An Examination of SARS-CoV-2 Transmission Based on Classroom Distancing in Schools With Other Preventive Measures in Place-Missouri, January-March 2021.

OBJECTIVES: Classroom layout plays a central role in maintaining physical distancing as part of a multicomponent prevention strategy for safe in-person learning during the COVID-19 pandemic. We conducted a school investigation to assess layouts and physical distancing in classroom settings with and without in-school SARS-CoV-2 transmission. METHODS: We assessed, measured, and mapped 90 K-12 (kindergarten through grade 12) classrooms in 3 Missouri public school districts during January-March 2021, prior to widespread prevalence of the Delta variant; distances between students, teachers, and people with COVID-19 and their contacts were analyzed. We used whole-genome sequencing to further evaluate potential transmission events. RESULTS: The investigation evaluated the classrooms of 34 students and staff members who were potentially infectious with COVID-19 in a classroom. Of 42 close contacts (15 tested) who sat within 3 ft of possibly infectious people, 1 (2%) probable transmission event occurred (from a symptomatic student with a longer exposure period [5 days]); of 122 contacts (23 tested) who sat more than 3 ft away from possibly infectious people with shorter exposure periods, no transmission events occurred. CONCLUSIONS: Reduced student physical distancing is one component of mitigation strategies that can allow for increased classroom capacity and support in-person learning. In the pre-Delta variant period, limited physical distancing (<6 ft) among students in K-12 schools was not associated with increased SARS-CoV-2 transmission.

Evaluation of Test to Stay Strategy on Secondary and Tertiary Transmission of SARS-CoV-2 in K-12 Schools - Lake County, Illinois, August 9-October 29, 2021.

The COVID-19 pandemic has resulted in school closures and reduction of in-person learning (1). In August 2021, the Lake County Health Department (LCHD) in Illinois introduced a Test to Stay (TTS) strategy, whereby unvaccinated students, teachers, and staff members with certain school-related COVID-19 exposures could remain in school and participate in school-related extracurricular activities. Eligibility to participate in TTS required the following conditions to be met: 1) the exposure occurred while both the person with COVID-19 (index patient) and the close contact were masked; 2) the close contact remained asymptomatic, practiced consistent mask wearing, and maintained physical distancing; and 3) the close contact underwent testing for SARS-CoV-2 (the virus that causes COVID-19) on days 1, 3, 5, and 7 after exposure to the index patient. LCHD permitted kindergarten through grade 12 (K-12) schools in Lake County to implement TTS; 90 schools, representing 31 school districts in Lake County, implemented TTS during August 9-October 29, 2021. During the implementation period, 258 COVID-19 cases were reported. Among 1,035 students and staff members enrolled in TTS, the secondary attack risk (number of close contacts who received a positive SARS-CoV-2 test result within 14 days after exposure to an index patient, divided by total number of close contacts) was 1.5% (16 of 1,035). Among the 16 secondary cases identified, all were in students, and none appeared to transmit SARS-CoV-2 to other school-based contacts. However, nine tertiary cases were identified among household contacts of the 16 secondary cases, and four of the nine were fully vaccinated. Assuming a maximum of 8 missed school days for every 10-day quarantine period, up to 8,152 in-person learning days were saved among TTS participants. Implementation of TTS with other concurrent prevention strategies, including masking and physical distancing, limited further spread of SARS-CoV-2 within K-12 schools and allowed students to safely sustain in-person learning. Although vaccination remains the leading public health recommendation to protect against COVID-19 for those aged ≥5 years, schools might consider TTS as an option for allowing close contacts who are not fully vaccinated to remain in the classroom as an alternative to home quarantine.

Use of Stay-at-Home Orders and Mask Mandates to Control COVID-19 Transmission - Blackfeet Tribal Reservation, Montana, June-December 2020.

