Enhanced peer-group strategies to support the prevention of mother-to-child HIV transmission leads to increased retention in care in Uganda: A randomized controlled trial.

INTRODUCTION: Despite the scale-up of Option B+, long-term retention of women in HIV care during pregnancy and the postpartum period remains an important challenge. We compared adherence to clinic appointments and antiretroviral therapy (ART) at 6 weeks, 6, and and 24 months postpartum among pregnant women living with HIV and initiating Option B+. Women were randomized to a peer group support, community-based drug distribution and income-generating intervention called "Friends for Life Circles" (FLCs) versus the standard of care (SOC). Our secondary outcome was infant HIV status and HIV-free survival at 6 weeks and 18 months postpartum. METHODS: Between 16 May 2016 and 12 September 2017, 540 ART-naïve pregnant women living with HIV at urban and rural health facilities in Uganda were enrolled in the study at any gestational age. Participants were randomized 1:1 to the unblinded FLC intervention or SOC at enrolment and assessed for adherence to the prevention of mother-to-child HIV transmission (PMTCT) clinic appointments at 6 weeks, 12, and 24 months postpartum, self-reported adherence to ART at 6 weeks, 6 and 24 months postpartum and supported by plasma HIV-1 RNA viral load (VL) measured at the same time points, retention in care through the end of study, and HIV status and HIV-free survival of infants at 18 months postpartum. The FLC groups were formed during pregnancy within 4 months of enrollment and held monthly meetings in their communites, and were followed up until the last group participant reached 24 months post delivery. We used Log-rank and Chi-Square p-values to test the equality of Kaplan-Meier survival probabilities and hazard rates (HR) for failure to retain in care for any reason by study arm. RESULTS: There was no significant difference in adherence to PMTCT clinic visits or to ART or in median viral loads between FLC and SOC arms at any follow-up time points. Retention in care through the end of study was high in both arms but significantly higher among participants randomized to FLC (86.7%) compared to SOC (79.3%), p = 0.022. The adjusted HR of visit dropout was 2.4 times greater among participants randomized to SOC compared to FLC (aHR = 2.363, 95% CI: 1.199-4.656, p = 0.013). Median VL remained < 400 copies/ml in both arms at 6 weeks, 6, and 24 months postpartum. Eight of the 431 infants tested at 18 months were HIV positive (1.9%), however, this was not statistically different among mothers enrolled in the FLC arm compared to those in the SOC arm. At 18 months, HIV-free survival of children born to mothers in the FLC arm was significantly higher than that of children born to mothers in the SOC arm. CONCLUSIONS: Our findings suggest that programmatic interventions that provide group support, community-based ART distribution, and income-generation activities may contribute to retention in PMTCT care, HIV-free survival of children born to women living with HIV, and ultimately, to the elimination of mother-to-child HIV transmission (EMTCT). TRIAL REGISTRATION: NCT02515370 (04/08/2015) on ClinicalTrials.gov.

'When I receive ARVs through my group, my heart settles': Participants' perceptions and experiences of Friends for Life Circles for Option B+ in Kampala and Mityana Districts, Uganda.

The Friends for Life Circles (FLC) was a parallel randomized controlled trial testing the efficacy of a group peer support intervention to support long-term adherence to Option B+ in Kampala and Mityana districts in Uganda. We explored FLC participants' experiences and perceptions of the intervention on adherence to Option B+ for PMTCT and potential implications for strengthening the PMTCT program. We collected data from six focus group discussions with lactating women enrolled in the FLC intervention, and from 14 key informant interviews with health workers, district and national level stakeholders, as well as male partners of FLC participants. Data were analysed using a content thematic approach in a continuous and iterative process. Women described the FLC intervention as acceptable and beneficial in enhancing their understanding of HIV and the need for ART. The FLC helped women, especially those newly diagnosed with HIV infection to come to terms with their diagnosis and overcome the fear of death linked to testing HIV positive, and provided opportunities to enhance ART initiation, resumption and adherence. The FLC provided safe spaces for women, to learn about ART, and to receive support from peers including adherence reminders through home visits and 'coded' reminder messages. Receiving ART from support groups protected members from stigma and long lines at health facilities. Fear of stigma, health system challenges, the high cost of caring for animals and lack of money to save in groups were key challenges noted. The FLC support groups were crucial in providing needed support for women to initiate, resume and adhere to lifelong ART for Option B+. It is important that women who test HIV positive and start ART for life receive psychosocial support from peers and health workers to improve chances of preventing HIV transmission from mothers to children.

