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Introduction: In people living with HIV, adherence to antiretroviral therapy (ART) is essential for achieving and sustaining viral suppression and reducing mortality. In young people living with HIV, ART adherence and retention remain a challenge with unsatisfactory viral suppression rates despite facility-based intensive adherence counseling that is the standard of care. Few studies have evaluated mHealth adherence interventions among young people living with HIV in resource-limited settings., Methods: This was a randomized parallel trial. Young people aged between15-24 living with HIV, initiating ART, or on ART for not more than 6 months at three ART clinics were recruited and randomized to a ratio of 1:1 to either standard of care or the intervention "Call for Life-Interactive Voice Response" with standard of care, between 12th August 2020 and 1st June 2022. The intervention is mobile technology-based software, that has interactive voice response functionalities, with a web-based interface, that allows interaction through the use of voice and tones via a dial pad. The primary outcome was viral suppression defined as HIV RNA below 1,000 copies per mL at 12 months with retention in care and viral suppression at month 6 as a secondary outcome. Descriptive statistics were used for participant characteristics. Primary outcomes and factors associated with viral load failure were assessed using the log-binomial model. All calculations were done using statistical software release 16.0., Results: A total of 206 participants were recruited and randomized; the mean age was 22.5(SD±1.9) years and 81% (167/206) were female. The intervention had 78.6% (81/103), females, while the standard of care had 83.5% (86/103). Viral suppression at 12 months in the intervention arm was 73.6% (67/91) versus 51.9% (40/77) in the standard of care arm, p=0.01. Retention in care was 88.4% (91/103) in the intervention vs. 74.7% (77/103) in the standard of care arm p=0.01., Conclusion: This is the first study in Uganda to demonstrate that mHealth has the potential to improve medication adherence and retention in care among youth living with HIV in Uganda., Trial Registration: NCT04718974 Registry: clinical Trials.gov., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RPR discloses that Infectious Diseases Institute received funds from Janssen, the Pharmaceutical Companies of Johnson and Johnson for Call for Life Projects and other Project Research., (Copyright: © 2024 Bwanika Naggirinya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years., Methods: We conducted a qualitative study from February 2022 to March 2023, at three paediatric and adolescent HIV treatment centers in Uganda. In-depth interviews were conducted at TPT initiation and after completion for purposively selected health workers, adolescents aged 10-19 years living with HIV, and caretakers of children aged below 18years., Results: The desire to avoid TB disease, previous TB treatment, encouragement from family members, and ministry of health policies emerged as key facilitators for the children and adolescents to initiate TPT. Barriers to TPT initiation included; TB and HIV-related stigma, busy carer and adolescent work schedules, reduced social support from parents and family, history of drug side effects, high pill burden and fatigue, and perception of not being ill. TPT completion was enabled by combined TPT and ART refill visits, delivery of ART and TPT within the community, and continuous education and counseling from health workers. Reported barriers to TPT completion included TB and HIV-related stigma, long waiting time. Non-disclosure of HIV status by caretakers to CALHIV and fear of side effects was cited by health workers as a barrier to starting TPT. Facilitators of TPT initiation and completion reported by healthcare workers included patient and caretaker health education, counselling about benefits of TPT and risk of TB disease, having same appointment for TPT and ART refill to reduce patient waiting time, adolescent-friendly services, and appointment reminder phone calls., Conclusion: The facilitators and barriers of TPT initiation and completion among CALHIV span from individual, to health system and structural factors. Health education about benefits of TPT and risk of TB, social support, adolescent-friendly services, and joint appointments for TPT and ART refill are major facilitators of TPT initiation and completion among CALHIV in Uganda., (© 2024. The Author(s).)

