The role of community engagement in promoting research participants' understanding of pharmacogenomic research results: Perspectives of stakeholders involved in HIV/AIDS research and treatment.

Community engagement (CE) is praised to be a powerful vehicle in empowering communities with knowledge and skills to make informed decisions for better health care. Several CE approaches have been proposed to improve participants' and research communities' understanding of genomic research including pharmacogenomic information and results. However, there is limited literature on how these approaches can be used to communicate findings of pharmacogenomic research to communities of people living with HIV. This study explored stakeholders' perspectives on the role of community engagement in promoting understanding of pharmacogenomic research results among people living with HIV. We adopted a qualitative approach that involved 54 stakeholders between September 2021 and February 2022. We held five focus group discussions among 30 community representatives from five research institutions, 12 key informant interviews among researchers, and 12 in-depth interviews among ethics committee members. A thematic approach was used to analyze the results. Five themes merged from this data and these included (i) benefits of engaging communities prior to returning individual pharmacogenomic research results to participants. (ii) Obtaining community consensus on the kinds of pharmacogenomic results to be returned. (iii) Opinions on how pharmacogenomic research information and results should be communicated at community and individual levels. (iv) Perceived roles of community stakeholders in promoting participants' understanding and utilization of pharmacogenomic research results. (v) Perceived challenges of engaging communities when returning individual results to research participants. Stakeholders opined that CE facilitates co-learning between researchers and research communities. Researchers can adapt existing CE approaches that are culturally acceptable for meaningful engagement with minimal ethical and social risks when communicating pharmacogenomic research results. CE approaches can facilitate understanding of pharmacogenomic research and findings among research participants and communities. Therefore, if creatively adapted, existing and new CE approaches can enable researchers to communicate simple and understandable results of pharmacogenomic research.

Support, not blame: safe partner disclosure among women diagnosed with HIV late in pregnancy in South Africa and Uganda.

BACKGROUND: HIV partner disclosure rates remain low among pregnant women living with HIV in many African countries despite potential benefits for women and their families. Partner disclosure can trigger negative responses like blame, violence, and separation. Women diagnosed with HIV late in pregnancy have limited time to prepare for partner disclosure. We sought to understand challenges around partner disclosure and non-disclosure faced by women diagnosed with HIV late in pregnancy in South Africa and Uganda and to explore pathways to safe partner disclosure. METHODS: We conducted in-depth interviews and focus group discussions with pregnant women and lactating mothers living with HIV (n = 109), disaggregated by antenatal care (ANC) initiation before and after 20 weeks of gestation, male partners (n = 87), and health workers (n = 53). All participants were recruited from DolPHIN2 trial sites in Kampala (Uganda) and Gugulethu (South Africa). Topic guides explored barriers to partner disclosure, effects of non-disclosure, strategies for safe disclosure. Using the framework analysis approach, we coded and summarised data based on a socio-ecological model, topic guides, and emerging issues from the data. Data was analysed in NVivo software. RESULTS: Our findings illustrate pregnant women who initiate ANC late experience many difficulties which are compounded by the late HIV diagnosis. Various individual, interpersonal, community, and health system factors complicate partner disclosure among these women. They postpone or decide against partner disclosure mainly for own and baby's safety. Women experience stress and poor mental health because of non-disclosure while demonstrating agency and resilience. We found many similarities and some differences around preferred approaches to safe partner disclosure among female and male participants across countries. Women and male partners preferred healthcare workers to assist with disclosure by identifying the 'right' time to disclose, mentoring women to enhance their confidence and communication skills, and providing professional mediation for partner disclosure and couple testing. Increasing the number of counsellors and training them on safe partner disclosure was deemed necessary for strengthening local health services to improve safe partner disclosure. CONCLUSION: HIV diagnosis late in pregnancy amplifies existing difficulties among pregnant women. Late ANC initiation is an indicator for the likelihood that a pregnant woman is highly vulnerable and needs safeguarding. Respective health programmes should be prepared to offer women initiating ANC late in pregnancy additional support and referral to complementary programmes to achieve safe partner disclosure and good health.

