had rolled over to the CQI intervention. Investigators and clusters were blinded to randomisation until 2 weeks prior to each step. The intervention was delivered by trained CQI mentors and included standard CQI tools (process maps, fishbone diagrams, run charts, Plan-Do-Study-Act [PDSA] cycles, and action learning sessions). CQI mentors worked with health workers, including nurses and HIV lay counsellors. The mentors used the standard CQI tools flexibly, tailored to local clinic needs. Health workers were the direct recipients of the intervention, whereas the ultimate beneficiaries were pregnant women attending ANC. Our 2 registered primary endpoints were viral load (VL) monitoring (which is critical for elimination of mother-to-child transmission of HIV [eMTCT] and the health of pregnant women living with HIV) and repeat HIV testing (which is necessary to identify and treat women who seroconvert during pregnancy). All pregnant women who attended their first antenatal visit at one of the 7 study clinics and were ≥18 years old at delivery were eligible for endpoint assessment. We performed intention-to-treat (ITT) analyses using modified Poisson generalised linear mixed effects models. We estimated effect sizes with time-step fixed effects and clinic random effects (Model 1). In separate models, we added a nested random clinic-time step interaction term (Model 2) or individual random effects (Model 3). Between 15 July 2015 and 30 January 2017, 2,160 participants with 13,212 ANC visits (intervention n = 6,877, control n = 6,335) were eligible for ITT analysis. No adverse events were reported. Median age at first booking was 25 years (interquartile range [IQR] 21 to 30), and median parity was 1 (IQR 0 to 2). HIV prevalence was 47% (95% CI 42% to 53%). In Model 1, CQI significantly increased VL monitoring (relative risk [RR] 1.38, 95% CI 1.21 to 1.57, p < 0.001) but did not improve repeat HIV testing (RR 1.00, 95% CI 0.88 to 1.13, p = 0.958). These results remained essentially the same in both Model 2 and Model 3. Limitations of our study include that we did not establish impact beyond the duration of the relatively short study period of 19 months, and that transition steps may have been too short to achieve the full potential impact of the CQI intervention. CONCLUSIONS: We found that CQI can be effective at increasing quality of primary care in rural Africa. Policy makers should consider CQI as a routine intervention to boost quality of primary care in rural African communities. Implementation research should accompany future CQI use to elucidate mechanisms of action and to identify factors supporting long-term success. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov under registration number NCT02626351.

Evaluation of a health system intervention to improve virological management in an antiretroviral programme at a municipal clinic in central Durban.

BACKGROUND: With the largest antiretroviral therapy (ART) programme globally, demand for effective HIV management is increasing in South Africa. While viral load (VL) testing is conducted, VL follow-up and management are sub-optimal. OBJECTIVES: The objective of this study was to address gaps in the VL cascade to improve VL testing and management. METHODS: Antiretroviral therapy records were sampled for an in-depth review. The study team then reviewed individual records, focusing on ART management, virological suppression and retention. Multifaceted interventions focused on virological control, including a clinical summary chart for ART care; streamlining laboratory results receipt and management; monitoring VL suppression, flagging virological failure and missed visits for follow-up; down-referral of stable patients eligible for the chronic club system; and training of personnel and patients. RESULTS: Pre-intervention, 78% (94/120) of eligible patients had VL tests, versus 92% (145/158) post-intervention (p = 0.0009). Pre-intervention, 59% (71/120) of patients accessed their VL results, versus 86% (136/158) post-intervention (p < 0.0001). Post-intervention, 73% (19/26) of patients eligible for ART change were appropriately managed, versus 11% (4/36) pre-intervention (p < 0.0001). Only 27% had no regimen changes (7/26) post-intervention, versus 81% (29/36) pre-intervention (p < 0.0001). CONCLUSION: Service delivery was streamlined to facilitate HIV services by focusing on VL test monitoring, protocol training and accessibility of results, thereby improving clinical management.

The MONARCH intervention to enhance the quality of antenatal and postnatal primary health services in rural South Africa: protocol for a stepped-wedge cluster-randomised controlled trial.

