Oral PrEP uptake, adherence, and persistence during periconception periods among women in South Africa: an intervention study.

OBJECTIVE: We developed the Healthy Families-PrEP intervention to support HIV-prevention during periconception and pregnancy. We evaluated preexposure prophylaxis (PrEP) use with three objective measures. DESIGN: This single-arm intervention study enrolled women in KwaZulu-Natal, South Africa, who were HIV-uninfected, not pregnant, in a relationship with a partner with HIV or unknown-serostatus, and with pregnancy plans. PrEP was offered as part of a comprehensive HIV prevention intervention. Participants were followed for 12#$##x0200A;months. METHODS: We evaluated periconception PrEP uptake and adherence using quarterly plasma tenofovir concentrations. We modeled factors associated with PrEP uptake and high plasma tenofovir (past day dosing). Patterns of use were analyzed using electronic pillcap data. Dried blood spots to measure intracellular tenofovir product (past 2#$##x0200A;months dosing) were analyzed for a subset of women. RESULTS: Three hundred thirty women with median age 24 (IQR: 22#$#ndash;27) years enrolled. Partner HIV-serostatus was unknown by 96% (N#$##x0200A;#$#equals;#$##x0200A;316); 60% (195) initiated PrEP. High plasma tenofovir concentrations were seen in 35, 25, 22, and 20% of samples at 3, 6, 9, and 12#$##x0200A;months, respectively. Similar adherence was measured by pillcap and dried blood spots. In adjusted models, lower income, alcohol use, and higher HIV stigma were associated with high plasma tenofovir. Eleven HIV-seroconversions were observed (incidence rate: 4.04/100 person-years [95% confidence interval: 2.24#$#ndash;7.30]). None had detectable plasma tenofovir. CONCLUSION: The Healthy Families-PrEP intervention supported women in PrEP use. We observed high interest in periconception PrEP and over one-third adhered to PrEP in the first quarter; one-fifth were adherent over a year. High HIV incidence highlights the importance of strategies to reduce HIV incidence among periconception women. CLINICAL TRIAL NUMBER: NCT03194308.

Sexually Transmitted Infection Prevalence, Partner Notification, and Human Immunodeficiency Virus Risk Perception in a Cohort of Women Completing Sexually Transmitted Infection Screening as Part of a Safer Conception Study.

BACKGROUND: Integrating sexually transmitted infection (STI) and preexposure prophylaxis (PrEP) care may optimize sexual and reproductive health. METHODS: We nested an STI substudy within a human immunodeficiency virus (HIV) prevention cohort (parent study) of 18- to 35-year-old women from South Africa, planning pregnancy with a partner with HIV or of unknown serostatus. Parent-study women completed annual surveys regarding HIV-risk perceptions and were offered oral PrEP. Preexposure prophylaxis initiators completed quarterly plasma tenofovir (TFV) testing. Substudy women completed STI screening at enrollment, 6 months, onset of pregnancy, and in the third trimester via examination, vaginal swabs tested via PCR for Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis , Mycoplasma genitalium , and blood tested for Treponema pallidum . Follow-up was 6 months. Women with STIs were treated, offered partner notification (PN) cards, and surveyed regarding PN practices. We describe STI prevalence and incidence, and model factors associated with prevalent infection. Sexually transmitted infection substudy and parent study-only participants were matched on age and number of days on study to assess HIV-risk perception scores between the 2 groups and the proportion with detectable TFV. RESULTS: Among 50 substudy participants, 15 (30%) had prevalent STI. All 13 completing follow-up reported PN. Most did not prefer assisted PN. Mean HIV risk perception scores and proportion with detected plasma TFV were similar across groups. CONCLUSIONS: High STI prevalence supports the importance of laboratory screening to optimize sexual health for women planning pregnancy. Rates of self-reported PN are reassuring; low interest in assisted PN suggests the need for alternative approaches. Enhanced STI care did not affect HIV-risk perception or PrEP adherence, however both were relatively high in this cohort.

Social networks and HIV treatment adherence among people with HIV initiating treatment in rural Uganda and peri-urban South Africa.

Timely initiation of and adherence to antiretroviral therapy (ART) is critical for improving HIV outcomes and reducing HIV transmissibility. Social networks, or the social relationships individuals have with each other, have been linked with positive health outcomes, but less is known about the extent to which social network composition and structure are associated with improved ART adherence among people living with HIV (PLWH). We conducted an ego-centric network study among 828 previously ART-naïve PLWH presenting for ART initiation at 11 clinics in Mbarara, Uganda (rural population) and Gugulethu, South Africa (peri-urban population). We collected social network data using name generator and name interpreter questions. ART adherence was monitored over 12 months using wireless monitors (Wisepill). Our primary outcome of interest was ART adherence during the 12-month follow-up period. We used generalized linear models to estimate the associations between network measures and ART adherence. PLWH at the Uganda site (compared with the South Africa site) were less isolated, had larger social networks, and had more social ties providing sufficient social support; they were also more likely to bridge different social groups whereby not all social ties were connected to each other. In Uganda, social isolation was associated with a 5.5 percentage point reduction in ART adherence (95% confidence interval [CI] -9.95 to -1.13; p = 0.014), while having more same gender social ties was associated with higher ART adherence (b = 0.13, 95% CI 0.02-0.25, p = 0.025). In South Africa, there was no association between social isolation and ART adherence, and having more friendship ties (vs. family ties) was associated with lower ART adherence (b = -2.20, 95% CI -3.56 to -0.84; p = 0.002). Identifying and supporting PLWH who are isolated may facilitate optimal adherence, but understanding how networks differentially affect ART adherence by country context is important.