It Takes A Village; Involvement of Village Health Teams to Develop Tools and Resources to Communicate about Antiretroviral Use in Pregnancy and Breastfeeding at Community Level in Uganda.

Background: Research findings must be communicated to the populations who will benefit from them, in a manner that is accessible and understandable. Aims: We recently generated novel data on medication use in breastfeeding. A Faculty of Health and Life Sciences (Liverpool) grant enabled work with a team of Village Health Teams (VHTs) in Hoima, rural Uganda, to co-create related communication materials for use in their house-to-house visitation and health education. Methods: After an initial workshop from 24th to 26th March 2021, training and review of draft materials, 10 VHT pairs visited 50 households in Hoima district. Basic demographic data were collected alongside preferred communication methods. VHTs provided feedback and re-design of materials commenced. This included dramatization of scenarios and photography. A second round of house-to-house visitation informed final adjustments. We conducted focused group discussions and a dissemination workshop attended by VHTs, local healthcare leaders and journalists was hosted on 16th - 17th June 2022. Results: Most households (74%) had a breastfeeding baby. Majority could read and had access to radios (60%), but not to smartphones (58%) or television (86%). Most preferred verbal and visual aids for health education, and requested images of "people who look like us".Final co-created materials included posters in English and Runyoro and laminated 'job aids' in both languages . These continue to be in active use. VHTs and community members requested future projects of this nature. Conclusion: Healthcare communication to communities must be accessible and clear. Representation of images that the public can identify with is important. Co-creation workshops were successful in rural Uganda, and pave the way for future collaborative, participatory research.

Perceptions and Attitudes Toward an Interactive Voice Response Tool (Call for Life Uganda) Providing Adherence Support and Health Information to HIV-Positive Ugandans: Qualitative Study.

BACKGROUND: The continuing decline in AIDS-related deaths in the African region is largely driven by the steady scale-up of antiretroviral therapy. However, there are challenges to retaining people living with HIV on treatment. Call for Life Uganda (CFLU) is an interactive voice response tool using simple analogue phones. CFLU supports patients with daily pill reminders, preappointment reminders, symptom reporting and management, and weekly health promotion tips. Mobile health tools are being increasingly used in resource-limited settings but are often adopted without rigorous evaluation. OBJECTIVE: This qualitative study conducted at 12 months after enrollment assessed patients' experiences, perceptions, and attitudes regarding CLFU. METHODS: We conducted a qualitative substudy within an open-label randomized controlled trial titled "Improving outcomes in HIV patients using mobile phone based interactive software support." Data were collected through 6 focus group discussions with participants sampled based on proportion of calls responded to-<25%, between 25% and 50%, and >50%-conducted at the Infectious Diseases Institute, Mulago, and the Kasangati Health Centre IV. NVivo (version 11; QSR International) was used in the management of the data and in the coding of the emerging themes. The data were then analyzed using content thematic analysis. RESULTS: There was consensus across all groups that they had more positive than negative experiences with the CFLU system. Participants who responded to >50% of the calls reported more frequent use of the specific elements of the CFLU tool and, consequently, experienced more benefits from the system than those who responded to calls less frequently. Irrespective of calls responded to, participants identified pill reminders as the most important aspect in improved quality of life, followed by health promotion tips. The most common challenge faced was difficulty with the secret personal identification number. CONCLUSIONS: Findings showed participants' appreciation, high willingness, and interest in the intervention, CFLU, that demonstrated great perceived potential to improve their access to health care; adherence to treatment; health awareness; and, consequently, quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT02953080; https://clinicaltrials.gov/ct2/show/NCT02953080.

Researchers experience of using the regulatory affairs information system (RAIS) in strengthening research compliance in a large research program: A case study of the Infectious Diseases Institute (IDI) in Uganda.

