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.

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).

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 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.

Indirect effects of COVID-19 on maternal, neonatal, child, sexual and reproductive health services in Kampala, Uganda.

BACKGROUND: COVID-19 impacted global maternal, neonatal and child health outcomes. We hypothesised that the early, strict lockdown that restricted individuals' movements in Uganda limited access to services. METHODS: An observational study, using routinely collected data from Electronic Medical Records, was carried out, in Kawempe district, Kampala. An interrupted time series analysis assessed the impact on maternal, neonatal, child, sexual and reproductive health services from July 2019 to December 2020. Descriptive statistics summarised the main outcomes before (July 2019-March 2020), during (April 2020-June 2020) and after the national lockdown (July 2020-December 2020). RESULTS: Between 1 July 2019 and 31 December 2020, there were 14 401 antenatal clinic, 33 499 deliveries, 111 658 childhood service and 57 174 sexual health attendances. All antenatal and vaccination services ceased in lockdown for 4 weeks.During the 3-month lockdown, the number of antenatal attendances significantly decreased and remain below pre-COVID levels (370 fewer/month). Attendances for prevention of mother-to-child transmission of HIV dropped then stabilised. Increases during lockdown and immediately postlockdown included the number of women treated for high blood pressure, eclampsia and pre-eclampsia (218 more/month), adverse pregnancy outcomes (stillbirths, low-birth-weight and premature infant births), the rate of neonatal unit admissions, neonatal deaths and abortions. Maternal mortality remained stable. Immunisation clinic attendance declined while neonatal death rate rose (from 39 to 49/1000 livebirths). The number of children treated for pneumonia, diarrhoea and malaria decreased during lockdown. CONCLUSION: The Ugandan response to COVID-19 negatively impacted maternal, child and neonatal health, with an increase seen in pregnancy complications and fetal and infant outcomes, likely due to delayed care-seeking behaviour. Decreased vaccination clinic attendance leaves a cohort of infants unprotected, affecting all vaccine-preventable diseases. Future pandemic responses must consider impacts of movement restrictions and access to preventative services to protect maternal and child health.

Pregnant women, their male partners and health care providers' perceptions of HIV self-testing in Kampala, Uganda: Implications for integration in prevention of mother-to-child transmission programs and scale-up.

BACKGROUND: HIV status awareness is critical for HIV prevention and care but HIV testing rates remain low in Uganda, especially among men. One suggested approach to increase access and utilisation of HIV testing services is HIV self-testing. We explored perceptions of pregnant and lactating women and their male partners who attended antenatal care, and health care providers in a government hospital in Kampala, Uganda, about HIV self-testing for initial or repeat testing for women and their partners during pregnancy and postpartum We draw implications for scaling-up this new testing approach in Uganda. METHODS: This was a qualitative study conducted at Mulago National Referral Hospital, Kampala, Uganda, between April and December 2017. We conducted in-depth interviews with five pregnant or lactating women and their five male partners; five focus group discussions (two with women, two with health workers and one with male partners of women attending antenatal care) and five key informant interviews with health workers providing prevention of mother-to-child HIV transmission (PMTCT) services. Data were analysed using content thematic approach. RESULTS: There was limited awareness about HIV self-testing especially among pregnant or lactating women and their male partners. Study participants mentioned that HIV self-testing would enable people to know their HIV status faster, they thought the approach would be cost- and time-saving compared to health facility-based HIV testing, improve confidentiality and reduce stigma for those who test HIV positive. They expressed however, a general fear that HIV self-testing would lead to harm to self and others in case one tested HIV positive, including suicide, violence among couples, intentional transmission of HIV, and limited linkage to care due to lack of counselling. The likely misinterpretation of HIV test results especially among those with no or limited education, and possible coercion exerted by male partners on their wives were other potential concerns raised about the use of HIV self-testing. CONCLUSIONS: There was limited knowledge about HIV self-testing among pregnant and lactating women, their partners and health workers. While the self-testing modality was perceived to be critical for helping people, especially those in casual and distant relationships, to know their HIV status and that of their partners, most study participants believed that HIV self-testing could potentially result in a multitude of negative outcomes in the absence of pre- and post-test counselling. Successful scale-up and integration of self-testing in HIV programs requires community education, provision of information materials and making self-test kits accessible and affordable, especially in rural areas.

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.

"[Repeat] testing and counseling is one of the key [services] that the government should continue providing": participants' perceptions on extended repeat HIV testing and enhanced counseling (ERHTEC) for primary HIV prevention in pregnant and lactating women in the PRIMAL study, Uganda.

BACKGROUND: The 'Primary HIV Prevention among Pregnant and Lactating Ugandan Women' (PRIMAL) randomized controlled trial aimed to assess an enhanced counseling strategy linked to extended postpartum repeat HIV testing and enhanced counseling among 820 HIV-negative pregnant and lactating women aged 18-49 years and 410 of their male partners to address the first pillar of the WHO Global Strategy for the Prevention of Mother-to-Child HIV transmission (PMTCT). This paper presents findings of qualitative studies aimed at evaluating participants' and service providers' perceptions on the acceptability and feasibility of the intervention and at understanding the effects of the intervention on risk reduction, couple communication, and emotional support from women's partners. METHODS: PRIMAL Study participants were enrolled from two antenatal care clinics and randomized 1:1 to an intervention or control arm. Both arms received repeat sexually transmitted infections (STI) and HIV testing at enrolment, labor and delivery, and at 3, 6, 12, 18 and 24 months postpartum. The intervention consisted of enhanced quarterly counseling on HIV risk reduction, couple communication, family planning and nutrition delivered by study counselors through up to 24 months post-partum. Control participants received repeat standard post-test counseling. Qualitative data were collected from intervention women participants, counsellors and midwives at baseline, midline and end of the study through 18 focus group discussions and 44 key informant interviews. Data analysis followed a thematic approach using framework analysis and a matrix-based system for organizing, reducing, and synthesizing data. RESULTS: At baseline, FGD participants mentioned multiple sexual partners and lack of condom use as the main risks for pregnant and lactating women to acquire HIV. The main reasons for having multiple sexual partners were 1) the cultural practice not to have sex in the late pre-natal and early post-natal period; 2) increased sexual desire during pregnancy; 3) alcohol abuse; 4) poverty; and 5) conflict in couples. Consistent condom use at baseline was limited due to lack of knowledge and low acceptance of condom use in couples. The majority of intervention participants enrolled as couples felt enhanced counselling improved understanding, faithfulness, mutual support and appreciation within their couple. Another benefit mentioned by participants was improvement of couple communication and negotiation, as well as daily decision-making around sexual needs, family planning and condom use. Participants stressed the importance of providing counselling services to all couples. CONCLUSION: This study shows that enhanced individual and couple counselling linked to extended repeat HIV and STI testing and focusing on HIV prevention, couple communication, family planning and nutrition is a feasible and acceptable intervention that could enhance risk reduction programs among pregnant and lactating women. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT01882998, date of registration 21st June 2013.

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

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.