Strengthening capacity of health workers to diagnose birth defects in Ugandan hospitals from 2015 to 2021.

BACKGROUND: Limited diagnostic capabilities, resources and health worker skills have deterred the advancement of birth defects surveillance systems in most low- and middle-income countries (LMICs). Empowering health workers to identify and diagnose major external birth defects (BDs) is crucial to establishing effective hospital-based BD surveillance. Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration BD Surveillance System consists of three diagnostic levels: (1) surveillance midwives, (2) MU-JHU clinical team, and (3) U.S. Centers for Disease Control and Prevention (CDC) birth defects subject matter experts (SMEs) who provide confirmatory diagnosis. The diagnostic concordance of major external BDs by surveillance midwives or MU-JHU clinical team with CDC birth defects SMEs were estimated. METHODS: Study staff went through a series of trainings, including birth defects identification and confirmation, before surveillance activities were implemented. To assess the diagnostic concordance, we analyzed surveillance data from 2015 to 2021 for major external BDs: anencephaly, iniencephaly, encephalocele, spina bifida, craniorachischisis, microcephaly, anophthalmia/microphthalmia, anotia/microtia, cleft palate alone, cleft lip alone, cleft lip with cleft palate, imperforate anus, hypospadias, talipes equinovarus, limb reduction, gastroschisis, and omphalocele. Positive predictive value (PPV) as the proportion of BDs diagnosed by surveillance midwives or MU-JHU clinical team that were confirmed by CDC birth defects SMEs was computed. PPVs between 2015 and 2018 and 2019-2021 were compared to assess the accuracy of case diagnosis over time. RESULTS: Of the 204,332 infants examined during 2015-2021, 870 infants had a BD. Among the 1,245 BDs identified, 1,232 (99.0%) were confirmed by CDC birth defects SMEs. For surveillance midwives, PPV for 7 of 17 BDs was > 80%. For the MU-JHU clinical team, PPV for 13 of 17 BDs was > 80%. Among surveillance midwives, PPV improved significantly from 2015 to 2018 to 2019-2021, for microcephaly (+ 50.0%), cleft lip with cleft palate (+ 17.0%), imperforate anus (+ 30.0%), and talipes equinovarus (+ 10.8%). Improvements in PPV were also observed among MU-JHU clinical team; however, none were significant. CONCLUSION: The diagnostic accuracy of the midwives and clinical team increased, highlighting that BD surveillance, by front-line health care workers (midwives) in LMICs is possible when midwives receive comprehensive training, technical support, funding and continuous professional development.

Enhanced Peer-Group strategies to support prevention of Mother-to-Child HIV transmission leads to increased retention in care in Uganda: A Randomized controlled trial.

Introduction: Despite scale up of Option B+, long-term retention of women in HIV care during pregnancy and the postpartum period remains an important challenge. We compared adherence to clinic appointments and antiretroviral therapy (ART) at different follow-up time points between enrolment and 24 months postpartum among pregnant women living with HIV and initiating Option B+ randomized to a peer group support, community-based drug distribution and income-generating intervention called "Friends for Life Circles" (FLCs) versus the standard of care (SOC). Methods: Between 16 May 2016 and 12 September 2017, 540 ART-naïve pregnant women living with HIV at urban and rural health facilities in Uganda were enrolled in the study. Participants were randomized 1:1 to the FLC intervention or SOC and assessed for adherence to prevention of mother to child HIV transmission (PMTCT) clinic appointments at 6 weeks, 12 and 24 months postpartum, self-reported adherence to ART at 6 weeks, 6 and 24 months postpartum validated by plasma HIV-1 RNA viral load (VL) measured at the same time points, and HIV status and HIV-free survival of infants at 18 months postpartum. We used Log-rank and Chi-Square p-values to test the equality of Kaplan-Meier survival probabilities and hazard rates (HR) for failure to retain in care for any reason by study arm. Results: There was no significant difference in adherence to PMTCT clinic visits or to ART or in median viral loads between FLC and SOC arms at any follow-up time points. Retention in care through the end of study was high in both arms but significantly higher among participants randomized to FLC (86.7%) compared to SOC (79.3%), p=0.022. The adjusted HR of visit dropout was 2.5 times greater among participants randomized to SOC compared to FLC (aHR=2.498, 95% CI: 1.417 - 4.406, p=0.002). Median VL remained < 400 copies/ml in both arms at 6 weeks, 6 and 24 months postpartum. Conclusions: Our findings suggest that programmatic interventions that provide group support, community based ART distribution and income-generation activities may contribute to retention in PMTCT care, HIV-free survival of children born to women living with HIV, and to the elimination of mother to child HIV transmission (MTCT).

