Compliance to Viral Load Monitoring Schedules Among Women Attending Prevention of Vertical HIV Transmission Services Before and During the COVID-19 Pandemic in Ehlanzeni District, Mpumalanga, South Africa.

Human immunodeficiency virus (HIV) viral load (VL) monitoring was likely interrupted during the Coronavirus disease 2019 (COVID-19) pandemic. We used routine data on repeat VL testing among 667 prevention of vertical HIV transmission (PVT) clients in Ehlanzeni district, to determine compliance to VL testing recommendations and associated factors during different time periods: pre-COVID-19, transition, and COVID-19. Descriptive and multivariable Poisson regression analyses were conducted, with and without including revised PVT-guidelines rolled out in January-2020. Among 405 women with ≥ 2 VL tests, the overall median age was 30 years (interquartile range: 26-35 years). Compliance to recommended VL testing guidelines ranged between 81.5% (172/211) and 92.3% (191/207) at different time periods. Across all three periods and when revised PVT-guidelines were used, being compliant was significantly reduced among those with earliest VL = 50-999 copies/ml (incidence rate ratio (IRR) = 0.71 [95% confidence interval (CI) 0.61-0.82], p value < 0.001) and VL ≥ 1000 copies/ml (IRR = 0.18 [95% CI 0.09-0.36], p value < 0.001). When guideline revisions were excluded, compliance was only significantly reduced among those with VL ≥ 1000 copies/ml (IRR = 0.14 [95% CI 0.06-0.32], p value < 0.001) and increased during the COVID-19 period versus pre-COVID-19 (IRR = 1.10 [95% CI 1.05-1.15], p value < 0.001). Similar significant associations between compliance and VL level were observed when the COVID-19 period was analyzed separately. Significantly increased compliance to VL testing among the 25-34 years age-group versus younger women was also observed across all periods. These results highlight the importance of strengthening strategies such as short message service reminders and educational messaging, reaching all age-groups, to fast-track implementation targets for VL monitoring.

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.

Seroprevalence survey of anti-SARS-CoV-2 antibody and associated factors in South Africa: Findings of the 2020-2021 population-based household survey.

Population-based serological testing is important to understand the epidemiology and estimate the true cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to inform public health interventions. This study reports findings of a national household population SARS-CoV-2 serosurvey in people 12 years and older in South Africa. This cross-sectional multi-stage random stratified cluster survey undertaken from November 2020 to June 2021 collected sociodemographic data, medical history, behavioural data, and blood samples from consenting participants. The samples were tested for SARS-CoV-2 antibodies using the Roche ElecsysAnti-SARS-CoV-2 chemiluminescence immunoassay (CLIA) Total Antibody Test. The survey data were weighted by age, race, sex, and province with final individual weights benchmarked against the 2020 mid-year population estimates and accounted for clustering. Descriptive statistics summarize the characteristics of participants and seroprevalence. Logistic regression analyses were used to identify factors associated with seropositivity. From 13290 survey participants (median age 33 years, interquartile range (IQR) 23-46 years), SARS-CoV-2 seroprevalence was 37.8% [95% Confidence Interval (CI) 35.4-40.4] and varied substantially across the country's nine provinces, and by sex, age and locality type. In the final adjusted model, the odds of seropositivity were higher in women than in men [aOR = 1.3 (95% CI: 1.0-1.6), p = 0.027], and those living with HIV (self-report) [aOR = 1.6 (95% CI: 1.0-2.4), p = 0.031]. The odds were lower among those 50 years and older compared to adolescents 12-19 years old [aOR = 0.6 (95% CI: 0.5-0.8), p<0.001] and in those who did not attend events or gatherings [aOR = 0.7 (95% CI: 0.6-1.0), p = 0.020]. The findings help us understand the epidemiology of SARS-CoV-2 within different regions in a low-middle-income country. The survey highlights the higher risk of infection in women in South Africa likely driven by their home and workplace roles and also highlighted a need to actively target and include younger people in the COVID-19 response.