The feasibility, acceptability, and preliminary impact of real-time monitors and SMS on tuberculosis medication adherence in southwestern Uganda: Findings from a mixed methods pilot randomized controlled trial.

We conducted a pilot randomized controlled trial among patients initiating treatment for drug-sensitive tuberculosis (TB). Participants received real-time electronic adherence monitors and were randomized (1:1:1) to: (i) daily SMS (reminders to TB patients and notifications to social supporters sent daily for 3 months, then triggered by late or missed dosing for 3 months); (ii) weekly SMS (reminders to TB patients and notifications to social supporters sent weekly for 3 months, then triggered by late or missed dosing for 3 months); or (iii) control (no SMS). Feasibility was mainly verified by the technical function of the intervention at Month 6. The primary outcome was percent adherence as ascertained by the real time monitor. Quantitative feasibility/acceptability data were summarized descriptively. Percentage adherence and adherence patterns were assessed and compared by linear regression models. Qualitative acceptability data was collected through interviews and analyzed using content analysis. Among 63 participants, the median age was 35 years, 75% had no regular income, and 84% were living with HIV. Feasibility was demonstrated as most of the daily [1913/2395 (80%)] and weekly [631/872 (72%)] SMS reminders to TB patients were sent successfully. Also, most of the daily [1577/2395 (66%)] and weekly [740/872 (85%)] SMS notifications to social supporters and adherence data (96%) were sent successfully. Challenges included TB status disclosure, and financial constraints. All patients perceived the intervention to be useful in reminding and motivating them to take medication. Median adherence (IQR) in the daily SMS, weekly SMS, and control arms was 96.1% (84.8, 98.0), 92.5% (80.6, 96.3), and 92.2% (56.3, 97.8), respectively; however, differences between the intervention and control arms were not statistically significant. Real-time monitoring linked to SMS was feasible and acceptable and may have improved TB medication adherence. Larger studies are needed to further assess impact on adherence and clinical outcomes. Trial registration. ClinicalTrials.gov registration number: NCT03800888. https://ichgcp.net/clinical-trials-registry/NCT03800888.

Adherence to daily, oral TDF/FTC PrEP during periconception among HIV-exposed South African women.

Background: Daily, oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis (PrEP) reduces HIV acquisition for African women. Adherence is key to efficacy and patterns of adherence can be highly variable in real-world settings. Using group-based trajectory modeling (GBTM), we sought to identify distinct patterns of periconception PrEP adherence and evaluate potential baseline predictors of such adherence trajectories. Methods: We conducted a single-arm longitudinal study for women aged 18-35 years living in Durban, South Africa with personal or partner plans for pregnancy with a partner with HIV or of unknown serostatus. Participants were offered safer conception counseling, including daily oral PrEP; women who initiated PrEP were given a bottle with an electronic pillcap that recorded when device opens. Weekly adherence to daily PrEP was modeled using GBTM with a censored normal outcome distribution as a function of weeks since PrEP initiation. The number and functional form of the adherence trajectory groups were primarily selected based on Bayesian information criteria (BIC) and confirmed by mean estimated probabilities of group membership. A multivariable version of the selected model assessed baseline predictors of membership in adherence trajectory groups. Results: Overall mean (95% CI) adherence to PrEP was 63% (60%, 67%). We identified four groups of women with distinct patterns of adherence: (1) high (i.e., ≥6 doses per week) steady adherence throughout follow-up (22% of PrEP initiators); (2) moderate (i.e., 4-5 doses per week), but steady adherence (31%); (3) initially high, but consistently declining adherence (21%); and (4) initially moderate adherence, followed by a rapid decline and subsequent rebound (26%). In multivariable-adjusted analyses, older age was associated with membership in the high, steady adherence group as compared to the group identified with an adherence trajectory of initially high, then decline, and finally a rebound. Conclusions: GBTM is useful for exploring potential heterogeneity in longitudinal patterns of medication adherence. Although a large proportion of women in this study achieved high levels of adherence by electronic pillcap initially, far fewer women maintained these levels consistently. Knowledge of different adherence trajectories could be used to develop targeted strategies for optimizing HIV prevention during periconception.

Impact of Kaposi Sarcoma on Quality of Life Amongst HIV-infected Adults Initiating Antiretroviral Therapy in East Africa.