Twenty years of Prevention of Mother to Child HIV Transmission: research to implementation at a national referral hospital in Uganda.

Background: Over 90% of new paediatric HIV infections are acquired through mother to child transmission. Prevention of mother to child HIV transmission (PMTCT) research in sub-Saharan Africa informed WHO guidelines which enabled implementation of PMTCT programs globally. Objectives: To describe Makerere University-Johns Hopkins University (MU-JHU) perinatal HIV prevention research and implementation of the Mulago National Referral Hospital (MNRH) PMTCT program. Methods: Perinatal HIV prevention studies conducted at MU-JHU between 1997-2016 were summarized. Program aggregated data was extracted and analyzed using STATA 15. Results: In 1999, the HIVNET 012 study demonstrated that single-dose nevirapine (sdNVP) to the mother at onset of labor and to her newborn, reduced MTCT by nearly 50%. In 2016, the PROMISE study documented the safety and efficacy of ART during pregnancy and breastfeeding period. Program implementation at MNRH started in 2000. Uptake of HIV testing increased from 70% to 99% from 2006 onwards. sd NVP was the initial ARV regimen but by 2012, MOH recommended Option B+(triple therapy). MTCT rates reduced from 16.9% in 2001 to 2.3% in 2020. Conclusion: Perinatal HIV prevention clinical trials conducted at MU-JHU provided evidence to inform WHO PMTCT guidelines. MNRH program evaluation demonstrated the significant decline in MTCT rates over the last two decades.

Mobile tablets for real-time data collection for hospital-based birth defects surveillance in Kampala, Uganda: Lessons learned.

Sustainable birth defects surveillance systems provide countries with estimates of the prevalence of birth defects to guide prevention, care activities, and evaluate interventions. We used free and open-source software (Open Data Kit) to implement an electronic system to collect data for a hospital-based birth defects surveillance system at four major hospitals in Kampala, Uganda. We describe the establishment, successes, challenges, and lessons learned from using mobile tablets to capture data and photographs. After intensive training, surveillance midwives collected data using Android tablets with inbuilt logic checks; another surveillance midwife checked the quality of the data in real-time before data were securely uploaded onto a local server. Paper forms were used when needed as a backup for the electronic system. We experienced several challenges implementing the surveillance system, including forgotten passwords, unstable network, reduced tablet speed and freezing, loss of touch-screen sensitivity, decreased battery strength, and repetitive extensive retraining. We addressed these challenges by backing up and removing all photos from the tablet, uninstalling irrelevant applications to the study to increase storage space and speed, and monitoring and updating the system based mainly on feedback from the midwives. From August 2015 to December 2018, surveillance midwives documented information on 110,752 births at the participating hospitals. Of these, 110,573 (99.8%) were directly entered into the electronic data system and 179 (0.2%) were captured on paper forms. The use of mobile tablets for real-time data collection was successful in a hospital-based birth defects surveillance system in a resource-limited setting. Extensive training and follow-up can overcome challenges and are key to preparing staff for a successful data collection system.

HIV genotypic resistance among pregnant women initiating ART in Uganda: a baseline evaluation of participants in the Option B+ clinical trial.

Background: Pre-treatment HIV drug resistance is a threat to elimination of mother to child HIV transmission and could lead to virological failure among HIV-positive pregnant women. We analysed genotypic HIV drug resistance (HIVDR) of baseline samples of participants enrolled in the Option B+ clinical trial in Uganda. Methods: HIV-infected pregnant women attending antenatal care were enrolled from Uganda's National Referral Hospital (Mulago) and Mityana District general hospital and surrounding health centers (HCs). Genotypic HIV testing was performed on blood samples from the first 135 enrolled women out of a subset of 136 participants (25%) who had a baseline VL>1000 copies/mL as one sample failed to amplify. Results: 159/540 (29.4%) had a VL < 1000 copies/ml and 381/540 (70.6%) had a VL >1,000 copies/ml. Of the women with VL>1000 copies/ml, 32 (23.7%) had resistance mutations including 29/135 (21.5%) NNRTI mutations, 6/135 (4.4%) NRTI mutations and 3/135 (2.2%) had both NNRTI and NRTI mutations. The most common NNRTI resistance mutations were: K103KN (5), K103N (5), V179T (4) and E138A (4). Conclusions: One quarter of the HIV-infected pregnant women in this trial at baseline had NNRTI genotypic resistance mutations. Our findings support new WHO guidelines for first-line ART that were changed to dolutegravir-based regimens.