Male partner unknown HIV status as a risk factor for HIV incidence and clinical outcomes in prevention of mother-to-child transmission of HIV programmes in 21 WHO priority countries: a systematic review protocol.

INTRODUCTION: Research has shown an association between increased disclosure of HIV status by pregnant and breastfeeding women and improved clinical health and that of their infant. Increasing awareness about their male partner's HIV status will no doubt lead to even better outcomes at the population level. Male partner involvement is important for improving outcomes of prevention of mother-to-child transmission of HIV (MTCT) as it improves social support and commitment from both parents of the baby to ensure sustained good health. Although lack of knowledge of the HIV status of a male partner is of great concern, limited research has been done to determine whether it remains one of the barriers to reaching the proposed goals of eliminating MTCT in pregnant or postpartum women. Our aim is to determine if lack of knowledge of a male partner's HIV status is a significant risk factor for HIV incidence and poor HIV clinical outcomes among pregnant women and postpartum women and their infants. METHODS AND ANALYSIS: A systematic review and meta-analysis of experimental and observational studies will be conducted. The review will focus on knowledge of male partner's HIV status in the 21 priority countries most affected by HIV in Africa. We will search electronic databases such as PubMed/Medline, Scopus, Web of Science and Cochrane library, Science Direct, CINAHL, LILACS and SciELO databases from January 2011 to December 2021. We will also search the Pan African and WHO clinical trial registries and conference archives. We will conduct a quality assessment of eligible studies and evaluate the heterogeneity of the pooled studies using the I 2 statistic. The statistical analysis will be performed using STATA statistical software V.16. ETHICS AND DISSEMINATION: The study will use publicly available data and ethics exemption has been obtained from Human Research Ethics Committees, Faculty of Medicine & Health Sciences, Stellenbosch University. The protocol was registered on Prospective Register of Systematic Reviews, registration number CRD42021247686, in May 2021. Findings of this systematic review will be disseminated in peer-review journals including various media platforms, that is, webinars, symposia, conferences or congresses. PROSPERO REGISTRATION NUMBER: Registration number CRD42021247686.

HIV viral load non-suppression and associated factors among pregnant and postpartum women in rural northeastern South Africa: a cross-sectional survey.

OBJECTIVES: We aimed to measure the prevalence of maternal HIV viral load (VL) non-suppression and assess associated factors, to evaluate progress towards United Nations-AIDS (UNAIDS) targets. DESIGN: Cross-sectional study. SETTING: The eight largest community health centres of Ehlanzeni, a rural district in northeast South Africa. PARTICIPANTS: Pregnant women living with HIV (WLHIV) in their third trimester and postpartum WLHIV and their biological infants, recruited equally across all stages of the first 24 months post partum, were included. A sample of 612 mothers participated from a target of 1000. PRIMARY OUTCOME MEASURES: The primary outcome was maternal VL (mVL) non-suppression (defined here as mVL >1000 copies/mL). We collected information on antiretroviral use, healthcare visits and sociodemographics through interviews and measured plasma mVL. Descriptive statistics, χ2 tests and multivariable logistic regression analysis were conducted. RESULTS: All mothers (median age: 30 years) were on antiretroviral therapy (ART) and 24.9% were on ART ≤12 months. The prevalence of mVL non-suppression was 14.7% (95% CI: 11.3% to 19.0%), while 13.8% had low-level viraemia (50-1000 copies/mL). Most (68.9%) women had initiated breast feeding and 37.6% were currently breast feeding their infants. Being younger than 25 years (adjusted odds ratio (AOR): 2.6 (95% CI: 1.1 to 6.4)), on first-line ART (AOR: 2.3 (95% CI: 1.1 to 4.6)) and married/cohabiting (AOR: 1.9 (95% CI: 1.0 to 3.7)) were significantly associated with increased odds of mVL non-suppression. CONCLUSIONS: The prevalence of mVL ≤1000 copies/mL of 85.3% among pregnant and postpartum WLHIV and attending public healthcare centres in this rural district is below the 2020 90-90-90 and 2030 95-95-95 UNAIDS targets. Given that low-level viraemia may also increase the risk of vertical HIV transmission, we recommend strengthened implementation of the new guidelines which include better ART options, improved ART regimen switching and mVL monitoring schedules, and intensified psychosocial support for younger women, while exploring district-level complementary interventions, to sustain VLs below 50 copies/mL among all women.