COVID-19 has disproportionately affected persons who identify as non-Hispanic American Indian or Alaska Native (AI/AN) (1). The Blackfeet Tribal Reservation, the northern Montana home of the sovereign Blackfeet Nation, with an estimated population of 10,629 (2), detected the first COVID-19 case in the community on June 16, 2020. Following CDC guidance,* and with free testing widely available, the Indian Health Service and Blackfeet Tribal Health Department began investigating all confirmed cases and their contacts on June 25. The relationship between three community mitigation resolutions passed and enforced by the Blackfeet Tribal Business Council and changes in the daily COVID-19 incidence and in the distributions of new cases was assessed. After the September 28 issuance of a strictly enforced stay-at-home order and adoption of a mask use resolution, COVID-19 incidence in the Blackfeet Tribal Reservation decreased by a factor of 33 from its peak of 6.40 cases per 1,000 residents per day on October 5 to 0.19 on November 7. Other mitigation measures the Blackfeet Tribal Reservation used included closing the east gate of Glacier National Park for the summer tourism season, instituting remote learning for public school students throughout the fall semester, and providing a Thanksgiving meal to every household to reduce trips to grocery stores. CDC has recommended use of routine public health interventions for infectious diseases, including case investigation with prompt isolation, contact tracing, and immediate quarantine after exposure to prevent and control transmission of SARS-CoV-2, the virus that causes COVID-19 (3). Stay-at-home orders, physical distancing, and mask wearing indoors, outdoors when physical distancing is not possible, or when in close contact with infected or exposed persons are also recommended as nonpharmaceutical community mitigation measures (3,4). Implementation and strict enforcement of stay-at-home orders and a mask use mandate likely helped reduce the spread of COVID-19 in the Blackfeet Tribal Reservation.

National-level effectiveness of ART to prevent early mother to child transmission of HIV in Namibia.

BACKGROUND: Namibia introduced the prevention of mother to child HIV transmission (MTCT) program in 2002 and lifelong antiretroviral therapy (ART) for pregnant women (option B-plus) in 2013. We sought to quantify MTCT measured at 4-12 weeks post-delivery. METHODS: During Aug 2014-Feb 2015, we recruited a nationally representative sample of 1040 pairs of mother and infant aged 4-12 weeks at routine immunizations in 60 public health clinics using two stage sampling approach. Of these, 864 HIV exposed infants had DNA-PCR HIV test results available. We defined an HIV exposed infant if born to an HIV-positive mother with documented status or diagnosed at enrollment using rapid HIV tests. Dried Blood Spots samples from HIV exposed infants were tested for HIV. Interview data and laboratory results were collected on smartphones and uploaded to a central database. We measured MTCT prevalence at 4-12 weeks post-delivery and evaluated associations between infant HIV infection and maternal and infant characteristics including maternal treatment and infant prophylaxis. All statistical analyses accounted for the survey design. RESULTS: Based on the 864 HIV exposed infants with test results available, nationally weighted early MTCT measured at 4-12 weeks post-delivery was 1.74% (95% confidence interval (CI): 1.00%-3.01%). Overall, 62% of mothers started ART pre-conception, 33.6% during pregnancy, 1.2% post-delivery and 3.2% never received ART. Mothers who started ART before pregnancy and during pregnancy had low MTCT prevalence, 0.78% (95% CI: 0.31%-1.96%) and 0.98% (95% CI: 0.33%-2.91%), respectively. MTCT rose to 4.13% (95% CI: 0.54%-25.68%) when the mother started ART after delivery and to 11.62% (95% CI: 4.07%-28.96%) when she never received ART. The lowest MTCT of 0.76% (95% CI: 0.36% - 1.61%) was achieved when mother received ART and ARV prophylaxis within 72hrs for infant and highest 22.32% (95%CI: 2.78% -74.25%) when neither mother nor infant received ARVs. After adjusting for mother's age, maternal ART (Prevalence Ratio (PR) = 0.10, 95% CI: 0.03-0.29) and infant ARV prophylaxis (PR = 0.32, 95% CI: 0.10-0.998) remained strong predictors of HIV transmission. CONCLUSION: As of 2015, Namibia achieved MTCT of 1.74%, measured at 4-12 weeks post-delivery. Women already on ART pre-conception had the lowest prevalence of MTCT emphasizing the importance of early HIV diagnosis and treatment initiation before pregnancy. Studies are needed to measure MTCT and maternal HIV seroconversion during breastfeeding.

Declines in SARS-CoV-2 Transmission, Hospitalizations, and Mortality After Implementation of Mitigation Measures- Delaware, March-June 2020.