Prevalence of neural tube defects, maternal HIV status, and antiretroviral therapy from a hospital-based birth defect surveillance in Kampala, Uganda.

BACKGROUND: The estimated prevalence of neural tube defects (NTDs) in Africa is 11.7 per 10,000 live births; however, data on the impact of antiretroviral therapy (ART) during pregnancy and the risk for birth defects in Africa are limited. METHODS: Data from a hospital-based surveillance program at four hospitals in Kampala, Uganda were used to estimate the baseline prevalence of NTDs and assess potential associations with HIV status and ART use. All live births, stillbirths, and spontaneous abortions delivered at the participating hospitals affected with selected birth defects between August 2015 and December 2018 were included. Trained midwives collected data from hospital records, maternal interviews, photographs, and narrative descriptions of birth defects. We estimated NTD prevalence per 10,000 births (live, stillbirths, spontaneous abortions), prevalence ratios, and 95% confidence intervals (CIs). RESULTS: A total of 110,752 births from 107,133 women were included in the analysis; 9,394 (8.8%) women were HIV-infected and among those with HIV infection, 95.6% (n = 8,977) were on ART at delivery. Overall, 109 births were affected with NTDs, giving a prevalence of 9.8 (95% CI [8.2, 11.9]). Spina bifida (n = 63) was the most common type of NTD, with a prevalence of 5.7 (95% CI [4.4, 7.3]), followed by anencephaly (n = 31), with a prevalence of 2.8 (95% CI [2.0, 4.0]). CONCLUSION: The prevalence of NTDs among births in Kampala, Uganda is consistent with current estimates for Africa. With the continued introduction of new medications that may be taken during pregnancy, sustainable birth defect surveillance systems and pharmacovigilance are indicated.

Twenty years of prevention of mother to child HIV transmission: research to implementation at a national referral hospital in Uganda

Background: Over 90% of new paediatric HIV infections are acquired through mother to child transmission. Prevention of mother to child HIV transmission (PMTCT) research in sub-Saharan Africa informed WHO guidelines which enabled implementation of PMTCT programs globally. Objectives: To describe Makerere University-Johns Hopkins University (MU-JHU) perinatal HIV prevention research and implementation of the Mulago National Referral Hospital (MNRH) PMTCT program. Methods: Perinatal HIV prevention studies conducted at MU-JHU between 1997­2016 were summarized. Program aggregated data was extracted and analyzed using STATA 15. Results: In 1999, the HIVNET 012 study demonstrated that single-dose nevirapine (sdNVP) to the mother at onset of labor and to her newborn, reduced MTCT by nearly 50%. In 2016, the PROMISE study documented the safety and efficacy of ART during pregnancy and breastfeeding period. Program implementation at MNRH started in 2000. Uptake of HIV testing increased from 70% to 99% from 2006 onwards. sd NVP was the initial ARV regimen but by 2012, MOH recommended Option B+(triple therapy). MTCT rates reduced from 16.9% in 2001 to 2.3% in 2020. Conclusion: Perinatal HIV prevention clinical trials conducted at MU-JHU provided evidence to inform WHO PMTCT guidelines. MNRH program evaluation demonstrated the significant decline in MTCT rates over the last two decades.

Prevalence of undetectable and suppressed viral load in HIV-infected pregnant women initiating Option B+ in Uganda: an observational study nested within a randomized controlled trial.