Hospital acquired COVID-19 infections amongst patients before the rollout of COVID-19 vaccinations, a scoping review.

BACKGROUND: Hospital settings are at increased risk of spreading Coronavirus Disease 2019 (COVID-19) infections, hence non-pharmaceutical prevention interventions (NPPIs) and prioritized vaccination of healthcare workers and resident patients are critical. The status of COVID-19 hospital acquired infections (HAIs) in low-income settings is unclear. We aimed to identify and summarize the existing evidence on COVID-19 HAIs amongst patients, prior to the rollout of vaccines in countries worldwide. METHODS: We conducted a scoping review of English peer-reviewed literature in PubMed, Web of Science and Scopus using a combination of selected search terms. Full texts articles presenting results on COVID-19 HAIs in hospitalised patients before the rollout of vaccines in countries worldwide were eligible. Data extracted from eligible articles included estimates of COVID-19 HAIs, country, and type of hospital setting, and was summarized narratively. Quality assessment of included articles was not possible. RESULTS: Literature searches generated a total of 5920 articles, and 45 were eligible for analysis. Eligible articles were from Europe, North America, Asia, and Brazil and none were from low-income countries. The proportion of COVID-19 HAIs ranged from 0% when strict NPPIs were applied, to 65% otherwise. The estimates of COVID-19 HAIs did not differ by country but were lower in studies conducted after implementation of NPPIs and in specialized hospital settings for operative surgery. Studies conducted before the implementation of NPPIs or in long-term care and psychiatric wards often reported high estimates of HAI. Although there was no clear trend in general wards, those situated in academic hospitals managed to reduce HAI rates under strict NPPI protocols. Operative surgery settings, unlike psychiatric settings, effectively prevented COVID-19 HAI using tailored NPPIs. CONCLUSION: The available evidence shows a high risk of COVID-19 HAIs, the feasibility of preventing HAIs in different healthcare settings and the importance of appropriately tailored NPPIs. There were no data from low-income settings, therefore, it is unclear whether the reported NPPI approaches could be equally effective elsewhere. We recommend routine monitoring of COVID-19 HAIs in countries with low vaccination coverage, to identify and close gaps in NPPIs and understand gains made from vaccinating healthcare workers and hospitalized patients.

Eliminating postnatal HIV transmission in high incidence areas: need for complementary biomedical interventions.

The rate of mother-to-child transmission (MTCT) of HIV from breastfeeding is increasing relative to other causes of MTCT. Early effective preconception and antenatal antiretroviral therapy (ART) reduces intrauterine and intrapartum MTCT, whereas maternal post-partum HIV acquisition, untreated maternal HIV, and suboptimal postnatal maternal ART adherence increase the risk of MTCT through breastfeeding. Although the absolute number of cases of MTCT acquired through breastfeeding is decreasing, the rate of decrease is less than the decrease in intrauterine and intrapartum MTCT. Unless current strategies are universally applied, they might not be sufficient to eliminate MTCT due to breastfeeding. Urgent action is needed to evaluate and implement additional preventive biomedical strategies in high HIV prevalence and incidence settings to eliminate MTCT from breastfeeding. Preventive strategies include: pre-exposure prophylaxis in breastfeeding women who have an increased risk of acquiring HIV; postnatal reinforcement strategies, such as maternal retesting for HIV, maternal care reinforcement, and prophylaxis in infants exposed to HIV via breastmilk; and active (vaccine) or passive immunoprophylaxis with long-acting broadly neutralising antibodies.