Objective: The aim of this study was to explore researchers' experience of using the regulatory affairs information system (RAIS) in strengthening research compliance to national ethics guidelines through tracking ethics and regulatory approvals for research projects at the Infectious Diseases Institute. Methods: We conducted a cross-sectional study using purposive sampling of 50 participants who were principal investigators (PI) and study coordinators (SC) of active projects between November 2019 and January 2020. Only 36 of them responded to the survey. We also conducted 12 key informant interviews among PI, SC, and research management at the Institute. We used STATA 13 to analyze responses to the survey. The interviews lasted between 20 and 30 min. We used NVivo 10 software to manage the transcripts and generation of themes. Results: Majority 19 (52.8%) of those who participated in the survey were study coordinators, 19 (52.8%) had participated in more than 5 research studies, 28 (90.3%) had ever received a notification from the RAIS and 26 (92.9%) submitted requests for renewal of their studies approvals to Ethics committees and regulatory bodies 4 weeks prior to expiration dates. The study also examined participants' general understanding of the regulatory requirements and all were aware that RECs and NDA grant approval for a period of 1 year, and 35 (97.2%) that UNCST grants approval for the duration of the study. Three prominent themes; researchers' experiences, benefits, and shortcomings of RAIS were generated from the key informant interviews. Discussion: Having experience in research coupled with a novel automated system provides a platform for a better understanding of research regulatory requirements, hence compliance to the national guidelines. Conclusion: Our case study demonstrates that supporting researchers and research institutions in low resource settings with an automated system in tracking expiration dates for research approvals can facilitate compliance to national ethics guidelines.

72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study.

BACKGROUND: Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. METHODS: DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz group had a viral load of less than 50 copies per mL. Of 57 (21%) mothers with a severe adverse event, three (2%) in the dolutegravir group and five (4%) in the efavirenz group were related to the drug (dolutegravir drug-related events were one woman each with suicidal ideation, suicide attempt, herpes zoster meningitis; efavirenz drug-related events were one woman each with suicide attempt and liver cirrhosis, and three people with drug-induced liver injury). Of 136 (56%) infants in whom severe adverse events were recorded, none were related to the study drugs. In addition to the three infant HIV infections detected at birth in the dolutegravir group that have been previously reported, an additional transmission in the efavirenz group occurred during breastfeeding despite optimal maternal viral suppression and serial negative infant tests in the first year of life. INTERPRETATION: Dolutegravir was safe and well tolerated, supporting updated WHO treatment recommendations in pregnant and breastfeeding women. Infant HIV transmissions can occur during breastfeeding despite persistently undetectable maternal viral load highlighting the need for continued infant testing. FUNDING: Unitaid.

'I fear my partner will abandon me': the intersection of late initiation of antenatal care in pregnancy and poor ART adherence among women living with HIV in South Africa and Uganda.

BACKGROUND: Many women in sub-Saharan Africa initiate antenatal care (ANC) late in pregnancy, undermining optimal prevention of mother-to-child-transmission (PMTCT) of HIV. Questions remain about whether and how late initiation of ANC in pregnancy is related to adherence to antiretroviral therapy (ART) in the era of national dolutegravir roll-out. METHODS: This study employed a qualitative design involving individual interviews and focus group discussions conducted between August 2018 and March 2019. We interviewed 37 pregnant and lactating women living with HIV selected purposively for early or late presentation to ANC from poor urban communities in South Africa and Uganda. Additionally, we carried out seven focused group discussions involving 67 participants in both countries. Data were analysed thematically in NVivo12. RESULTS: Women described common underlying factors influencing both late ANC initiation and poor ART adherence in South Africa and Uganda. These included poverty and time constraints; inadequate health knowledge; perceived low health risk; stigma of HIV in pregnancy; lack of disclosure; and negative provider attitudes. Most late ANC presenters reported relationship problems, lack of autonomy and the limited ability to dialogue with their partners to influence household decisions on health and resource allocation. Perception of poor privacy and confidentiality in maternity clinics was rife among women in both study settings and compounded risks associated with early disclosure of pregnancy and HIV. Women who initiated ANC late and were then diagnosed with HIV appeared to be more susceptible to poor ART adherence. They were often reprimanded by health workers for presenting late which hampered their participation in treatment counselling and festered provider mistrust and subsequent disengagement in care. Positive HIV diagnosis in late pregnancy complicated women's ability to disclose their status to significant others which deprived them of essential social support for treatment adherence. Further, it appeared to adversely affect women's mental health and treatment knowledge and self-efficacy. CONCLUSIONS: We found clear links between late initiation of ANC and the potential for poor adherence to ART based on common structural barriers shaping both health seeking behaviours, and the adverse impact of late HIV diagnosis on women's mental health and treatment knowledge and efficacy. Women who present late are a potential target group for better access to antiretrovirals that are easy to take and decrease viral load rapidly, and counselling support with adherence and partner disclosure. A combination of strengthened health literacy, economic empowerment, improved privacy and patient-provider relationships as well as community interventions that tackle inimical cultural practices on pregnancy and unfair gender norms may be required.