BACKGROUND: In sub-Saharan Africa, increased antiretroviral therapy (ART) availability has improved survival after diagnosis of Kaposi sarcoma (KS) compared to the pre-ART era, but mortality among patients with KS is still considerably higher than HIV-infected persons without KS. Furthermore, among those patients with KS who are treated initially with ART without adjunct chemotherapy and who do survive, little is known about how well they function and feel - quality of life (QOL) - compared to those without KS. METHODS: Among HIV-infected adults initiating ART in two prospective studies in Uganda, we compared those presenting with KS to those without KS. QOL was measured using the Medical Outcomes Survey-HIV instrument prior to ART initiation and at 16, 32, and 48 weeks thereafter; higher scores indicate better QOL. To ascertain the independent effect of KS versus non-KS on 11 domains of QOL and two summary scores, we created mixed effects models adjusted for directed acyclic graph-informed confounders. RESULTS: We examined 224 participants with KS and 730 without KS, among whom 64% were women and median age was 34 years. Prior to ART initiation, participants had a median CD4+ T count of 159 cells/mm3 and plasma HIV RNA of 5.1 log10 copies/ml. In adjusted analyses prior to ART initiation, those with KS had lower mean scores in 8 of 11 QOL domains and both physical and mental health summary scores compared to those without KS. After 48 weeks of ART, those with KS had higher mean QOL scores compared those without KS in 4 domains and the mental health summary score, and lower scores in only one domain. There was no significant difference in 6 domains and the physical health summary score. CONCLUSIONS: Amongst HIV-infected adults in East Africa, at time of ART initiation, those with KS had worse mean QOL compared to those without KS. Over the first year of ART, those with KS became comparable to or exceeded those without KS in most QOL domains. The findings indicate that some patients with KS can be treated with ART alone and further emphasize the need to predict those who will do well with ART alone versus those who need additional initial therapy.

Maternal adverse childhood experiences, child mental health, and the mediating effect of maternal depression: A cross-sectional, population-based study in rural, southwestern Uganda.

OBJECTIVES: This study aimed to examine the intergenerational effects of maternal adverse childhood experiences (ACEs) and child mental health outcomes in rural Uganda, as well as the potentially mediating role of maternal depression in this pathway. Additionally, we sought to test the extent to which maternal social group membership attenuated the mediating effect of maternal depression on child mental health. METHODS: Data come from a population-based cohort of families living in the Nyakabare Parish, a rural district in southwestern Uganda. Between 2016 and 2018, mothers completed surveys about childhood adversity, depressive symptoms, social group membership, and their children's mental health. Survey data were analyzed using causal mediation and moderated-mediation analysis. RESULTS: Among 218 mother-child pairs, 61 mothers (28%) and 47 children (22%) showed symptoms meeting cutoffs for clinically significant psychological distress. In multivariable linear regression models, maternal ACEs had a statistically significant association with severity of child conduct problems, peer problems, and total child difficulty scores. Maternal depression mediated the relationship between maternal ACEs and conduct problems, peer problems, and total difficulty, but this mediating effect was not moderated by maternal group membership. CONCLUSIONS: Maternal depression may act as a potential mechanism linking maternal childhood adversity with poor child mental health in the next generation. Within a context of elevated rates of psychiatric morbidity, high prevalence of childhood adversity, and limited healthcare and economic infrastructures across Uganda, these results emphasize the prioritization of social services and mental health resources for rural Ugandan families.

Factors Associated With Changes in Alcohol Use During Pregnancy and the Postpartum Transition Among People With HIV in South Africa and Uganda.

Identifying factors associated with alcohol use changes during pregnancy is important for developing interventions for people with HIV (PWH). Pregnant PWH (n = 202) initiating antiretroviral therapy in Uganda and South Africa completed two assessments, 6 months apart (T1, T2). Categories were derived based on AUDIT-C scores: "no use" (AUDIT-C = 0 at T1 and T2), "new use" (AUDIT-C = 0 at T1, >0 at T2), "quit" (AUDIT-C > 0 at T1, =0 at T2), and "continued use" (AUDIT-C > 0, T1 and T2). Factors associated with these categories were assessed. Most participants had "no use" (68%), followed by "continued use" (12%), "quit" (11%), and "new use" (9%). Cohabitating with a partner was associated with lower relative risk of "continued use." Borderline significant associations between food insecurity and higher risk of "new use" and between stigma and reduced likelihood of "quitting" also emerged. Alcohol use interventions that address partnership, food security, and stigma could benefit pregnant and postpartum PWH.

High PrEP uptake and objective longitudinal adherence among HIV-exposed women with personal or partner plans for pregnancy in rural Uganda: A cohort study.