BACKGROUND: Viral load (VL) testing is key in monitoring adherence to antiretroviral therapy (ART) and documenting HIV treatment response. As per HIV treatment guidelines in Uganda, the first VL test is recommended 6 months after initiation of ART. Undetectable VL (uVL) at ART initiation may be helpful in detecting elite controllers in the absence of previous ART use. We investigated viral suppression at ART initiation among a cohort of HIV-positive pregnant women enrolled in the Friends for Life Circles (FLC) for Option B+ randomized controlled trial (RCT). METHODS: Pregnant women ≥ 18 years of age testing positive for HIV at their first antenatal care visit and starting on ART Option B+ as per the National PMTCT Program guidelines were enrolled into the FLC for Option B+ RCT in urban Kampala and rural Mityana districts of Uganda. Each participant had whole blood samples collected at enrolment to assess baseline VL. Plasma HIV-1 RNA was quantified using COBAS Ampliprep /COBAS Taqman. Baseline VL below 400 RNA copies/ml was considered as viral suppression while baseline VL below 20 RNA copies/ml was considered uVL. RESULTS: The mean duration from the date of ART initiation to time of sample collection for baseline VL assessment was 4.4 days (SD 3.6). Of the 532 HIV-positive pregnant women enrolled in the FLC for Option B+ study and newly starting Option B+ without a self-reported history of prior ART use, 29 (5.5%) had uVL and 113 (21.4%) had suppressed VL at baseline. There was no association between participants' age, gravidity, marital status, mean monthly income, educational level, disclosure of HIV status to partner, and uVL or viral suppression at baseline. However, non-disclosure of HIV status to any other person was associated with decreased odds of viral suppression at baseline (OR 0.640; 0.416-0.982). CONCLUSION: Twenty-one percent of HIV-positive Ugandan pregnant women initiating ART (Option B+) showed virological suppression at baseline and were presumed to be "elite controllers" or to have misreported being ART-naive. Further studies are needed to better understand the biologic mechanisms of elite controllers among pregnant women as well as to differentiate elite controllers from concealed ART use. Trial Registration The trial was registered as NCT02515370 (04/08/2015) on Clinicaltrials.gov.

Comparative analysis of perinatal outcomes and birth defects amongst adolescent and older Ugandan mothers: evidence from a hospital-based surveillance database.

BACKGROUND: Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12-19 years) and mothers (age 20-34 years) in four urban hospitals. METHODS: Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson's chi-square. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to mothers 20-34 years. RESULTS: A total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. Adolescent mothers had an increased risk of preterm delivery (aOR: 1.14; CI 1.06-1.23), low birth weight (aOR: 1.46; CI 1.34-1.59), and early neonatal deaths (aOR: 1.58; CI 1.23-2.02). Newborns of adolescent mothers had an increased risk of major external birth defects (aOR: 1.33; CI 1.02-1.76), specifically, gastroschisis (aOR: 3.20; CI 1.12-9.13) compared to mothers 20-34 years. The difference between the prevalence of gastroschisis among adolescent mothers (7.3 per 10,000 births; 95% CI 3.7-14.3) was statistically significant when compared to mothers 20-34 years (1.6 per 10,000 births; 95% CI 0.9-2.6). CONCLUSIONS: This study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20-34 years, similar to findings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population.

Adolescent pregnancies are a global problem occurring in high-, middle-, and low-income countries with Uganda having one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes, including major external birth defects, between adolescents, (age 12­19 years) and mothers (age 20­34 years) in four urban hospitals.All informative births, including live births, stillbirths, and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2018 were examined. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes.Of the 100,189 births, 11.0% were among adolescent mothers and 89.0% among mothers (20­34 years). Adolescent mothers were more likely than mothers (20­34 years) to have an infant with preterm delivery, low birth weight, early neonatal death, and major external birth defects. Adolescent pregnancies were also associated with an increased risk of gastroschisis when compared to mothers (20­34 years).In conclusion, this study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20­34 years. Research on the potential underlying causes or mechanisms for these adverse outcomes among adolescent births is necessary to identify possible interventions.

PMTCT Option B+ 2012 to 2018 - Taking stock: barriers and strategies to improve adherence to Option B+ in urban and rural Uganda.

Since 2012, PMTCT Option B+ has been recommended by the World Health Organization to reduce vertical transmission but numerous adherence challenges remain. We conducted a qualitative study at baseline using six focus group discussions and 14 in-depth interviews to explore knowledge, beliefs, attitudes and challenges towards the Option B+ strategy for PMTCT among HIV-infected pregnant and post-partum women and health workers engaged in Uganda's national Option B+ PMTCT programme. Data were analysed using a thematic approach to capture latent and manifest content with the social ecological model as a theoretic foundation in order to make contextual sense of key stakeholders' needs for an effective Option B+ intervention. Overall, among all study participants, we found multi-level barriers to adhering to Option B+ cutting across all levels of the social ecological model. In line with the model, our study revealed barriers at personal, relational, organizational and societal levels. Some personal beliefs such as that the baby's health is more important that the mother's, organizational (negative attitudes and behaviour of health workers), structural such as poverty, work conflicts, fear and lack of disclosure related to community stigma were all critical obstacles to women adhering to the Option B+ programme. We found that both health workers and participants in the programme have a relatively clear understanding of the benefits of adhering to their treatment; though a more nuanced understanding and thus emphasis in counselling on side effects, is critical to helping patients adhere.