BACKGROUND: Gaps in maternal and child health services can slow progress towards achieving the Sustainable Development Goals. The Management and Optimization of Nutrition, Antenatal, Reproductive, Child Health & HIV Care (MONARCH) study will evaluate a Continuous Quality Improvement (CQI) intervention targeted at improving antenatal and postnatal health service outcomes in rural South Africa where HIV prevalence among pregnant women is extremely high. Specifically, it will establish the effectiveness of CQI on viral load (VL) testing in pregnant women who are HIV-positive and repeat HIV testing in pregnant women who are HIV-negative. METHODS: This is a stepped-wedge cluster-randomised controlled trial (RCT) of 7 nurse-led primary healthcare clinics to establish the effect of CQI on selected routine antenatal and postnatal services. Each clinic was a cluster, with the exception of the two smallest clinics, which jointly formed one cluster. The intervention was applied at the cluster level, where staff received training on CQI methodology and additional mentoring as required. In the control exposure state, the clusters received the South African Department of Health standard of care. After a baseline data collection period of 2 months, the first cluster crossed over from control to intervention exposure state; subsequently, one additional cluster crossed over every 2 months. The six clusters were divided into 3 groups by patient volume (low, medium and high). We randomised the six clusters to the sequences of crossing over, such that both the first three and the last three sequences included one cluster with low, one with medium, and one with high patient volume. The primary outcome measures were (i) viral load testing among pregnant women who were HIV-positive, and (ii) repeat HIV testing among pregnant women who were HIV-negative. Consenting women ≥18 years attending antenatal and postnatal care during the data collection period completed outcome measures at delivery, and postpartum at three to 6 days, and 6 weeks. Data collection started on 15 July 2015. The total study duration, including pre- and post-exposure phases, was 19 months. Data will be analyzed by intention-to-treat based on first booked clinic of study participants. DISCUSSION: The results of the MONARCH trial will establish the effectiveness of CQI in improving antenatal and postnatal clinic processes in primary care in sub-Saharan Africa. More generally, the results will contribute to our knowledge on quality improvement interventions in resource-poor settings. TRIAL REGISTRATION: This trial was registered on 10 December 2015: www.clinicaltrials.gov, identifier NCT02626351 .

Preterm delivery and small-for-gestation outcomes in HIV-infected pregnant women on antiretroviral therapy in rural South Africa: Results from a cohort study, 2010-2015.

OBJECTIVES: Increasingly more women conceive on antiretroviral therapy (ART) with non-nucleoside reverse transcriptase-based regimens. This study assessed the effect of preconception tenofovir disoproxil fumarate (TDF)-lamivudine (3TC)/emtricitabine (FTC)-efavirenz (EFV) and post-conception TDF-(3TC/FTC)-EFV (versus other regimens) on preterm delivery (PTD) and small-for-gestational age (SGA) births. METHODS: We analysed data of 2549 HIV-infected women attending antenatal clinics in KwaZulu-Natal from 2010 through 2015 in this retrospective cohort study. Preconception, TDF-(3TC/FTC)-EFV was compared to nevirapine (NVP)-based regimens and other 3-drug EFV-based regimens. Post-conception, TDF-(3TC/FTC)-EFV was compared to NVP-based ART and zidovudine (ZDV) prophylaxis. Outcomes included PTD <37 weeks and SGA births. Generalized linear mixed effects were used to fit logistic regression models to account for repeat pregnancies. RESULTS: Among 2549 singleton live births, 10.4% (n = 264) were PTD and 10.4% (n = 265) SGA. PTD declined from 16.3% in 2010 to 9.3% in 2015 and SGA remained stable from 9.9% in 2010 to 10% in 2015. Preconception NVP-based regimens [adjusted odds ratio (aOR) 0.66; 95% CI 0.27-1.63] and other 3-drug EFV-based regimens (aOR 0.72; 95% CI 0.24-2.12) were not associated with PTD versus TDF-(3TC/FTC)-EFV. NVP-based (aOR 0.75; 95% CI 0.40-1.42) and other 3-drug EFV-based regimens (aOR 1.55; 95% CI 0.76-3.16) were not associated with SGA births versus TDF-(3TC/FTC)-EFV. Post-conception NVP-based ART (1.77; 95% CI 0.89-3.51) and ZDV (1.03; 95% CI 0.68-1.58) were not associated with PTD versus TDF-(3TC/FTC)-EFV. NVP-based ART (1.55; 95% CI 0.66-3.61) and ZDV (0.89; 95% CI 0.53-1.47) were not associated with SGA versus TDF-(3TC/FTC)-EFV. CONCLUSIONS: Preconception TDF-(3TC/FTC)-EFV and post-conception TDF-(3TC/FTC)-EFV were not associated with PTD or SGA, compared with other regimens. Increasing ART use merits further study of the optimum ART regimen for safe birth outcomes.