BACKGROUND: In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. Pre-exposure prophylaxis (PrEP) reduces HIV acquisition for women and, therefore, infants. We developed the Healthy Families-PrEP intervention to support PrEP use as part of HIV prevention during periconception and pregnancy periods. We conducted a longitudinal cohort study to evaluate oral PrEP use among women participating in the intervention. METHODS AND FINDINGS: We enrolled HIV-negative women with plans for pregnancy with a partner living, or thought to be living, with HIV (2017 to 2020) to evaluate PrEP use among women participating in the Healthy Families-PrEP intervention. Quarterly study visits through 9 months included HIV and pregnancy testing and HIV prevention counseling. PrEP was provided in electronic pillboxes, providing the primary adherence measure ("high" adherence when pillbox was opened ≥80% of days). Enrollment questionnaires assessed factors associated with PrEP use. Plasma tenofovir (TFV) and intraerythrocytic TFV-diphosphate (TFV-DP) concentrations were determined quarterly for women who acquired HIV and a randomly selected subset of those who did not; concentrations TFV ≥40 ng/mL and TFV-DP ≥600 fmol/punch were categorized as "high." Women who became pregnant were initially exited from the cohort by design; from March 2019, women with incident pregnancy remained in the study with quarterly follow-up until pregnancy outcome. Primary outcomes included (1) PrEP uptake (proportion who initiated PrEP); and (2) PrEP adherence (proportion of days with pillbox openings during the first 3 months following PrEP initiation). We used univariable and multivariable-adjusted linear regression to evaluate baseline predictors selected based on our conceptual framework of mean adherence over 3 months. We also assessed mean monthly adherence over 9 months of follow-up and during pregnancy. We enrolled 131 women with mean age 28.7 years (95% CI: 27.8 to 29.5). Ninety-seven (74%) reported a partner with HIV and 79 (60%) reported condomless sex. Most women (N = 118; 90%) initiated PrEP. Mean electronic adherence during the 3 months following initiation was 87% (95% CI: 83%, 90%). No covariates were associated with 3-month pill-taking behavior. Concentrations of plasma TFV and TFV-DP were high among 66% and 47%, 56% and 41%, and 45% and 45% at months 3, 6, and 9, respectively. We observed 53 pregnancies among 131 women (1-year cumulative incidence 53% [95% CI: 43%, 62%]) and 1 HIV-seroconversion in a non-pregnant woman. Mean pillcap adherence for PrEP users with pregnancy follow-up (N = 17) was 98% (95% CI: 97%, 99%). Study design limitations include lack of a control group. CONCLUSIONS: Women in Uganda with PrEP indications and planning for pregnancy chose to use PrEP. By electronic pillcap, most were able to sustain high adherence to daily oral PrEP prior to and during pregnancy. Differences in adherence measures highlight challenges with adherence assessment; serial measures of TFV-DP in whole blood suggest 41% to 47% of women took sufficient periconception PrEP to prevent HIV. These data suggest that women planning for and with pregnancy should be prioritized for PrEP implementation, particularly in settings with high fertility rates and generalized HIV epidemics. Future iterations of this work should compare the outcomes to current standard of care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03832530 https://clinicaltrials.gov/ct2/show/NCT03832530?term=lynn+matthews&cond=hiv&cntry=UG&draw=2&rank=1.

'I still desire to have a child': a qualitative analysis of intersectional HIV- and childlessness-related stigma in rural southwestern Uganda.

This study explored the intersecting forms of stigma experienced by HIV-serodifferent couples with unmet reproductive goals in rural Uganda. The parent mixed-methods study, which included 131 HIV-exposed women with plans for pregnancy, offered comprehensive HIV prevention counselling and care over a nine-month period. In-depth interviews were conducted with 37 women and seven male partners to explore care experiences and the use of safer conception strategies. This secondary analysis explored how challenges conceiving informed pregnancy plans and HIV prevention behaviours. The following themes were developed (1) partnership conflicts arise from HIV- and infertility-related forms of stigma, contributing to gender-based violence, partnership dissolution and the pursuit of new partners; (2) cultural and gender norms pressure men and women to conceive and maintain partnerships, which is complicated by the stigma directed towards serodifferent couples; (3) frustration with low partner participation in safer conception strategies led to the decreased use of these methods of HIV prevention; (4) health care provider support promotes continued hope of conception and helps overcome stigma. In HIV-affected partnerships, these intersecting forms of stigma may impact HIV prevention. Seeking to fulfil their reproductive needs, partners may increase HIV transmission opportunities as they engage in condomless sex with additional partners and decrease adherence to prevention strategies. Future research programmes should consider the integration of fertility counselling with reproductive and sexual health care.

Optimizing PMTCT Adherence by Treating Depression in Perinatal Women with HIV in South Africa: A Pilot Randomized Controlled Trial.

BACKGROUND: South Africa (SA) has the greatest HIV prevalence in the world, with rates as high as 40% among pregnant women. Depression is a robust predictor of nonadherence to antiretroviral therapy (ART) and engagement in HIV care; perinatal depression may affect upwards of 47% of women in SA. Evidence-based, scalable approaches for depression treatment and ART adherence in this setting are lacking. METHOD: Twenty-three pregnant women with HIV (WWH), ages 18-45 and receiving ART, were randomized to a psychosocial depression and adherence intervention or treatment as usual (TAU) to evaluate intervention feasibility, acceptability, and preliminary effect on depressive symptoms and ART adherence. Assessments were conducted pre-, immediately post-, and 3 months post-treatment, and included a qualitative exit interview. RESULTS: Most (67.6%) eligible individuals enrolled; 71% completed at least 75% of sessions. Compared to TAU, intervention participants had significantly greater improvements in depressive symptoms at post-treatment, ß = - 11.1, t(24) = - 3.1, p < 0.005, 95% CI [- 18.41, - 3.83], and 3 months, ß = - 13.8, t(24) = - 3.3, p < 0.005, 95% CI [- 22.50, - 5.17]. No significant differences in ART adherence, social support, or stigma were found. Qualitatively, perceived improvements in social support, self-esteem, and problem-solving adherence barriers emerged as key benefits of the intervention; additional sessions were desired. CONCLUSION: A combined depression and ART adherence intervention appears feasible and acceptable, and demonstrated preliminary evidence of efficacy in a high-need population. Additional research is needed to confirm efficacy and identify dissemination strategies to optimize the health of WWH and their children. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03069417. Protocol available at https://clinicaltrials.gov/ct2/show/NCT03069417.