Impact of breastfeeding, maternal antiretroviral treatment and health service factors on 18-month vertical transmission of HIV and HIV-free survival: results from a nationally representative HIV-exposed infant cohort, South Africa.

BACKGROUND: We analysed the impact of breastfeeding, antiretroviral drugs and health service factors on cumulative (6 weeks to 18 months) vertical transmission of HIV (MTCT) and 'MTCT-or-death', in South Africa, and compared estimates with global impact criteria to validate MTCT elimination: (1) <5% final MTCT and (2) case rate ≤50 (new paediatric HIV infections/100 000 live births). METHODS: 9120 infants aged 6 weeks were enrolled in a nationally representative survey. Of 2811 HIV-exposed uninfected infants (HEU), 2644 enrolled into follow-up (at 3, 6, 9, 12, 15 and 18 months). Using Kaplan-Meier analysis and weighted survey domain-based Cox proportional hazards models, we estimated cumulative risk of MTCT and 'MTCT or death' and risk factors for time-to-event outcomes, adjusting for study design and loss-to-follow-up. RESULTS: Cumulative (final) MTCT was 4.3% (95% CI 3.7% to 5.0%); case rate was 1290. Postnatal MTCT (>6 weeks to 18 months) was 1.7% (95% CI 1.2% to 2.4%). Cumulative 'MTCT-or-death' was 6.3% (95% CI 5.5% to 7.3%); 81% and 62% of cumulative MTCT and 'MTCT-or-death', respectively, occurred by 6 months. Postnatal MTCT increased with unknown maternal CD4-cell-count (adjusted HR (aHR 2.66 (1.5-5.6)), undocumented maternal HIV status (aHR 2.21 (1.0-4.7)) and exclusive (aHR 2.3 (1.0-5.2)) or mixed (aHR 3.7 (1.2-11.4)) breastfeeding. Cumulative 'MTCT-or death' increased in households with 'no refrigerator' (aHR 1.7 (1.1-2.9)) and decreased if infants used nevirapine at 6 weeks (aHR 0.4 (0.2-0.9)). CONCLUSIONS: While the <5% final MTCT target was met, the case rate was 25-times above target. Systems are needed in the first 6 months post-delivery to optimise HEU health and fast-track ART initiation in newly diagnosed mothers.

Mitochondrial DNA Parameters in Blood of Infants Receiving Lopinavir/Ritonavir or Lamivudine Prophylaxis to Prevent Breastfeeding Transmission of HIV-1.

Children who are human immunodeficiency virus (HIV)-exposed but uninfected (CHEU) accumulate maternal HIV and antiretroviral exposures through pregnancy, postnatal prophylaxis, and breastfeeding. Here, we compared the dynamics of mitochondrial DNA (mtDNA) parameters in African breastfed CHEU receiving lopinavir/ritonavir (LPV/r) or lamivudine (3TC) pre-exposure prophylaxis during the first year of life. The number of mtDNA copies per cell (MCN) and the proportion of deleted mtDNA (MDD) were assessed at day 7 and at week 50 post-delivery (PrEP group). mtDNA depletion was defined as a 50% or more decrease from the initial value, and mtDNA deletions was the detection of mtDNA molecules with large DNA fragment loss. We also performed a sub-analysis with CHEU who did not receive a prophylactic treatment in South Africa (control group). From day seven to week 50, MCN decreased with a median of 41.7% (interquartile range, IQR: 12.1; 64.4) in the PrEP group. The proportion of children with mtDNA depletion was not significantly different between the two prophylactic regimens. Poisson regressions showed that LPV/r and 3TC were associated with mtDNA depletion (reference: control group; LPV/r: PR = 1.75 (CI95%: 1.15-2.68), p < 0.01; 3TC: PR = 1.54 (CI95%: 1.00-2.37), p = 0.05). Moreover, the proportion of children with MDD was unexpectedly high before randomisation in both groups. Long-term health impacts of these mitochondrial DNA parameters should be investigated further for both CHEU and HIV-infected children receiving LPV/r- or 3TC- based regimens.