"It's only fatness, it doesn't kill": a qualitative study on perceptions of weight gain from use of dolutegravir-based regimens in women living with HIV in Uganda.

BACKGROUND: Dolutegravir (DTG)-based regimens have been recommended by the WHO as the preferred first-line and second-line HIV treatment in all populations. Evidence suggests an association with weight gain, particularly among black women. Our study investigated perceptions of weight gain from DTG-based regimen use on body image and adherence of antiretroviral therapy in women living with HIV (WLHIV) in Uganda. METHODS: Between April and June 2021, we conducted semi-structured interviews involving 25 WLHIV (adolescents, women of reproductive potential and post-menopausal women) and 19 healthcare professionals (clinicians, nurses, ART managers and counsellors) purposively selected from HIV clinics in Kampala. The interviews explored perceptions of body weight and image; experiences and management of weight related side effects associated with DTG; and knowledge and communication of DTG-related risks. Data was analysed thematically in NVivo 12 software. RESULTS: Our findings indicate WLHIV in Uganda commonly disliked thin body size and aspired to gain moderate to high level body weight to improve their body image, social standing and hide their sero-positive status. Both WLHIV and healthcare professionals widely associated weight gain with DTG use, although it was rarely perceived as an adverse event and was unlikely to be reported or to alter medication adherence. Clinical management and pharmacovigilance of DTG-related weight gain were hampered by the limited knowledge of WLHIV of the health risks of being over-weight and obesity; lack of diagnostic equipment and resources; and limited clinical guidance for managing weight gain and associated cardiovascular and metabolic comorbidities. CONCLUSIONS: The study highlights the significance of large body-size in promoting psychosocial wellbeing in WLHIV in Uganda. Although weight gain is recognized as a side effect of DTG, it may be welcomed by some WLHIV. Healthcare professionals should actively talk about and monitor for weight gain and occurrence of associated comorbidities to facilitate timely interventions. Improved supply of diagnostic equipment and support with sufficient guidance for managing weight gain for healthcare professionals in Uganda are recommended.

Intrapreneurship and technological innovation in optimizing qualitative research as evidenced at Infectious Diseases Institute, Uganda.

BACKGROUND: Discrepancies between what is transcribed and the actual interview recordings were noticed in qualitative research reports. This study aimed at the development of a new transcription software (Jiegnote), and the evaluation of its effectiveness in the optimization of the transcription process, to minimize transcription completion time, and errors in qualitative research. METHODS: The study was a mixed methods project implemented from September to November 2020. The qualitative aspect of the study was phenomenological in perspective whereas the quantitative consisted of a randomized controlled trial (RCT) with a parallel design. RESULTS: At the time of the study, the Jiegnote software was a working prototype. We enrolled a total of 26 participants; 14 participants had their data analyzed in the RCT part of the study, 13 participated in the in-depth interviews, and 22 in the answering of Semi Structured Questionnaires. Upon the execution of an independent t test, results showed that, there was no statistical significance between the intervention and control means. On considering the total average transcription completion time and the type of language in which an audio case was recorded, the effect size evaluation implied that the Jiegnote software had a small impact (Hedges' g = 0.413438) in reducing the total average time taken to translate and transcribe audio cases that were recorded in a local language (Luganda), and a large impact (Hedges' g = 1.190919) in reducing the total average time taken to transcribe audio cases that were recorded in a foreign language (English). On considering the total average number of transcription errors and the type of language in which an audio case is recorded, the effect size evaluation implied that the Jiegnote software had a small impact (Hedges' g = 0.213258) in reducing the total average time taken to translate and transcribe audio cases that were recorded in a local language (Luganda). This was further observed (Hedges' g = 0.039928) in the transcription of cases that were recorded in a foreign language (English). On considering the in-depth interview data outcomes, participants responded that the Jiegnote software media looping functions (algorithm) enabled them to accomplish their transcription tasks in a shorter time and with fewer errors compared to the traditional methods. CONCLUSION: The study demonstrates utilities associated with intrapreneurship and technological innovation in an organization setting whereby, the Jiegnote technology that was developed by the researchers, had some impact on the optimization of the qualitative research value chain. This was observed through the effect size (impact) evaluations that were conducted to investigate the superiority of the Jiegnote software against the traditional transcription methods, in minimizing the average number of errors committed, and time taken to complete a transcription process.