Cigarette smoking and misperceived norms among adults in rural Uganda: a population-based study.

BACKGROUND: Little is known about perceived norms about cigarette smoking in Uganda or the extent to which perceptions drive personal cigarette smoking behaviour. METHODS: We conducted a cross-sectional study in 2016-2018 that targeted all adults who resided within eight villages in Rwampara District, southwestern Uganda. Personal cigarette smoking frequency was elicited by self-report. We also asked participants what they believed to be the cigarette smoking frequency of most other adult men and women in their villages (i.e., perceived norms). Frequent cigarette smoking was defined as 4+ times/week. We compared perceived norms to cigarette smoking frequency reports aggregated at the village level. We used multivariable Poisson regression to estimate the association between perceived norms and personal cigarette smoking behaviour. RESULTS: Among 1626 participants (91% response rate), 92 of 719 men (13%) and 6 of 907 women (0.7%) reported frequent smoking. However, 1030 (63%) incorrectly believed most men in their villages smoked cigarettes frequently. Additionally, 116 (7%) incorrectly believed that most women in their villages smoked cigarettes frequently. These misperceptions were pervasive across social strata. Men who misperceived frequent cigarette smoking as the norm among other men in their villages were more likely to smoke frequently themselves (adjusted relative risk=1.49; 95% CI, 1.13 to 1.97). CONCLUSIONS: Most adults overestimated cigarette smoking frequency among village peers. Men who incorrectly believed that frequent smoking was the norm were more likely to engage in frequent smoking themselves. Applying a 'social norms approach' intervention by promoting existing healthy norms may prevent smoking initiation or motivate reductions in smoking among men in rural Uganda.

Social network correlates of free and purchased insecticide-treated bed nets in rural Uganda.

BACKGROUND: Malaria is a major cause of mortality and morbidity in Uganda. Despite Uganda's efforts to distribute bed nets, only half of households have achieved the World Health Organization (WHO) Universal Coverage Criteria (one bed net for every two household members). The role of peer influence on bed net ownership remains underexplored. Data on the complete social network of households were collected in a rural parish in southwestern Uganda to estimate the association between household bed net ownership and peer household bed net ownership. METHODS: Data on household sociodemographics, bed net ownership, and social networks were collected from all households across one parish in southwestern Uganda. Bed nets were categorized as either purchased or free. Purchased and free bed net ownership ratios were calculated based on the WHO Universal Coverage Criteria. Using network name generators and complete census of parish residents, the complete social network of households in the parish was generated. Linear regression models that account for network autocorrelation were fitted to estimate the association between households' bed net ownership ratios and bed net ownership ratios of network peer households, adjusting for sociodemographics and network centrality. RESULTS: One thousand seven hundred forty-seven respondents were interviewed, accounting for 716 households. The median number of peer households to which a household was directly connected was 7. Eighty-six percent of households owned at least one bed net, and 41% of households met the WHO Universal Coverage Criterion. The median bed net ownership ratios were 0.67 for all bed nets, 0.33 for free bed nets, and 0.20 for purchased bed nets. In adjusted multivariable models, purchased bed net ownership ratio was associated with average household wealth among peer households (b = 0.06, 95% CI 0.03, 0.10), but not associated with average purchased bed net ownership ratio of peer households. Free bed net ownership ratio was associated with the number of children under 5 (b = 0.08, 95% CI 0.05, 0.10) and average free bed net ownership ratios of peer households (b = 0.66, 95% CI 0.46, 0.85). CONCLUSIONS: Household bed net ownership was associated with bed net ownership of peer households for free bed nets, but not for purchased bed nets. The findings suggest that public health interventions may consider leveraging social networks as tools for dissemination, particularly for bed nets that are provided free of charge.

STI prevalence, incidence, and partner notification among women in a periconception HIV prevention program in Uganda.

BACKGROUND: We provided sexually transmitted infection (STI) screening and facilitated partner notification and treatment among women participating in a periconception HIV prevention program in southwestern Uganda to understand follow-up STI incidence. METHODS: Women at-risk for HIV exposure while planning for pregnancy completed laboratory screening for chlamydia, gonorrhea, trichomoniasis, and syphilis at enrollment and 6 months of follow-up and/or incident pregnancy; facilitated partner notification and treatment were offered for those with positive tests. We performed a logistic regression to determine correlates of follow-up STI. RESULTS: Ninety-four participants completed enrollment STI screening with a median age of 29 (IQR 26-34); 23 (24%) had ≥1 STI. Of the 23 participants with enrollment STI(s), all completed treatment and 19 (83%) returned for follow-up; 18 (78%) reported delivering partner notification cards and discussing STIs with partner(s), and 14 (61%) reported all partners received STI treatment. Of the 81 (86%) who successfully completed follow-up STI screening, 17 (21%) had ≥1 STI. The STI incidence rate was 29.0 per 100 person-years. In univariable regression analysis, enrollment STI, younger age, less education, and alcohol consumption were all significantly associated with follow-up STI. CONCLUSIONS: We demonstrated high enrollment and follow-up STI rates and moderate participant-reported partner treatment among women planning for pregnancy in Uganda despite partner notification and treatment. Novel STI partner notification and treatment interventions are needed to decrease the STI burden, especially among women planning for and with pregnancy.