PMTCT Option B+ 2012 to 2018 ­ Taking stock: barriers and strategies to improve adherence to Option B+ in urban and rural Uganda

Since 2012, PMTCT Option B+ has been recommended by the World Health Organization to reduce vertical transmission but numerous adherence challenges remain. We conducted a qualitative study at baseline using six focus group discussions and 14 in-depth interviews to explore knowledge, beliefs, attitudes and challenges towards the Option B+ strategy for PMTCT among HIV-infected pregnant and post-partum women and health workers engaged in Uganda's national Option B+ PMTCT programme. Data were analysed using a thematic approach to capture latent and manifest content with the social ecological model as a theoretic foundation in order to make contextual sense of key stakeholders' needs for an effective Option B+ intervention. Overall, among all study participants, we found multi-level barriers to adhering to Option B+ cutting across all levels of the social ecological model. In line with the model, our study revealed barriers at personal, relational, organizational and societal levels. Some personal beliefs such as that the baby's health is more important that the mother's, organizational (negative attitudes and behaviour of health workers), structural such as poverty, work conflicts, fear and lack of disclosure related to community stigma were all critical obstacles to women adhering to the Option B+ programme. We found that both health workers and participants in the programme have a relatively clear understanding of the benefits of adhering to their treatment; though a more nuanced understanding and thus emphasis in counselling on side effects, is critical to helping patients adhere

A hospital-based birth defects surveillance system in Kampala, Uganda.

BACKGROUND: In 2010, the World Health Assembly passed a resolution calling upon countries to prevent birth defects where possible. Though birth defects surveillance programs are an important source of information to guide implementation and evaluation of preventive interventions, many countries that shoulder the largest burden of birth defects do not have surveillance programs. This paper shares the results of a hospital-based birth defects surveillance program in Uganda which, can be adopted by similar resource-limited countries. METHODS: All informative births, including live births, stillbirths and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2017 were examined for birth defects. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes and entered in an electronic data collection tool. Identified birth defects were confirmed through bedside examination by a physician and review of photographs and a narrative description by a birth defects expert. Informative births (live, still and spontaneous abortions) with a confirmed birth defect were included in the numerator, while the total informative births (live, still and spontaneous abortions) were included in the denominator to estimate the prevalence of birth defects per 10,000 births. RESULTS: The overall prevalence of birth defects was 66.2/10,000 births (95% CI 60.5-72.5). The most prevalent birth defects (per 10,000 births) were: Hypospadias, 23.4/10,000 (95% CI 18.9-28.9); Talipes equinovarus, 14.0/10,000 (95% CI 11.5-17.1) and Neural tube defects, 10.3/10,000 (95% CI 8.2-13.0). The least prevalent were: Microcephaly, 1.6/10,000 (95% CI 0.9-2.8); Microtia and Anotia, 1.6/10,000 (95% CI 0.9-2.8) and Imperforate anus, 2.0/10,000 (95% CI 1.2-3.4). CONCLUSION: A hospital-based surveillance project with active case ascertainment can generate reliable epidemiologic data about birth defects prevalence and can inform prevention policies and service provision needs in low and middle-income countries.

Primary HIV prevention in pregnant and lactating Ugandan women: A randomized trial.

