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.

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.

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.

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.

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.

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.

Evidence of pervasive biologically functional secondary structures within the genomes of eukaryotic single-stranded DNA viruses.

Single-stranded DNA (ssDNA) viruses have genomes that are potentially capable of forming complex secondary structures through Watson-Crick base pairing between their constituent nucleotides. A few of the structural elements formed by such base pairings are, in fact, known to have important functions during the replication of many ssDNA viruses. Unknown, however, are (i) whether numerous additional ssDNA virus genomic structural elements predicted to exist by computational DNA folding methods actually exist and (ii) whether those structures that do exist have any biological relevance. We therefore computationally inferred lists of the most evolutionarily conserved structures within a diverse selection of animal- and plant-infecting ssDNA viruses drawn from the families Circoviridae, Anelloviridae, Parvoviridae, Nanoviridae, and Geminiviridae and analyzed these for evidence of natural selection favoring the maintenance of these structures. While we find evidence that is consistent with purifying selection being stronger at nucleotide sites that are predicted to be base paired than at sites predicted to be unpaired, we also find strong associations between sites that are predicted to pair with one another and site pairs that are apparently coevolving in a complementary fashion. Collectively, these results indicate that natural selection actively preserves much of the pervasive secondary structure that is evident within eukaryote-infecting ssDNA virus genomes and, therefore, that much of this structure is biologically functional. Lastly, we provide examples of various highly conserved but completely uncharacterized structural elements that likely have important functions within some of the ssDNA virus genomes analyzed here.