Demonstration and Acceptability of a Safer Conception Intervention for Men With HIV in South Africa: Pilot Cohort Study.

BACKGROUND: Many men with HIV (MWH) want to have children. HIV viral suppression minimizes sexual HIV transmission risks while allowing for conception and optimization of the health of men, their partners, and their infants. OBJECTIVE: This study developed and evaluated the feasibility and acceptability of an intervention to promote serostatus disclosure, antiretroviral therapy (ART) uptake and adherence, and viral suppression among MWH who want to have children in South Africa. METHODS: We developed a safer conception intervention (Sinikithemba Kwabesilisa or We give hope to men) to promote viral suppression via ART uptake and adherence, HIV serostatus disclosure, and other safer conception strategies for MWH in South Africa. Through 3 counseling and 2 booster sessions over 12 weeks, we offered education on safer conception strategies and aided participants in developing a safer conception plan. We recruited MWH (HIV diagnosis known for >1 month), not yet accessing ART or accessing ART for <3 months, in a stable partnership with an HIV-negative or unknown-serostatus woman, and wanting to have a child in the following year. We conducted an open pilot study to evaluate acceptability based on patient participation and exit interviews and feasibility based on recruitment and retention. In-depth exit interviews were conducted with men to explore intervention acceptability. Questionnaires collected at baseline and exit assessed disclosure outcomes; CD4 and HIV-RNA data were used to evaluate preliminary impacts on clinical outcomes of interest. RESULTS: Among 31 eligible men, 16 (52%) enrolled in the study with a median age of 29 (range 27-44) years and a median time-since-diagnosis of 7 months (range 1 month to 9 years). All identified as Black South African, with 56% (9/16) reporting secondary school completion and 44% (7/16) reporting full-time employment. Approximately 44% (7/16) of participants reported an HIV-negative (vs unknown-serostatus) partner. Approximately 88% (14/16) of men completed the 3 primary counseling sessions. In 11 exit interviews, men reported personal satisfaction with session content and structure while also suggesting that they would refer their peers to the program. They also described the perceived effectiveness of the intervention and self-efficacy to benefit. Although significance testing was not conducted, 81% (13/16) of men were taking ART at the exit, and 100% (13/13) of those on ART were virally suppressed at 12 weeks. Of the 16 men, 12 (75%) reported disclosure to pregnancy partners. CONCLUSIONS: These preliminary data suggest that safer conception care is acceptable to men and has the potential to reduce HIV incidence among women and their children while supporting men's health. Approximately half of the men who met the screening eligibility criteria were enrolled. Accordingly, refinement to optimize uptake is needed. Providing safer conception care and peer support at the community level may help reach men. TRIAL REGISTRATION: ClinicalTrials.gov NCT03818984; https://clinicaltrials.gov/ct2/show/NCT03818984. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-https://doi.org/10.1007/s10461-017-1719-4.

A qualitative study of the acceptability of remote electronic bednet use monitoring in Uganda.

BACKGROUND: Distribution of long-lasting insecticide treated nets (LLINs) is the most widely used intervention for the prevention of malaria but recall and social desirability biases may lead to challenges in accurately measuring use of bednets. SmartNet is a remote electronic monitor that provides objective measurements of bednet use over weeks at a time. Assessing local acceptability is important when implementing innovative global health technologies such as SmartNet. This study draws on established models such as the Technology Acceptance Model (TAM) and Theoretical Framework of Acceptability (TFA) to assess acceptability of SmartNet in Ugandan households. METHODS: Semi-structured qualitative interviews were conducted at weeks one and six following installation of SmartNet in ten households in Western Uganda. Heads-of-households answered open-ended questions addressing the main acceptability domains of the TFA and TAM models (i.e. perceived ease of use, ethicality, etc.). Responses were digitally recorded, transcribed, coded and analyzed using a thematic analysis approach. RESULTS: Seven out of ten households interviewed reported no difference in use between SmartNet and a standard LLIN. Households stated the large size, soft fabric, and the efficacy of SmartNet relative to a standard LLIN contributed to perceived usefulness and perceived ease of use. Opportunity costs of the novel monitoring system expressed by households included difficulty washing nets and dislike of blinking lights on the device. Barriers to SmartNet use focused on questions of the ethics of bednet use monitoring, discomfort with technical aspects of the device and a poor understanding of its function amongst others in the community. However, explaining SmartNet to other community members resolved these concerns and often resulted in interest and acceptance among peers. CONCLUSION: Objective monitoring of bednet use with SmartNet appears acceptable to these households in Uganda. Use of SmartNet seems to be similar to behaviors around use of standard LLINs. Viewpoints on many aspects of SmartNet were generally favorable. Concerns around ethicality of bednet monitoring are present and indicate the need for continuing community education. The device will continue to be optimized to make it more acceptable to users and to accurately reflect standard LLIN use to improve our understanding of prevention behaviors in malaria endemic settings.