Longitudinal adherence to maternal antiretroviral therapy and infant Nevirapine prophylaxis from 6 weeks to 18 months postpartum amongst a cohort of mothers and infants in South Africa.

BACKGROUND: Despite improved policies to prevent mother-to-child HIV transmission (MTCT), adherence to maternal antiretroviral therapy (ART) and infant Nevirapine prophylaxis (NVP) is low in South Africa. We describe ART adherence amongst a cohort of HIV-positive mothers and HIV-exposed but uninfected infants from 6 weeks until 18 months post-delivery and identify risk factors for nonadherence. METHODS: Data were collected in 2012-2014 through a nationally representative survey of PMTCT effectiveness. Mother-infant pairs were enrolled during the infant's first immunization visit at 6 weeks. Mothers and HIV-exposed infants (2811 pairs) were followed to 18 months at 3-month intervals. Mothers who self-reported being on ART at 6 weeks postpartum (N = 1572 (55.9%)) and infants on NVP at 6 weeks (N = 2370 (84.3%)) were eligible for this analysis and information about their adherence was captured at each interview they attended thereafter. We defined nonadherence within each 3-month interval as self-report of missing > 5% of daily ART/NVP doses, estimated adherence using a Cox survival curve with Andersen & Gill setup for recurring events, and identified risk factors for nonadherence with an extended Cox regression model (separately for mothers and infants) in Stata 13. Results are not nationally representative as this is a subgroup analysis of the follow-up cohort. RESULTS: Amongst mothers on ART at 6 weeks postpartum, cumulative adherence to maternal ART until 18 months was 63.4%. Among infants on NPV at 6 weeks postpartum, adherence to NVP was 74.5%.. Risk factors for nonadherence to maternal ART, controlling for other factors, included mother's age (16-24 years vs. ≥34 years, adjusted Hazard Ratio (aHR): 1.9, 95% CI: 1.4-2.5), nondisclosure of HIV status to anyone (nondisclosure vs. disclosure: aHR: 1.7, 95% CI: 1.3-2.1), and timing of ART initiation (initiated ART after delivery vs. initiated ART before delivery: aHR: 1.6, 95% CI: 1.3-2.0). Provincial variation was seen in nonadherence to infant NVP, controlling for other factors. CONCLUSION: Maintaining ART adherence until 18 months postpartum remains a crucial challenge, with maternal ART adherence among the six week maternal ART cohort below 65% and infant NVP adherence among breastfeeding infants in this cohort below 75%.This is gravely concerning, given the global policy shift to lifelong ART amongst pregnant and lactating women, and the need for extended infant prophylaxis amongst mothers who are not virally suppressed. Our findings suggest that young mothers and mothers who do not disclose their status should be targeted with messages to improve adherence, and that late maternal ART initiation (after delivery) increases the risk of maternal nonadherence.

Factors associated with non-attendance at scheduled infant follow-up visits in an observational cohort of HIV-exposed infants in South Africa, 2012-2014.