Viraemia before, during and after pregnancy in HIV-infected women on antiretroviral therapy in rural KwaZulu-Natal, South Africa, 2010-2015.

OBJECTIVES: Pregnancy and post-partum viral load suppression is critical to prevent mother-to-child HIV transmission and ensure maternal health. We measured viraemia risk before, during and after pregnancy in HIV-infected women. METHODS: Between 2010 and 2015, 1425 HIV-infected pregnant women on lifelong antiretroviral therapy (ART) for at least six months pre-pregnancy were enrolled in a cohort study in rural KwaZulu-Natal, South Africa. Odds ratios were estimated in multilevel logistic regression, with pregnancy period time-varying. RESULTS: Over half of 1425 women received tenofovir-based regimens (n = 791). Median pre-pregnancy ART duration was 2.1 years. Of 988 women (69.3%) with pre-pregnancy viral loads, 82.0%, 6.8% and 11.2% had VL <50, 50-999 and ≥1000 copies/ml, respectively. During pregnancy and at six, 12 and 24 months, viral load was ≥1000 copies/ml in 15.2%, 15.7%, 17.8% and 16.6% respectively; viral load <50 was 76.9%, 77%, 75.5% and 75.8%, respectively. Adjusting for age, clinical and pregnancy factors, viraemia risk (viral load ≥50 copies/ml) was not significantly associated with pregnancy [adjusted OR (aOR) 1.31; 95% CI 0.90-1.92], six months (aOR 1.30; 95% CI 0.83-2.04), 12 months (aOR 0.96; 95% CI 0.58-1.58) and 24 months (aOR 1.40; 95% CI 0.89-2.22) post-partum. Adjusting for ART duration-pregnancy period interaction, viraemia risk was 1.8 during pregnancy and twofold higher post-partum. CONCLUSIONS: While undetectable viral load before pregnancy through post-partum was common, the UNAIDS goal to suppress viraemia in 90% of women was not met. Women on preconception ART remain vulnerable to viraemia; additional support is required to prevent mother-to-child HIV transmission and maintain maternal health.

Incident HIV during pregnancy and early postpartum period: a population-based cohort study in a rural area in KwaZulu-Natal, South Africa.

BACKGROUND: The evidence on the effect of pregnancy on acquiring HIV is conflicting, with studies reporting both higher and lower HIV acquisition risk during pregnancy when prolonged antiretroviral therapy was accessible. The aim of this study was to assess the pregnancy effect on HIV acquisition where antiretroviral therapy was widely available in a high HIV prevalence setting. METHODS: This is a retrospective cohort study nested within a population-based surveillance to determine HIV incidence in HIV-uninfected women from 15 to 49 years from 2010 through 2015 in rural KwaZulu-Natal. HIV incidence per 100 person-years according to pregnancy status (not pregnant, pregnant, to eight weeks postpartum) were measured in 5260 HIV-uninfected women. Hazard ratios (HR) were estimated by Cox proportional hazards regression with pregnancy included as a time varying variable. RESULTS: Overall, pregnancy HIV incidence was 4.5 per 100 person-years (95% CI 3.4-5.8), higher than non-pregnancy (4.0; 95% CI 3.7-4.3) and postpartum incidences (4.2 per 100 person-years; 95% CI 2.3-7.6). However, adjusting for age, and demographic factors, pregnant women had a lower risk of acquiring HIV (HR 0.4; 95% CI 0.2-0.9, P = 0.032) than non-pregnant women; there were no differences between postpartum and non-pregnant women (HR 1.2; 95% CI 0.4-3.2; P = 0.744). In models adjusting for the interaction of age and gravidity, pregnant women under 25 years with two or more pregnancies had a 2.3 times greater risk of acquiring HIV than their older counterparts (95% CI 1.3-4.3; P = 0.008). CONCLUSIONS: Pregnancy had a protective effect on HIV acquisition. Elevated HIV incidence in younger women appeared to be driven by those with higher gravidity. The sexual and biological factors in younger women should be explored further in order to design appropriate HIV prevention interventions.

Cohort profile: the Hlabisa pregnancy cohort, KwaZulu-Natal, South Africa.