Adverse childhood experiences, alcohol consumption, and the modifying role of social participation: population-based study of adults in southwestern Uganda.

Background: Adverse childhood experiences (ACEs) include multiple forms of child maltreatment, including abuse and neglect, as well as other forms of household dysfunction. Studies from Uganda have revealed a high prevalence of child abuse, as well as one of the highest levels of alcohol consumption in Africa. Few population-based studies from Africa have estimated associations between ACEs and adult alcohol use, or assessed the potential buffering effects of social participation. Methods: This cross-sectional, population-based study was conducted in a rural parish in southwestern Uganda between 2016 and 2018. We assessed self-reported ACEs using a modified version of the Adverse Childhood Experiences - International Questionnaire (ACE-IQ) scale. We measured heavy alcohol consumption using a 3-item scale previously validated in this population. We measured social participation using a 10-item scale eliciting participants' membership and participation in different community groups over the past two months. We fitted multivariable Poisson regression models to estimate the associations between ACEs and heavy alcohol consumption, and to assess for the potential buffering effects of social participation. Results: We estimated statistically significant associations between the total ACE score and heavy alcohol consumption (adjusted relative risk [ARR] per ACE=1.17; 95% CI, 1.09-1.25; P ≤0.001). Social participation had a statistically significant moderating effect on the association between total ACE score and heavy alcohol consumption (P=0.047 for interaction): the estimated association between total ACE score and heavy alcohol consumption among study participants who did not participate in a community group was larger, with a narrower confidence interval (ARR=1.21 per ACE; 95% CI, 1.11-1.33; P<0.001), while the estimated association among study participants who did participate in a community group was smaller and less precisely estimated (ARR=1.12 per ACE; 95% CI, 1.02-1.24; P=0.02). Conclusions: Our findings demonstrate an association between ACEs and heavy alcohol consumption behavior among adults in rural Uganda. The adverse effects of ACEs were buffered in part by social participation. To prevent or reduce harmful alcohol use behaviors among adults, it is important to address the chronic stress caused by ACEs.

A qualitative exploration to understand barriers and facilitators to daily oral PrEP uptake and sustained adherence among HIV-negative women planning for or with pregnancy in rural Southwestern Uganda.

INTRODUCTION: Antiretroviral pre-exposure prophylaxis (PrEP) may reduce periconception and pregnancy HIV incidence among women in settings, where gender power imbalances limit HIV testing, engagement in care and HIV viral suppression. We conducted qualitative interviews to understand factors influencing periconception and pregnancy PrEP uptake and use in a cohort of women (Trial registration: NCT03832530) offered safer conception counselling in rural Southwestern Uganda, where PrEP uptake was high. METHODS: Between March 2018 and January 2019, in-depth interviews informed by conceptual frameworks for periconception risk reduction and PrEP adherence were conducted with 37 women including those with ≥80% and <80% adherence to PrEP doses measured by electronic pill cap, those who never initiated PrEP, and seven of their male partners. Content and dyadic analyses were conducted to identify emergent challenges and facilitators of PrEP use within individual and couple narratives. RESULTS: The median age for women was 33 years (IQR 28, 35), 97% felt likely to acquire HIV and 89% initiated PrEP. Individual-level barriers included unwillingness to take daily pills while healthy, side effects and alcohol use. Women overcame these barriers through personal desires to have control over their HIV serostatus, produce HIV-negative children and prevent HIV transmission within partnerships. Couple-level barriers included nondisclosure, mistrust and gender-based violence; facilitators included shared goals and perceived HIV protection, which improved communication, sexual intimacy and emotional support within partnerships through a self-controlled method. Community-level barriers included multi-level stigma related to HIV, ARVs/PrEP and serodifference; facilitators included active peer, family or healthcare provider support as women aspired to safely meet socio-cultural expectations to conceive and preserve serodifferent relationships. Confidence in PrEP effectiveness was promoted by positive peer experiences with PrEP and ongoing HIV testing. CONCLUSIONS: Multi-level forms of HIV-, serodifference- and disclosure-related stigma, side effects, pill burden, alcohol use, relationship dynamics, social, professional and partnership support towards adaptation and HIV risk reduction influence PrEP uptake and adherence among HIV-negative women with plans for pregnancy in rural Southwestern Uganda. Confidence in PrEP, individually controlled HIV prevention and improved partnership communication and intimacy promoted PrEP adherence. Supporting individuals to overcome context-specific barriers to PrEP use may be an important approach to improving uptake and prolonged use.

Perceptions About Local ART Adherence Norms and Personal Adherence Behavior Among Adults Living with HIV in Rural Uganda.