BACKGROUND: The 'Primary HIV Prevention among Pregnant and Lactating Ugandan Women' (PRIMAL) study aimed to assess the effectiveness of an enhanced HIV counseling intervention for preventing HIV acquisition among HIV-uninfected mothers during pregnancy and throughout the breastfeeding period. METHODS: We conducted an unblinded randomized control trial between 22 February 2013 and 22 April 2016 to assess the effectiveness of an extended repeat HIV testing and enhanced counseling (ERHTEC) intervention aimed at preventing primary HIV infection among HIV-uninfected pregnant and lactating women in Uganda. HIV-uninfected pregnant women aged 15-49 were enrolled 1:1 individually or in couples together with their partner. Enrolled women and couples were randomized 1:1 to an intervention (ERHTEC) or control (extended repeat HIV testing and standard counseling) group and followed up to 24 months postpartum or six weeks past complete cessation of breastfeeding, whichever came first. Both groups were tested for sexually transmitted infections (STIs) and HIV at enrollment, delivery, 3 and 6 months postpartum and every 6 months thereafter until the end of follow-up. The intervention group received enhanced HIV prevention counseling every 3 months throughout follow-up. The control group received standard counseling at the time of HIV retesting. Both intervention and control couples were offered couple HIV testing and counseling at all study visits. MAIN OUTCOME MEASURES: Frequency of condom use and incidence of HIV, syphilis, gonorrhea, chlamydia and trichomoniasis over follow-up. RESULTS: Between February 2013 and April 2014, we enrolled 820 HIV-uninfected pregnant women presenting for antenatal care individually (n = 410) or in couples (n = 410 women and 410 partners) in one urban and one rural public Ugandan hospital. Women's median age was 24 years (IQR 20-28 years). At baseline, participants did not differ in any socio-demographic, reproductive health, HIV testing history, sexual behavior, medical history or STI status characteristics; 96% (386/402) of couples were tested and counseled for HIV together with their partners at enrolment, 2.1% (7/329) of whom were found to be HIV-infected. Six hundred twenty-five (76%) women completed follow-up as per protocol (S1 Protocol). Women were followed for an average of 1.76 years and cumulated 1,439 women-years of follow-up or 81% of the maximum 1,779 women-years of follow-up assuming no dropouts. Men were followed for an average of 1.72 years. The frequency of consistent condom use and the proportion of women who used condoms over the last 3 months or at last vaginal sex increased substantially over follow-up in both arms, but there were no statistically significant differences in increases between the intervention and control arms. During follow-up, on average 42% (range 36%-46%) of couple partners were counseled together. Between 3.8% and 7.6% of women tested positive at any follow-up visit for any STI including syphilis, gonorrhea, C. trachomatis or T. vaginalis. Four women (two in each arm) and no enrolled men became infected with HIV, representing an overall HIV incidence rate of 0.186 per 100 person-years. Three of the women seroconverters had enrolled individually, one as a couple. At or before seroconversion, all four women reported their partners had extramarital relationships and/or had not disclosed their suspected HIV-infected status. There were no statistically significant differences between study arms for STI or HIV incidences. CONCLUSIONS: A sustained enhanced HIV prevention counseling intervention for up to 2 years postpartum among pregnant and breastfeeding women did not have a statistically significant effect on condom use or HIV incidence among these women. However, in both study arms, condom use increased over follow-up while STI and HIV incidence remained very low when compared to similar cohorts in and outside Uganda, suggesting that repeat HIV testing during breastfeeding, whether with enhanced or standard counseling, may have had an unintended HIV preventive effect among pregnant and lactating women in this setting. Further research is needed to verify this hypothesis. TRIAL REGISTRATION: ClinicalTrials.gov NCT01882998.

Comparative effects of three methods of promoting breastfeeding among human immunodeficiency virus-infected women in Uganda: a parallel randomized clinical trial.

Background: The objective of this study was to evaluate the comparative effects of three breastfeeding promotion interventions on the duration of exclusive breastfeeding (EBF) and any breastfeeding (BF) among human immunodeficiency virus (HIV)-infected women in Uganda. Methods: Between February 2012 and February 2013, 218 HIV-infected pregnant mothers were randomly assigned to (A) standard care (n=73), (B) enhanced family/peer support (n=72) or (C) enhanced nutrition education (n=73). Results: The prevalence (%) of EBF/BF did not differ between intervention arms at the sixth (A, 85/92; B, 84/91; C, 87/89) and ninth (A, 17/91; B, 18/89; C, 16/87) postpartum month assessments (p>0.05). However, the risk of early BF cessation differed between intervention arms depending on the mother's level of formal education (p=0.04). Among women with no formal education, the risk of early BF cessation was 88% (adjusted hazard ratio [aHR] 0.12 [95% confidence interval {CI} 0.05-0.30]) and 93% (aHR 0.07 [95% CI 0.03-0.18]) lower in arms B and C, respectively, than in arm A (p<0.01). HIV status disclosure to a partner was associated with a higher risk of early EBF (p=0.03) and BF (p=0.04) cessation. Conclusions: In resource-limited settings, enhanced (vs standard care) EBF promotion interventions may not differentially influence EBF but reduce the risk of early BF cessation among women with no formal education. Targeted enhanced interventions among women with no formal education and a mother's partner may be critical to reducing the risk of early EBF/BF cessation.

Use of peers, community lay persons and Village Health Team (VHT) members improves six-week postnatal clinic (PNC) follow-up and Early Infant HIV Diagnosis (EID) in urban and rural health units in Uganda: A one-year implementation study.