BACKGROUND: Since 2001 the South African guidelines to improve child health and prevent vertical HIV transmission recommended frequent infant follow-up with HIV testing at 18 months postpartum. We sought to understand non-attendance at scheduled follow-up study visits up to 18 months, and for the 18-month infant HIV test amongst a nationally representative sample of HIV exposed uninfected (HEU) infants from a high HIV-prevalence African setting. METHODS: Secondary analysis of data drawn from a nationally representative observational cohort study (conducted during October 2012 to September 2014) of HEU infants and their primary caregivers was undertaken. Participants were eligible (N = 2650) if they were 4-8 weeks old and HEU at enrolment. All enrolled infants were followed up every 3 months up to 18 months. Each follow-up visit was scheduled to coincide with each child's routine health visit, where possible. The denominator at each time point comprised HEU infants who were alive and HIV-free at the previous visit. We assessed baseline maternal and early HIV care characteristics associated with the frequency of 'Missed visits' (MV-frequency), using a negative binomial regression model adjusting for the follow-up time in the study, and associated with missed visits at 18 months (18-month MV) using a logistic regression model. RESULTS: The proportion of eligible infants with MV was lowest at 3 months (32.7%) and 18 months (31.0%) and highest at 12 months (37.6%). HIV-positive mothers not on triple antiretroviral therapy (ART) by 6-weeks postpartum had a significantly increased occurrence rate of 'MV-frequency' (adjusted incidence rate ratio, 1.2 (95% confidence interval (CI), 1.1-1.4), p < 0.0001). Compared to those mothers with ART, these mothers also increased the risk of '18-month-MV' (adjusted odds ratio, 1.3 (CI, 1.1-1.6), p = 0.006). Unknown infant nevirapine-intake status increased the rate of 'MV-frequency' (p = 0.02). Mothers > 24 years had a significantly reduced rate of 'MV-frequency' (p ≤ 0.01) and risk of '18-month-MV' (p < 0.01) compared to younger women. Shorter travel time to health facility lowered the occurrence of 'MV-frequency' (p ≤ 0.004). CONCLUSION: Late initiation of maternal ART and infant prophylaxis under the Option- A policy and extended travel time to clinics (measured at 6 weeks postpartum), contributed to higher postnatal MV rates. Mothers older than 24 years had lower MV rates. Targeted interventions may be needed during the current PMTCT Option B+ (lifelong ART to pregnant and lactating women at HIV diagnosis) to circumvent these risk factors and reduce missed visits during HIV-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.

Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4-8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011-12 and 2012-13.

BACKGROUND: South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts. METHODS: Three nationally representative surveys were conducted in 2010, 2011-12 and 2012-13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4-8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3. RESULTS: Overall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45-58%]) of HIV PCR positive infants, 37% (95% CI [28-47%]) in 2010, 64% (95% CI [53-74%]) in 2011 and 63% (95% CI [47-77%]) in 2012 (p < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance. CONCLUSIONS: These data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years.

Infrastructural and human-resource factors associated with return of infant HIV test results to caregivers: secondary analysis of a nationally representative situational assessment, South Africa, 2010.

BACKGROUND: In June 2015, South Africa introduced early infant HIV diagnosis (EID) at birth and ten weeks postpartum. Guidelines recommended return of birth results within a week and ten weeks postpartum results within four weeks. Task shifting was also suggested to increase service coverage. This study aimed to understand factors affecting return of EID results to caregivers. METHODS: Secondary analysis of data gathered from 571 public-sector primary health care facilities (PHCs) during a nationally representative situational assessment, was conducted. The assessment was performed one to three months prior to facility involvement in the 2010 evaluation of the South African programme to prevent mother-to-child HIV transmission (SAPMTCTE). Self-reported infrastructural and human resource EID-related data were collected from managers and designated staff using a structured questionnaire. The main outcome variable was 'EID turn-around-time (TAT) to caregiver' (caregiver TAT), measured as reported number of weeks from infant blood draw to caregiver receipt of results. This was dichotomized as either short (≤3 weeks) or delayed (> 3 weeks) caregiver TAT. Logit-based risk difference analysis was used to assess factors associated with short caregiver TAT. Analysis included TAT to facility (facility TAT), defined as reported number of weeks from infant blood draw to facility receipt of results. RESULTS: Overall, 26.3% of the 571 PHCs reported short caregiver TAT. In adjusted analyses, short caregiver TAT was less achieved when facility TAT was > 7 days (versus ≤7 days) (adjusted risk difference (aRD): - 0.2 (95% confidence interval - 0.3-(- 0.1)), p = 0.006 for 8-14 days and - 0.3 (- 0.5-(- 0.1)), p = 0.006 for > 14 days), and in facilities with staff nurses (compared to those without) (aRD: - 9.4 (- 16.6-(- 2.2), p = 0.011). CONCLUSION: Although short caregiver TAT for EID was only reported in approximately 26% of facilities, these facilities demonstrate that achieving EID TAT of ≤3 weeks is possible, making timely ART initiation within 3 weeks of diagnosis feasible within the public health sector. Our adjusted analyses underpin the need for quick return of results to facilities. They also raise questions around staff mentoring: we hypothesise that facilities with staff nurses were likely to have fewer professional nurses, and thus inadequate senior support.