PURPOSE: The Hlabisa pregnancy cohort was established to evaluate the effectiveness of prevention of mother-to-child transmission (PMTCT) guideline revisions. The objectives of the Hlabisa pregnancy cohort are to: (1) provide cohort-level information on maternal health up to 6 weeks postpartum in a high HIV prevalence setting; and to (2) evaluate aspects of PMTCT care that have policy relevance. PARTICIPANTS: The pregnancy cohort is located in primary health clinics in the Hlabisa subdistrict of rural KwaZulu-Natal, South Africa. Baseline data collection between 2010 and 2014 has been completed with the enrolment of 25 608 pregnancies; age ranged from 15-49 years. Pregnant women were assessed during routine antenatal visits: first visit, follow-up 1 week later, 32 weeks (HIV test), infant delivery and 6 weeks postpartum. Demographic, pregnancy, clinical, laboratory and HIV data were collected through Department of Health interviews, laboratory tests and routine data linkage. Treatment data for HIV-infected pregnant women were linked to the Africa Centre Hlabisa HIV Treatment and Care Programme for detailed antiretroviral therapy (ART) history and laboratory tests. FINDINGS TO DATE: The proportion of women initiated on ART post-2013 were higher (n=437; 100%) than pre-2013 (n=768; 84.2%). The proportion of women in care at 6 weeks (73.8%) was also higher post-2013 relative to earlier years (58.5%). The majority of HIV-infected pregnant women were either on lifelong ART or ART prophylaxis; pre-2013, ∼ 9.6% of women were not on any ART. Pregnancy viral load monitoring was inadequate. FUTURE PLANS: This cohort will be used to: (1) determine HIV acquisition risk during pregnancy and postpartum; (2) determine the effect of HIV and ART on birth outcomes; (3) examine the effect of pregnancy on virological response to ART; and (4) characterise the effect of sequential pregnancies on access to clinical care, response to prolonged ART and birth outcomes.

Preventing unintended pregnancy and HIV transmission: effects of the HIV treatment cascade on contraceptive use and choice in rural KwaZulu-Natal.

BACKGROUND: For women living with HIV, contraception using condoms is recommended because it prevents not only unintended pregnancy but also acquisition of other sexually transmitted infections and onward transmission of HIV. Dual-method dual-protection contraception (condoms with other contraceptive methods) is preferable over single-method dual-protection contraception (condoms alone) because of its higher contraceptive effectiveness. We estimate the effect of progression through the HIV treatment cascade on contraceptive use and choice among HIV-infected women in rural South Africa. METHODS: We linked population-based surveillance data on contraception collected by the Wellcome Trust Africa Centre for Health and Population Studies to data from the local antiretroviral treatment (ART) program in Hlabisa subdistrict, KwaZulu-Natal. In bivariate probit regression, we estimated the effects of progressing through the cascade on contraceptive choice among HIV-infected sexually active women aged 15-49 years (N = 3169), controlling for a wide range of potential confounders. FINDINGS: Contraception use increased across the cascade from <40% among HIV-infected women who did not know their status to >70% among women who have been on ART for 4-7 years. Holding other factors equal (1) awareness of HIV status, (2) ART initiation, and (3) being on ART for 4-7 years increased the likelihood of single-method/dual-method dual protection by the following percentage points (pp), compared with women who were unaware of their HIV status: (1) 4.6 pp (P = 0.030)/3.5 pp (P = 0.001), (2) 10.3 pp (P = 0.003)/5.2 pp (P = 0.007), and (3) 21.6 pp (P < 0.001)/11.2 pp (P < 0.001). CONCLUSIONS: Progression through the HIV treatment cascade significantly increased the likelihood of contraception in general and contraception with condoms in particular. ART programs are likely to contribute to HIV prevention through the behavioral pathway of changing contraception use and choice.

HIV status, breastfeeding modality at 5 months and postpartum maternal weight changes over 24 months in rural South Africa.

OBJECTIVE: To determine the effect of infant feeding practices on postpartum weight change among HIV-infected and -uninfected women in South Africa. METHODS: In a non-randomised intervention cohort study of antiretroviral therapy-naïve women in South Africa, infants were classified as exclusive (EBF), mixed (MF) or non-breastfed (NBF) at each visit. We analysed infant feeding cumulatively from birth to 5 months using 24-hour feeding history (collected weekly for each of the preceding 7 days). Using generalised estimating equation mixed models, allowing for repeated measures, we compared postpartum weight change (kg) from the first maternal postpartum weight within the first 6 weeks (baseline weight) to each subsequent visit through 24 months among 2340 HIV-infected and -uninfected women with live births and at least two postpartum weight measurements. RESULTS: HIV-infected (-0.2 kg CI: -1.7 to 1.3 kg; P = 0.81) and -uninfected women (-0.5 kg; 95% CI: -2.1 to 1.2 kg; P = 0.58) had marginal non-significant weight loss from baseline to 24 months postpartum. Adjusting for HIV status, socio-demographic, pregnancy-related and infant factors, 5-month feeding modality was not significantly associated with postpartum weight change: weight change by 24 months postpartum, compared to the change in the reference EBF group, was 0.03 kg in NBF (95% CI: -2.5 to +2.5 kg; P = 0.90) and 0.1 kg in MF (95% CI: -3.0 to +3.2 kg; P = 0.78). CONCLUSION: HIV-infected and -uninfected women experienced similar weight loss over 24 months. Weight change postpartum was not associated with 5-month breastfeeding modality among HIV-infected and -uninfected women.