Mitigation measures, including stay-at-home orders and public mask wearing, together with routine public health interventions such as case investigation with contact tracing and immediate self-quarantine after exposure, are recommended to prevent and control the transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1-3). On March 11, the first COVID-19 case in Delaware was reported to the Delaware Division of Public Health (DPH). The state responded to ongoing community transmission with investigation of all identified cases (commencing March 11), issuance of statewide stay-at-home orders (March 24-June 1), a statewide public mask mandate (from April 28), and contact tracing (starting May 12). The relationship among implementation of mitigation strategies, case investigations, and contact tracing and COVID-19 incidence and associated hospitalization and mortality was examined during March-June 2020. Incidence declined by 82%, hospitalization by 88%, and mortality by 100% from late April to June 2020, as the mask mandate and contact tracing were added to case investigations and the stay-at-home order. Among 9,762 laboratory-confirmed COVID-19 cases reported during March 11-June 25, 2020, two thirds (6,527; 67%) of patients were interviewed, and 5,823 (60%) reported completing isolation. Among 2,834 contacts reported, 882 (31%) were interviewed and among these contacts, 721 (82%) reported completing quarantine. Implementation of mitigation measures, including mandated mask use coupled with public health interventions, was followed by reductions in COVID-19 incidence and associated hospitalizations and mortality. The combination of state-mandated community mitigation efforts and routine public health interventions can reduce the occurrence of new COVID-19 cases, hospitalizations, and deaths.

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.

HIV-exposed uninfected infant morbidity and mortality within a nationally representative prospective cohort of mother-infant pairs in Zimbabwe.

OBJECTIVE: To examine morbidity and mortality risk among HIV-exposed uninfected (HEU) infants. DESIGN: Secondary data analysis of HEU infants in a prospective cohort study of mother-infant pairs. METHODS: Infants were recruited from immunization clinics (n = 151) in Zimbabwe from February to August 2013, enrolled at 4-12 weeks age, and followed every 3 months until incident HIV-infection, death, or 18-month follow-up. We estimated cumulative mortality probability and hazard ratios with 95% confidence intervals (CIs) using Kaplan-Meier curves and Cox regression, respectively. We also described reported reasons for infant hospitalization and symptoms preceding death. Median weight-for-age z-scores (WAZ) and median age were calculated and analyzed across study visits. RESULTS: Of 1188 HIV-exposed infants, 73 (6.1%) contracted HIV; we analyzed the remaining 1115 HEU infants. In total, 54 (4.8%) infants died, with median time to death of 5.5 months since birth (interquartile range: 3.6-9.8 months). Diarrhea, difficulty breathing, not eating, fever, and cough were commonly reported (range: 7.4-22.2%) as symptoms preceding infant death. Low birth weight was associated with higher mortality (adjusted hazard ratio 2.66, CI: 1.35-5.25), whereas maternal antiretroviral therapy predelivery (adjusted hazard ratio 0.34, CI: 0.18-0.64) and exclusive breastfeeding (adjusted hazard ratio 0.50, CI: 0.28-0.91) were associated with lower mortality. Overall, 9.6% of infants were hospitalized. Infant median WAZ declined after 3 months of age, reaching a minimum at 14.5 months of age, at which 50% of infants were underweight (WAZ below -2.0). CONCLUSION: Clinical interventions including maternal antiretroviral therapy; breastfeeding and infant feeding counseling and support; and early prevention, identification, and management of childhood illness; are needed to reduce HEU infant morbidity and mortality.

Mother-To-Child Transmission of HIV in Adolescents and Young Women: Findings From a National Prospective Cohort Survey, Zimbabwe, 2013-2014.