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.

Brief Report: Selection of HIV-1 Variants With Higher Transmission Potential by 1% Tenofovir Gel Microbicide.

BACKGROUND: Women in the CAPRISA 004 trial assigned to use 1% tenofovir (TFV) microbicide gel, who became HIV-1 infected, had higher viral load set-point and slower antibody avidity maturation compared with placebo participants. We investigated whether TFV gel was selected for viruses with altered genetic characteristics. SETTING: The participants of the CAPRISA 004 trial (n = 28 TFV and 43 placebo) were from KwaZulu-Natal Province, South Africa and were infected with HIV-1 subtype C. After HIV-1 diagnosis, they were recruited into the CAPRISA 002 cohort. METHODS: We analyzed gag sequences from the earliest time point post infection (within 3 months of estimated time of infection). Transmission index was measured using a model which predicts the likelihood of an amino acid to be transmitted. Phylogenetic distance from a regional consensus sequence was calculated from a maximum likelihood phylogenetic tree. RESULTS: Transmission index and distance from the most common (consensus) sequence have been shown to be markers of transmission fitness. We found that viruses infecting TFV gel recipients were closer to the consensus sequence of regional strains (P = 0.003) and had higher transmission index (P = 0.01). The transmission index was weakly correlated with concomitant viral load (Spearman r = 0.22, P = 0.06). CONCLUSION: Decreased acquisition risk may have increased the barrier to infection therefore selecting for fitter, more consensus-like viruses. Such virus fitness effects will need to be considered for future pre-exposure prophylaxis and vaccine trials.

Wealth-related inequality in early uptake of HIV testing among pregnant women: an analysis of data from a national cross-sectional survey, South Africa.

OBJECTIVES: Wealth-related inequality across the South African antenatal HIV care cascade has not been considered in detail as a potential hindrance to eliminating mother-to-child HIV transmission (EMTCT). We aimed to measure wealth-related inequality in early (before enrolling into antenatal care) uptake of HIV testing and identify the contributing determinants. DESIGN: Cross-sectional survey. SETTINGS: South African primary public health facilities in 2012. PARTICIPANTS: A national-level sample of 8618 pregnant women. OUTCOME MEASURES: Wealth-related inequality in early uptake of HIV testing was measured using the Erreygers concentration index (CI) further adjusted for inequality introduced by predicted healthcare need (ie, need-standardised). Determinants contributing to the observed inequality were identified using the Erreygers and Wagstaff decomposition methods. RESULTS: Participants were aged 13 to 49 years. Antenatal HIV prevalence was 33.2%, of which 43.7% came from the lowest 40% wealth group. A pro-poor wealth-related inequality in early HIV testing was observed. The need-standardised concentration index was -0.030 (95% confidence interval -0.038 to -0.022). The proportion of early HIV testing was significantly better in the lower 40% wealth group compared with the higher 40% wealth group (p value=0.040). The largest contributions to the observed inequality were from underlying inequalities in province (contribution, 65.27%), age (-44.38%), wealth group (24.73%) and transport means (21.61%). CONCLUSIONS: Our results on better early uptake of HIV testing among the poorer subpopulation compared with the richer highlights inequity in uptake of HIV testing in South Africa. This socioeconomic difference could contribute to fast-tracking EMTCT given the high HIV prevalence among the lower wealth group. The high contribution of provinces and age to inequality highlights the need to shift from reliance on national-level estimates alone but identify subregional-specific and age-specific bottlenecks. Future interventions need to be context specific and tailored for specific subpopulations and subregional settings.

Uptake and predictors of early postnatal follow-up care amongst mother-baby pairs in South Africa: Results from three population-based surveys, 2010-2013.