Southern African Treatment Resistance Network (SATuRN) RegaDB HIV drug resistance and clinical management database: supporting patient management, surveillance and research in southern Africa.

Substantial amounts of data have been generated from patient management and academic exercises designed to better understand the human immunodeficiency virus (HIV) epidemic and design interventions to control it. A number of specialized databases have been designed to manage huge data sets from HIV cohort, vaccine, host genomic and drug resistance studies. Besides databases from cohort studies, most of the online databases contain limited curated data and are thus sequence repositories. HIV drug resistance has been shown to have a great potential to derail the progress made thus far through antiretroviral therapy. Thus, a lot of resources have been invested in generating drug resistance data for patient management and surveillance purposes. Unfortunately, most of the data currently available relate to subtype B even though >60% of the epidemic is caused by HIV-1 subtype C. A consortium of clinicians, scientists, public health experts and policy markers working in southern Africa came together and formed a network, the Southern African Treatment and Resistance Network (SATuRN), with the aim of increasing curated HIV-1 subtype C and tuberculosis drug resistance data. This article describes the HIV-1 data curation process using the SATuRN Rega database. The data curation is a manual and time-consuming process done by clinical, laboratory and data curation specialists. Access to the highly curated data sets is through applications that are reviewed by the SATuRN executive committee. Examples of research outputs from the analysis of the curated data include trends in the level of transmitted drug resistance in South Africa, analysis of the levels of acquired resistance among patients failing therapy and factors associated with the absence of genotypic evidence of drug resistance among patients failing therapy. All these studies have been important for informing first- and second-line therapy. This database is a free password-protected open source database available on www.bioafrica.net. Database URL: http://www.bioafrica.net/regadb/

A retrospective study of Human Immunodeficiency Virus transmission, mortality and loss to follow-up among infants in the first 18 months of life in a prevention of mother-to-child transmission programme in an urban hospital in KwaZulu-Natal, South Africa.

BACKGROUND: Follow up of Human Immunodeficiency Virus (HIV)-exposed infants is an important component of Prevention of Mother-to-Child Transmission (PMTCT) programmes in order to ascertain infant outcomes post delivery. We determined HIV transmission, mortality and loss to follow-up (LTFU) of HIV-exposed infants attending a postnatal clinic in an urban hospital in Durban, South Africa. METHODS: We conducted a retrospective cohort study of infants born to women in the PMTCT programme at McCord Hospital, where mothers paid a fee for service. Data were abstracted from patient records for live-born infants delivered between 1 May 2008 and 31 May 2009. The infants' LTFU status and age was based on the date of the last visit. HIV transmission was calculated as a proportion of infants followed and tested at six weeks. Mortality rates were analyzed using Kaplan-Meier (K-M), with censoring on 15 January 2010, LTFU or death. RESULTS: Of 260 infants, 155 (59.6%) remained in care at McCord beyond 28 weeks: one died at < 28 days, three died between one to six months; 34 were LTFU within seven days, 60 were LTFU by six months. K-M mortality rate: 1.7% at six months (95% confidence interval (CI): 0.6% to 4.3%). Of 220 (83%) infants tested for HIV at six weeks, six (2.7%, 95% CI: 1.1% to 5.8%) were HIV-infected. In Cox regression analysis, late antenatal attendance (≥ 28 weeks gestation) relative to attending in the first trimester was a predictor for infant LTFU (adjusted hazards ratio = 2.3; 95% CI: 1.0 to 5.1; p = 0.044). CONCLUSION: This urban PMTCT programme achieved low transmission rates at six weeks, but LTFU in the first six months limited our ability to examine HIV transmission up to 18 months and determinants of mortality. The LTFU of infants born to women who attended antenatal care at 28 weeks gestation or later emphasizes the need to identify late antenatal attendees for follow up care to educate and support them regarding the importance of follow up care for themselves and their infants.