PURPOSE: We assessed 18-month cumulative mother-to-child HIV transmission (MTCT) risk and risk factors for no antiretroviral medication use during pregnancy among adolescent, young women, and adult mothers in Zimbabwe. METHODS: We analyzed data from a prospective survey of 1,171 mother-infant pairs with HIV-exposed infants aged 4-12 weeks who were recruited from 151 immunization clinics from February to August 2013. HIV-exposed infants were followed until diagnosed with HIV, death, or age 18 months. Findings were weighted and adjusted for complex survey design and nonresponse. RESULTS: The 18-month cumulative MTCT risk was highest among adolescent aged ≤19 years (12%) followed by young women aged 20-24 years (7.5%) and adult women aged ≥25 years (6.9%). Across these groups, more than 94% had ≥1 antenatal care visit by 21 weeks of gestation, more than 95% had ≥1 HIV test, and more than 98% knew their HIV status. Of known HIV-positive mothers, maternal antiretroviral medication coverage during pregnancy was 76.8% (95% confidence interval: 65.1-85.5), 83.8% (78.6-87.9), and 87.8% (84.6-90.4) among adolescent, young women, and adult mothers, respectively. Among HIV-positive mothers diagnosed prenatally, the adjusted odds ratio of no ARV use during pregnancy was increased among those who had no antenatal care attendance (adjusted odds ratio: 7.7 [3.7-16.0]), no HIV testing (7.3 [2.3-23.5]), no prepartum CD4 count testing (2.1 [1.3-3.4]), and maternal HIV identification during pregnancy (2.9 [1.8-4.8]). Age was not a risk factor. CONCLUSIONS: With similar coverage of prevention of MTCT services, the 18-month cumulative MTCT risk was higher among adolescents and young women, compared with adults. Additional research should examine the causes to develop targeted interventions.

Status of HIV Case-Based Surveillance Implementation - 39 U.S. PEPFAR-Supported Countries, May-July 2019.

Human immunodeficiency virus (HIV) case-based surveillance (CBS) systematically and continuously collects available demographic and health event data (sentinel events*) about persons with HIV infection from diagnosis and, if available, throughout routine clinical care until death, to characterize HIV epidemics and guide program improvement (1,2). Surveillance signals such as high viral load, mortality, or recent HIV infection can be used for rapid public health action. To date, few standardized assessments have been conducted to describe HIV CBS systems globally (3,4). For this assessment, a survey was disseminated during May-July 2019 to all U.S. President's Emergency Plan for AIDS Relief (PEPFAR)-supported countries with CDC presence† (46) to describe CBS implementation and identify facilitators and barriers. Among the 39 (85%) countries that responded,§ 20 (51%) have implemented CBS, 15 (38%) were planning implementation, and four (10%)¶ had no plans for implementation. All countries with CBS reported capturing information at the point of diagnosis, and 85% captured sentinel event data. The most common characteristic (75% of implementation countries) that facilitated implementation was using a health information system for CBS. Barriers to CBS implementation included lack of country policies/guidance on mandated reporting of HIV and on CBS, lack of unique identifiers to match and deduplicate patient-level data, and lack of data security standards. Although most surveyed countries reported implementing or planning for implementation of CBS, these barriers need to be addressed to implement effective HIV CBS that can inform the national response to the HIV epidemic.

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.

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

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

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.

Uptake of care and treatment amongst a national cohort of HIV positive infants diagnosed at primary care level, South Africa.