Patient experiences of switching from Efavirenz- to Dolutegravir-based antiretroviral therapy: a qualitative study in Uganda.

BACKGROUND: In 2019, the World Health Organisation (WHO) recommended Dolutegravir (DTG) as the preferred first-line antiretroviral treatment (ART) for all persons with HIV. ART regimen switches may affect HIV treatment adherence. We sought to describe patient experiences switching from EFV to DTG-based ART in Kampala, Uganda. METHODS: Between July and September 2019, we purposively sampled adults living with HIV who had switched to DTG at the Infectious Diseases Institute HIV clinic. We conducted in-depth interviews with adults who switched to DTG, to explore their preparation to switch and experiences on DTG. Interviews were audio-recorded, transcribed and analysed thematically using Atlas ti version 8 software. RESULTS: We interviewed 25 adults: 18 (72%) were women, and the median age was 35 years (interquartile range [IQR] 30-40). Median length on ART before switching to DTG was 67 months (IQR 51-125). Duration on DTG after switching was 16 months (IQR 10-18). Participants reported accepting provider recommendations to switch to DTG mainly because they anticipated that swallowing a smaller pill once a day would be more convenient. While most participants initially felt uncertain about drug switching, their providers offer of frequent appointments and a toll-free number to call in the event of side effects allayed their anxiety. At the same time, participants said they felt rushed to switch to the new ART regimen considering that they had been on their previous regimen(s) for several years and the switch to DTG happened during a routine visit when they had expected their regular prescription. Some participants felt unprepared for new adverse events associated with DTG and for the abrupt change in treatment schedule. Most participants said they needed additional support from their health providers before and after switching to DTG. CONCLUSION AND RECOMMENDATIONS: Adults living with HIV stable on an EFV-based regimen but were switched to DTG in a program-wide policy change found the duration between counselling and drug switching inadequate. DTG was nonetheless largely preferred because of the small pill size, once daily dosing, and absence of EFV-like side effects. Community-engaged research is needed to devise acceptable ways to prepare participants for switching ART at scale.

Acceptability of a Mobile Phone Support Tool (Call for Life Uganda) for Promoting Adherence to Antiretroviral Therapy Among Young Adults in a Randomized Controlled Trial: Exploratory Qualitative Study.