BACKGROUND: Achieving World Health Organization (WHO) recommendations for postnatal care (PNC) within the first few weeks of life is vital to eliminating early mother-to-child transmission of HIV (MTCT) and improving infant health. Almost half of the annual global deaths among children under five occur during the first six weeks of life. This study aims to identify uptake of three PNC visits within the first six weeks of life as recommended by WHO among South African mother-infant pairs, and factors associated with uptake. METHODS: We analyzed data from three facility-based, nationally representative surveys (2010, 2011/12 and 2012/13) primarily designed to determine the effectiveness of the South African program to prevent MTCT. This analysis describes the proportion of infants achieving the WHO recommendation of at least 3 PNC visits. Interviews from 27 699 HIV-negative and HIV-positive mothers of infants aged 4-8 weeks receiving their six week immunization were included in analysis. Data were analyzed using STATA 13.0 and weighted for sample ascertainment and South African live births. We fitted a multivariable logistic regression model to estimate factors associated with early PNC uptake. RESULTS: Over half (59.6%, 95% confidence interval (CI) = 59.0-60.3) of mother-infant pairs received the recommended three PNC visits during the first 6 weeks; uptake was 63.1% (95% CI = 61.9-64.3) amongst HIV exposed infants and 58.1% (95% CI = 57.3-58.9) amongst HIV unexposed infants. Uptake of early PNC improved significantly with each survey, but varied significantly by province. Multivariable analysis of the pooled data, controlling for survey year, demonstrated that number of antenatal visits (4+ vs <4 Adjusted odds ratio (aOR) = 1.13, 95% CI = 1.04-1.23), timing of initial antenatal visits (≤12 weeks vs >12 weeks, aOR = 1.13, 95% CI = 1.04-1.23), place of delivery (clinic vs hospital aOR = 1.5, 1.3-1.6), and infant HIV exposure (exposed vs unexposed aOR = 1.2, 95% CI = 1.1-1.2) were the key factors associated with receiving recommended PNC visits. CONCLUSIONS: Approximately 40% of neonates did not receive three or more postnatal care visits in the first 6 weeks of life from 2010-2013. To improve uptake of early PNC, early antenatal booking, more frequent antenatal care attendance, and attention to HIV negative women is needed.

Does adjusting for recall in trend analysis affect coverage estimates for maternal and child health indicators? An analysis of DHS and MICS survey data.

BACKGROUND: The Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) are the major data sources in low- and middle-income countries (LMICs) for evaluating health service coverage. For certain maternal and child health (MCH) indicators, the two surveys use different recall periods: 5 years for DHS and 2 years for MICS. OBJECTIVE: We explored whether the different recall periods for DHS and MICS affect coverage trend analyses as well as missing data and coverage estimates. DESIGNS: We estimated coverage, using proportions with 95% confidence intervals, for four MCH indicators: intermittent preventive treatment of malaria in pregnancy, tetanus vaccination, early breastfeeding and postnatal care. Trends in coverage were compared using data from 1) standard 5-year DHS and 2-year MICS recall periods (unmatched) and 2) DHS restricted to 2-year recall to match the MICS 2-year recall periods (matched). Linear regression was used to explore the relationship between length of recall, missing data and coverage estimates. RESULTS: Differences in coverage trends were observed between matched and unmatched data in 7 of 18 (39%) comparisons performed. The differences were in the direction of the trend over time, the slope of the coverage change or the significance levels. Consistent trends were seen in 11 of the 18 (61%) comparisons. Proportion of missing data was inversely associated with coverage estimates in both short (2 years) and longer (5 years) recall of the DHS (r=-0.3, p=0.02 and r=-0.4, p=0.004, respectively). The amount of missing information was increased for longer recall compared with shorter recall for all indicators (significant odds ratios ranging between 1.44 and 7.43). CONCLUSIONS: In a context where most LMICs are dependent on population-based household surveys to derive coverage estimates, users of these types of data need to ensure that variability in recall periods and the proportion of missing data across data sources are appropriately accounted for when trend analyses are conducted.