Although misperceived norms often drive personal health behaviors, we do not know about this phenomenon in the context of antiretroviral therapy (ART) adherence. We conducted a cross-sectional study including all persons living with HIV (PLWH) on ART across eight villages in one parish in a rural region of southwestern Uganda. We used surveys to measure personal reports of ART adherence (not missing any doses of ART in the past 7 days was considered optimal adherence whereas missing doses was considered suboptimal adherence) and perceived norms about the local ART adherence norm (whether or not each individual thought 'most other PLWH on ART in this parish' missed any doses in the past 7 days). Multivariable Poisson regression models were used to estimate the association between perceived norms and personal adherence. Among 159 PLWH on ART (95% response rate), 142 (89%) reported no missed doses. However, 119 (75%) thought most individuals in this population of PLWH on ART were sub-optimally adherent. This misperception about the local ART adherence norm was prevalent in every subgroup of PLWH. Misperceiving the local ART adherence norm to be sub-optimal adherence was associated with a reduced likelihood of optimal adherence among married PLWH (adjusted relative risk [aRR] = 0.83; 95% confidence interval [CI] 0.71-0.97). The association was similar but imprecisely estimated for all PLWH (aRR = 0.91; 95% CI 0.82-1.01). Interventions to correct misperceived ART adherence norms as a stand-alone intervention or as a complement to other adherence promotion programs may influence ART adherence behavior and perhaps reduce HIV-related stigma.

RESUMEN: Aunque las normas mal percibidas impulsan los comportamientos personales de salud, no sabemos acerca de este fenómeno en el contexto de la terapia antirretroviral (TAR). Este estudio transversal incluyó a todas las personas que viven con el VIH (PVVS) y con TAR en ocho pueblos de una parroquia en una región rural del suroeste de Uganda. Utilizamos encuestas para medir los informes de adherencia personal al TAR (no faltar ninguna dosis de TAR en los últimos 7 días se consideró como acción óptima; mientras que faltar las dosis se consideraron como acción subóptima) y las normas percibidas sobre la norma local de adherencia al TAR (si cada individuo pensó o no que 'la mayoría de las otras PVVS en esta parroquia omitieron alguna dosis en los últimos 7 días). Usamos modelos multivariables de regresión de Poisson para estimar la asociación entre las normas percibidas y la adherencia personal. De las 159 PVVS con TAR (tasa de respuesta del 95%), 142 (89%) reportaron que no faltaron ningua dosis. Sin embargo, 119 (75%) pensaron que la mayoría de los individuos en esta población de PVVS con TAR eran suboptimalmente adherentes. Esta percepción incorrecta sobre la norma local de adherencia al TAR fue prevalente en todos los subgrupos de PVVS. La percepción incorrecta de que la norma local de adherencia al TAR era subóptima se asoció con una menor probabilidad de adherencia óptima entre las PVVS casadas (riesgo relativo ajustado [aRR] = 0,83; intervalo de confianza [IC] del 95% 0,71-0,97). La asociación fue similar pero imprecisamente se estima para todas las PVVS (aRR = 0,91; IC 95% 0,82-1,01). Las intervenciones para corregir las normas mal percibidas de TAR, como una intervención independiente o como un complemento de otros programas de promoción de la adherencia, pueden influir en el comportamiento de la adherencia al TAR y tal vez reducir el estigma relacionado con el VIH.

High residual inflammation despite HIV viral suppression: Lessons learned from real-time adherence monitoring among people with HIV in Africa.

BACKGROUND: Lower antiretroviral therapy (ART) adherence is associated with higher systemic inflammation in virally suppressed people with HIV (PWH); however, previous studies have mostly relied on subjective adherence measures and have not assessed this association by disease stage upon ART initiation. METHODS: In the Monitoring Early Treatment Adherence study, adherence was monitored electronically in real time among adult, treatment-naïve PWH in Uganda and South Africa who initiated tenofovir disoproxil fumarate/emtricitabine/efavirenz during early-stage (CD4 > 350 cells/µL) or late-stage (CD4 < 200 cells/µL) disease. Participants who achieved viral suppression (< 400 copies/mL) at 6 months and remained suppressed after 12 months were analysed. The association between average ART adherence and plasma concentrations of interleukin 6 (IL-6), soluble CD14 (sCD14) and D-dimer was evaluated using adjusted multivariable linear regression, stratified by disease stage. RESULTS: In all, 488 PWH (61% women, mean age 35 years) were included in the analysis. Median ART adherence overall was 87%. In adjusted models, every 10% increase in average adherence was associated with a 3.0% decrease in IL-6 [95% confidence interval (CI): -5.9 to -0.01, p = 0.05] at 12 months. This relationship was observed in PWH with both early-stage (5.9%, 95% CI: -10.1 to -1.6, p = 0.009) and late-stage disease (3.7%, 95% CI: -7.2 to -0.2, p = 0.039). No significant associations were found with sCD14 or D-dimer. CONCLUSIONS: Objective ART adherence measurement was inversely associated with systemic inflammation in PWH who achieved viral suppression after ART initiation in sub-Saharan Africa, with a greater association in those with early-stage HIV. This finding underscores the importance of ART adherence beyond establishing viral suppression.