BACKGROUND: Adherence to treatment is critical for successful treatment outcomes. Although factors influencing antiretroviral therapy (ART) adherence vary, young adults are less likely to adhere owing to psychosocial issues such as stigma, ART-related side effects, and a lack of access to treatment. The Call for Life Uganda (CFLU) mobile health (mHealth) tool is a mobile phone-based technology that provides text messages or interactive voice response functionalities through a web interface and offers 4 modules of support. OBJECTIVE: This study aims to describe the acceptability and feasibility of a mobile phone support tool to promote adherence to ART among young adults in a randomized controlled trial. METHODS: An exploratory qualitative design with a phenomenological approach at 2 study sites was used. A total of 17 purposively selected young adults with HIV infection who had used the mHealth tool CFLU from 2 clinics were included. In total, 11 in-depth interviews and 1 focus group discussion were conducted to examine the following topics: experience with the CFLU tool (benefits and challenges), components of the tool, the efficiency of the system (level of comfort, ease, or difficulty in using the system), how CFLU resolved adherence challenges, and suggestions to improve CFLU. Participants belonged to 4 categories of interest: young adults on ART for the prevention of mother-to-child transmission, young adults switching to or on the second-line ART, positive partners in an HIV-discordant relationship, and young adults initiating the first-line ART. All young adults had 12 months of daily experience using the tool. Data were analyzed using NVivo version 11 software (QSR International Limited) based on a thematic approach. RESULTS: The CFLU mHealth tool was perceived as an acceptable intervention; young adults reported improvement in medication adherence, strengthened clinician-patient relationships, and increased health knowledge from health tips. Appointment reminders and symptom reporting were singled out as beneficial and helped to address the problems of forgetfulness and stigma-related issues. HIV-related stigma was reported by a few young people. Participants requested extra support for scaling up CFLU to make it more youth friendly. Improving the tool to reduce technical issues, including network outages and a period of software failure, was suggested. They suggested that in addition to digital solutions, other support, including the promotion of peer support meetings and the establishment of a designated space and staff members for youth, was also important. CONCLUSIONS: This mHealth tool was an acceptable and feasible strategy for improving ART adherence and retention among young adults in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02953080; https://clinicaltrials.gov/ct2/show/NCT02953080.

Community acceptability of dolutegravir-based HIV treatment in women: a qualitative study in South Africa and Uganda.

BACKGROUND: Despite concerns about dolutegravir use in pregnancy, most low- and middle-income countries are accelerating the introduction of dolutegravir-based regimens into national antiretroviral treatment programmes. Questions remain about the acceptability of dolutegravir use in women due to the potential risks in pregnancy. This study from South Africa and Uganda explored community values, preferences and attitudes towards the use of dolutegravir-based regimens in women. METHODS: This study employed a qualitative design involving in-depth interviews and focus group discussion conducted between August 2018 to March 2019. The study was conducted in the months following an announcement of a potential risk for neural tube defects with dolutegravir use among women during conception and the first trimester. Participants included HIV positive pregnant and lactating women and their partners. They were selected purposively from urban poor communities in South Africa and Uganda. Data was analysed thematically in NVivo. RESULTS: Forty-four in-depth interviews and 15 focus group discussions were conducted. Most participants had positive views of dolutegravir-based regimens and perceived it to be more desirable compared with efavirenz-containing regimens. There was widespread concern about use of dolutegravir during pregnancy and among women of childbearing age due to publicity around the possible association with neural tube defects. Acceptability was gendered, with nearly all male participants preferring their female spouses of childbearing potential not to use dolutegravir, while most women not planning pregnancy wanted access to contraception alongside dolutegravir. Community awareness and knowledge of dolutegravir was low and characterised by negative information. Women were concerned about HIV-related stigma and wanted the privacy features of dolutegravir to be strengthened with modification of the pill appearance and disguised packaging. CONCLUSIONS: Dolutegravir-based regimens were found to be generally acceptable for use in women except during pregnancy. Interest in a dolutegravir-based regimen was linked with its perceived potential to enhance health, privacy and reduce stigma while concerns about neural tube defects were the main potential barrier to dolutegravir uptake in women. In order to optimise the community acceptability and uptake of acceptability-based regimen among women it is critical to strengthen community awareness and understanding of dolutegravir treatment, improve contraception services alongside the introduction of dolutegravir, and engage with male partners.

Engendering health systems in response to national rollout of dolutegravir-based regimens among women of childbearing potential: a qualitative study with stakeholders in South Africa and Uganda.