BACKGROUND: Loss to follow-up after a positive infant HIV diagnosis negates the potential benefits of robust policies recommending immediate triple antiretroviral therapy initiation in HIV positive infants. Whilst the diagnosis and follow-up of HIV positive infants in urban, specialized settings is easier to institutionalize, there is little information about access to care amongst HIV positive children diagnosed at primary health care clinic level. We sought to understand the characteristics of HIV positive children diagnosed with HIV infection at primary health care level, across all provinces of South Africa, their attendance at study-specific exit interviews and their reported uptake of HIV-related care. The latter could serve as a marker of knowledge, access or disclosure. METHODS: Secondary analysis of data gathered about HIV positive children, participating in an HIV-exposed infant national observational cohort study between October 2012 and September 2014, was undertaken. HIV infected children were identified by total nucleic acid polymerase chain reaction using standardized procedures in a nationally accredited central laboratory. Descriptive analyses were conducted on the HIV positive infant population, who were treated as a case series in this analysis. Data from interviews conducted at baseline (six-weeks post-delivery) and on study exit (the first visit following infant HIV positive diagnosis) were analysed. RESULTS: Of the 2878 HIV exposed infants identified at 6 weeks, 1803 (62.2%), 1709, 1673, 1660, 1680 and 1794 were see at 3, 6, 9, 12, 15 and 18 months respectively. In total, 101 tested HIV positive (67 at 6 weeks, and 34 postnatally). Most (76%) HIV positive infants were born to single mothers with a mean age of 26 years and an education level above grade 7 (76%). Although only 33.7% of pregnancies were planned, 83% of mothers reported receiving antiretroviral drugs to prevent MTCT. Of the 44 mothers with a documented recent CD4 cell count, the median was 346.8 cell/mm3. Four mothers (4.0%) self-reported having had TB. Only 59 (58.4%) HIV positive infants returned for an exit interview after their HIV diagnosis; there were no statistically significant differences in baseline characteristics between HIV positive infants who returned for an exit interview and those who did not. Amongst HIV positive infants who returned for an exit interview, only two HIV positive infants (3.4%) were reportedly receiving triple antiretroviral therapy (ART). If we assume that all HIV positive children who did not return for their exit interview received ART, then ART uptake amongst these HIV positive children < 18 months would be 43.6%. CONCLUSIONS: Early ART uptake amongst children aged 15 months and below was low. This raises questions about timely, early paediatric ART uptake amongst HIV positive children diagnosed in primary health care settings. Qualitative work is needed to understand low and delayed paediatric ART uptake in young children, and more work is needed to measure progress with infant ART initiation at primary care level since 2014.

Impact of Timing of Antiretroviral Treatment and Birth Weight on Mother-to-Child Human Immunodeficiency Virus Transmission: Findings From an 18-Month Prospective Cohort of a Nationally Representative Sample of Mother-Infant Pairs During the Transition From Option A to Option B+ in Zimbabwe.

Background: Preventing mother-to-child transmission of human immunodeficiency virus transmission (MTCT) depends on early initiation of antiretroviral therapy (ART). We report the 18-month MTCT risk during the transition from Option A to Option B+ in Zimbabwe, and assess whether ART preconception could eliminate MTCT in breastfeeding populations. Methods: In 2013, we consecutively recruited a nationally representative sample of 6051 infants aged 4-12 weeks and their mothers from 151 immunization clinics using a multistage stratified cluster sampling method. We identified 1172 human immunodeficiency virus (HIV)-exposed infants and evaluated them at baseline and every 3 months until the child became HIV-infected, died, or reached age 18 months. Results: The cumulative MTCT risk through 18 months postdelivery was 7.0%. Of the HIV-infected mothers, 35.3% started ART preconception, 28.9% during pregnancy, and 9.7% after delivery, and 16.0% received zidovudine during pregnancy. Compared to mothers without antiretroviral drug use, MTCT among those starting ART preconception and during pregnancy was lower by 88% (adjusted hazard ratio [aHR], 0.12; 95% confidence interval [CI], .06-.24) and 75% (aHR, 0.25; 95% CI, .14-.45), respectively. HIV-exposed infants with birth weight <2.5 kg (low birth weight) were 2.6-fold more likely to acquire HIV infection compared to those with birth weight ≥2.5 kg (aHR, 2.57; 95% CI, 1.44-4.59). Controlling for other factors, breastfeeding was not significantly associated with MTCT. Conclusions: ART preconception has the highest impact on reducing MTCT, indicating that HIV-infected, reproductive-age women should be prioritized in "treat-all" strategies. HIV-infected mothers without ART use should be identified at the first immunization visit and treatment initiated to reduce postdelivery MTCT. MTCT risk is higher in mothers with low-birth-weight deliveries.

Mothers' willingness to pay for daughters' HPV vaccine in northern Vietnam.

HPV vaccine is effective in preventing human papillomavirus, the main cause of cervical cancer. In Vietnam, at first, it was subsidized at $5 a dose and reached the coverage of 96% in two pilot provinces, indicating potentially high acceptance. Currently, it is provided at $120-195 for three doses. This is a cross-sectional study, conducted in two northern rural districts of Vietnam. Researchers present findings to show 53.1% of mothers stated their willingness to pay (WTP) for HPV vaccine for their daughters. Perceptions on cost and condom use were associated with WTP. Mothers' affordability ranged from under $23 to $46. Measures should be implemented soon to make HPV vaccine more affordable.

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

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

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

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

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.