BACKGROUND: Effective Prevention of Mother to child Transmission of HIV (PMTCT) relies heavily on follow-up of HIV-infected women and infants from antenatal, through postnatal, to the end of the breastfeeding period. In Uganda, postnatal (PNC) follow-up remains below 50 % creating a missed opportunity for linkage to comprehensive HIV care and early infant diagnosis (EID). We evaluated the use of HIV infected peer mothers (peers), community lay persons and Village health team (VHT) members to improve PNC follow up and EID in urban and rural health units. METHODS: Study participants were HIV-infected women recruited from antenatal clinics at three urban clinics (Mulago, Rubaga and Mengo hospitals) and one rural health centre (Mpigi Health centre IV) between January and September 2010. The women were followed through delivery and the mother-infant pairs for the 6-week postnatal visit and up to 14 weeks for EID. Peers, community lay persons and VHT members were identified and trained in basic PMTCT and reproductive health (RH). They were then assigned to study clinic to support and follow study participants, their partners and infants through provision of health education, counseling, home visits, and phone call reminders. Six week PNC attendance was measured as a proportion of mother-infant pairs that returned for the 6-week postnatal follow up visit (5-8 weeks) while EID was measured as the proportion of HIV-exposed live birth that had an HIV test done by 14 weeks of age. Data at baseline (one year before the intervention) was compared with that during the one year study period among study participants and HIV infected women and their HIV-exposed infants in the whole clinic population. RESULTS: A total of 558 HIV-infected pregnant women were recruited for the study, 47 mother-infant pairs were censured before 6 weeks due to stillbirth (14), infant death < 6 weeks (23), death of participant (04) and loss to follow up before delivery (6). 401/511 (78.5 %) of mother-infant pairs returned to the study clinics at six-week, while 441/511 (86.3 %) infants were tested for HIV infection by 14 weeks of age. The baseline six-week PNC follow up was 37.7 % and increased during the study period to 78.5 % and 39.1 % among study participants and whole clinic population respectively, an incremental difference of 39.4 % (P < 0.001). EID increased from a baseline of 53.6 % to 86.3 % and 65.8 % among study and whole clinic population respectively during the study period, an incremental difference of 20.5 % (P < 0.001). CONCLUSIONS: Use of peers, community lay persons and VHT members led to a significant increase in six-week postnatal follow up of HIV infected women and EID among HIV exposed infants in the four study clinics. Our study supports the use of peers to improve early postnatal follow up and EID and should be implemented in other health units to support the PMTCT cascade.

The impact of maternal highly active antiretroviral therapy and short-course combination antiretrovirals for prevention of mother-to-child transmission on early infant infection rates at the Mulago national referral hospital in Kampala, Uganda, January 2007 to May 2009.

BACKGROUND: Early HIV infant diagnosis and treatment have been shown to dramatically improve survival in infants. Despite these findings, infants accessing HIV diagnosis and treatment remain low in Uganda. We describe the antiretroviral (ARV) drugs given in the Mulago Hospital prevention of mother-to-child transmission (PMTCT) program from January 2007 to May 2009 and its impact on early infant HIV infection rates. METHODS: Pregnant women identified as HIV infected in the Mulago antenatal clinics received one of the following regimens: short-course ARV prophylaxis plus single-dose nevirapine (sdNVP) in labor, highly active antiretroviral therapy (HAART), or sdNVP if they presented in labor. Infants received sdNVP and zidovudine (ZDV) for 1 week. Infants HIV diagnosis was done from 6 weeks after delivery. RESULTS: 62.3% of HIV-infected women received combination ARVs, including HAART. Early infection rates were highest among infants with no maternal ARV [36.4; 95% confidence interval (CI): 17.2 to 59.3] or only sdNVP (11.2; 95% CI: 8.1 to 14.8). Similar rates were observed for the group that took short-course ARVs, ZDV/sdNVP (4.6; 95% CI: 3.2 to 6.4), and ZDV/lamivudine/sdNVP (4.9; 95% CI: 3.1 to 7.2) and lowest rates for those that took HAART (1.7: 95% CI: 0.8 to 2.8). Overall infection rate was 5.0% (95% CI: 4.1 to 5.9). CONCLUSIONS: Findings indicate low rates of infant infection for mothers receiving combination ARVs. These findings demonstrate that provision of combination ARV for PMTCT is feasible and effective in busy referral hospital's PMTCT programs in resource-limited settings.