BACKGROUND: In the era of rapid dolutegravir rollout, concerns about neural tube defects have complicated the health systems response among women of childbearing potential. This qualitative study, which was nested within the DolPHIN-2 clinical trial, examined the current and future health system opportunities and challenges associated with the transition to dolutegravir-based regimen as first line antiretroviral therapy among women of childbearing potential in South Africa and Uganda. METHOD: Semi-structured in-depth interviews with members of antiretroviral therapy guideline development groups and affiliates were conducted. Thirty-one participants were purposively selected for the study, including senior officials from the Ministry of Health and National Drug Regulatory Authority in Uganda and South Africa as well as health-sector development partners, activists, researchers and health workers. A thematic approach was used to analyse the data. FINDINGS: Despite differences in health system contexts, several common challenges and opportunities were identified with the transition among women of childbearing potential in South Africa and Uganda. In both contexts national stakeholders identified challenges with ensuring gender equity in roll out due to the potential teratogenicity of dolutegravir, paucity of data on dolutegravir use in pregnancy, potential stock out of effective contraceptives, poorly integrated contraception services, and limited pharmacovigilance in pregnancy. Participants identified opportunities that could be harnessed to accelerate the transition, including high stakeholder interest and commitment to transition, national approval and licensure of a generic tenofovir/lamivudine/dolutegravir regimen, availability of a network of antiretroviral therapy providers, and strong desire among women for newer and more tolerable regimens. CONCLUSION: The transition to dolutegravir-based regimens has the potential to strengthen health systems in low- and middle-income countries to engender equitable access to optimised antiretroviral regimen among women. There is the need for a multi-sectoral effort to harness the opportunities of the health systems to addresses the bottlenecks to the transition and initiate extensive community engagement alongside individual and institutional capacity strengthening. Improvements in pregnancy pharmacovigilance and counselling and family planning services are critical to ensuring a successful transition among women of childbearing potential.

Dolutegravir versus efavirenz in women starting HIV therapy in late pregnancy (DolPHIN-2): an open-label, randomised controlled trial.

BACKGROUND: Late initiation of HIV antiretroviral therapy (ART) in pregnancy is associated with not achieving viral suppression before giving birth and increased mother-to-child transmission of HIV. We aimed to investigate virological suppression before giving birth with dolutegravir compared with efavirenz, when initiated during the third trimester. METHODS: In this randomised, open-label trial, DolPHIN-2, we recruited pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating ART in third trimester. Participants were randomly assigned (1:1) to dolutegravir-based or efavirenz-based therapy. HIV viral load was measured 7 days and 28 days after antiretroviral initiation, at 36 weeks' gestation, and at the post-partum visit (0-14 days post partum). The primary efficacy outcome was a viral load of less than 50 copies per mL at the first post-partum visit, and the primary safety outcome was the occurrence of drug-related adverse events in mothers and infants until the post-partum visit. Longer-term follow-up of mothers and infants continues. This study is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23, and Aug 15, 2018, we randomly assigned 268 mothers to dolutegravir (135) or efavirenz (133). All mothers and their infants were included in the safety analysis, and 250 mothers (125 in the dolutegravir group, 125 in the efavirenz group) and their infants in efficacy analyses, by intention-to-treat analyses. The median duration of maternal therapy at birth was 55 days (IQR 33-77). 89 (74%) of 120 in the dolutegravir group had viral loads less than 50 copies per mL, compared with 50 (43%) of 117 in the efavirenz group (risk ratio 1·64, 95% CI 1·31-2·06). 30 (22%) of 137 mothers in the dolutegravir group reported serious adverse events compared with 14 (11%) of 131 in the efavirenz group (p=0·013), particularly surrounding pregnancy and puerperium. We found no differences in births less than 37 weeks and less than 34 weeks gestation (16·4% vs 3·3%, across both groups). Three stillbirths in the dolutegravir group and one in the efavirenz group were considered unrelated to treatment. Three infant HIV infections were detected, all in the dolutegravir group, and were considered likely to be in-utero transmissions. INTERPRETATION: Our data support the revision to WHO guidelines recommending the transition to dolutegravir in first-line ART for all adults, regardless of pregnancy or child-bearing potential. FUNDING: Unitaid.

Acceptability, perceived reliability and challenges associated with distributing HIV self-test kits to young MSM in Uganda: a qualitative study.

INTRODUCTION: HIV self-testing is a flexible, accessible and acceptable emerging technology with a particular potential to identify people living with HIV who are reluctant to interact with conventional HIV testing approaches. We assessed the acceptability, perceived reliability and challenges associated with distributing HIV self-test (HIVST) to young men who have sex with men (MSM) in Uganda. METHODS: Between February and May, 2018, we enrolled 74 MSM aged ≥18 years purposively sampled and verbally consented to participate in six focus group discussions (FGDs) in The AIDS Support Organization (TASO Masaka and Entebbe). We also conducted two FGDs of 18 health workers. MSM FGD groups included individuals who had; (1) tested greater than one year previously; (2) tested between six months and one year previously; (3) tested three to six months previously; (4) never tested. FGDs examined: (i) the acceptability of HIVST distribution; (iii) preferences for various HIVST distribution channels; (iv) perceptions about the accuracy of HIVST; (v) challenges associated with HIVST distribution. We identified major themes, developed and refined a codebook. We used Nvivo version 11 for data management. RESULTS: MSM participants age ranged between 19 and 30 years. Participants described HIVST as a mechanism that would facilitate HIV testing uptake in a rapid, efficient, confidential, non-painful; and non-stigmatizing manner. Overall, MSM preferred HIVST to the conventional HIV testing approaches. Health workers were in support of distributing HIVST kits through MSM peers. MSM participants were willing to distribute the kits and recommended HIVST to their peers and sexual partners. They suggested HIVST kit distribution model work similarly to the current condom and lubricant peer model being implemented by TASO. Preferred channels were peers, hot spots, drop-in centres, private pharmacies and MSM friendly health facilities. Key concerns regarding use of HIVST were; unreliable HIVST results, social harm due to a positive result, need for a confirmatory test and linking both HIV positive and negative participants for additional HIV services. CONCLUSIONS: Distribution of HIVST kits by MSM peers is an acceptable strategy that can promote access to testing. HIVST was perceived by participants as beneficial because it would address many barriers that affect their acceptance of testing. However, a combined approach that includes follow-up, linkage to HIV care and prevention services are needed for effective results.

Describing the retention in care of human immunodeficiency virus-positive young adults who transition from adolescent to adult care.

Background: There is a high rate of lost to programme (LTP) in human immunodeficiency virus (HIV)-positive young adults transitioning from paediatric/adolescent to adult care. Methods: We describe and identify risk factors for LTP in all patients 18-23 y of age at the Infectious Diseases Institute (Kampala, Uganda) from 2010 to 2014. Results: A total of 260 of 907 young adults (28.6%) became LTP. Among those on antiretroviral treatment, 39.3% became LTP. We found that the only risk factor associated with LTP was being in World Health Organization stage 3 or 4. Conclusion: There is a need for tracing studies to evaluate the true vital status of LTP in this group.

Exploring attitudes and perceptions of patients and staff towards an after-hours co-pay clinic supplementing free HIV services in Kampala, Uganda.

BACKGROUND: There has been a rapid scale up of HIV services and access to anti-retroviral therapy in Africa over the last 10 years as a result of multilateral donor funding mechanisms. However, in order to continue to expand and to sustain these services it is important that "in country" options are explored. This study sought to explore attitudes and perceptions of people living with HIV (PLHIV) and health care staff towards using a fee-based "after hours" clinic (AHC) at the Infectious Diseases Institute (IDI) in Kampala, Uganda. METHODS: A cross-sectional study design, using qualitative methods for data collection was used. A purposeful sample of 188 adults including PLHIV accessing care at IDI and IDI staff were selected. We conducted 14 focus group discussions and 55 in-depth interviews. Thematic content analysis was conducted and Nvivo Software Version 10 was used to manage data. RESULTS: Findings suggested that some respondents were willing to pay for consultation, brand-name drugs, laboratory tests and other services. Many were willing to recommend the AHC to friends and/or relatives. However, there were concerns expressed of a risk that the co-pay model may lead to reduction in quality or provision of the free service. Respondents agreed that, as a sign of social responsibility, fees for service could help underprivileged patients. CONCLUSION: The IDI AHC clinic is perceived as beneficial to PLHIV because it provides access to HIV services at convenient times. Many PLHIV are willing to pay for this enhanced service. Innovations in HIV care delivery such as quality private-public partnerships may help to improve overall coverage and sustain quality HIV services in Uganda in the long term.