Climate change is increasing the likelihood of drought in sub-Saharan Africa, where HIV prevalence is high. Drought could increase HIV transmission through various mediating mechanisms; we investigated these associations. We used data on people aged 15-59 from Population-Based HIV Impact Assessment surveys from 2016 in Eswatini, Lesotho, Tanzania, Uganda, and Zambia. Survey data were geospatially linked to precipitation data for 2014-2016, with local droughts defined as cumulative rainfall between 2014 and 2016 being in < 15th percentile of all 2-year periods over 1981-2016. Using multivariable logistic regression, stratified by sex and rural/urban residence, we examined associations between (a) drought and poverty, (b) wealth quintiles and sexual behaviours (transactional, high-risk, and intergenerational sex), (c) sexual behaviours and recently acquiring HIV, and (d) drought and recent HIV. Among 102,081 people, 31.5% resided in areas affected by drought during 2014-2016. Experiencing drought was positively associated with poverty for women and men in rural, but not urban, areas. For each group, increasing wealth was negatively associated with transactional sex. For rural women, intergenerational sex was positively associated with wealth. Women reporting each sexual behaviour had higher odds of recent HIV, with strong associations seen for high-risk sex, and, for urban women, intergenerational sex, with weaker associations among men. Women in rural areas who had been exposed to drought had higher odds of having recently acquired HIV (2.10 [95%CI: 1.17-3.77]), but not women in urban areas, or men. Droughts could potentially increase HIV transmission through increasing poverty and then sexual risk behaviours, particularly among women in rural areas., (© 2024. The Author(s).)

Objective: To evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery models in sub-Saharan Africa (SSA)., Design: Systematic review and meta-analysis., Data Sources: We searched online databases (PubMed, MEDLINE, SCOPUS, EMBASE, Google Scholar, Cochrane Database of Systematic Reviews and Web of Science) between January 2012 and 3 April 2022., Eligibility Criteria for Studies: Randomised controlled trials, cohort studies, cross-sectional studies and quasi-experimental studies with PrEP uptake, adherence and retention outcomes among FSWs in SSA., Data Extraction and Synthesis: Seven coders extracted data. The framework of the Cochrane Consumers and Communication Review Group guided data synthesis. The Risk of Bias In Non-Randomized Studies of Interventions tool was used to evaluate the risk of bias. Meta-analysis was conducted using a random-effects model. A narrative synthesis was performed to analyse the primary outcomes of PrEP uptake, adherence and retention., Results: Of 8538 records evaluated, 23 studies with 40 669 FSWs were included in this analysis. The pooled proportion of FSWs initiating PrEP was 70% (95% CI: 56% to 85%) in studies that reported on facility-based models and 49% (95% CI: 10% to 87%) in community-based models. At 6 months, the pooled proportion of FSWs retained was 66% (95% CI: 15% to 100%) for facility-based models and 83% (95% CI: 75% to 91%) for community-based models. Factors associated with increased PrEP uptake were visiting a sex worker programme (adjusted OR (aOR) 2.92; 95% CI: 1.91 to 4.46), having ≥10 clients per day (aOR 1.71; 95% CI: 1.06 to 2.76) and lack of access to free healthcare in government-run health clinics (relative risk: 1.16; 95% CI: 1.06 to 1.26)., Conclusions: A hybrid approach incorporating both facility-based strategies for increasing uptake and community-based strategies for improving retention and adherence may effectively improve PrEP coverage among FSWs., Prospero Registration Number: CRD42020219363., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Periods of droughts can lead to decreased food security, and altered behaviours, potentially affecting outcomes on antiretroviral therapy (ART) among persons with HIV (PWH). We investigated whether decreased rainfall is associated with adverse outcomes among PWH on ART in Southern Africa., Methods: Data were combined from 11 clinical cohorts of PWH in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, participating in the International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration. Adult PWH who had started ART prior to 01/06/2016 and were in follow-up in the year prior to 01/06/2016 were included. Two-year rainfall from June 2014 to May 2016 at the location of each HIV centre was summed and ranked against historical 2-year rainfall amounts (1981-2016) to give an empirical relative percentile rainfall estimate. The IeDEA-SA and rainfall data were combined using each HIV centre's latitude/longitude. In individual-level analyses, multivariable Cox or generalized estimating equation regression models (GEEs) assessed associations between decreased rainfall versus historical levels and four separate outcomes (mortality, CD4 counts < 200 cells/mm 3 , viral loads > 400 copies/mL, and > 12-month gaps in follow-up) in the two years following the rainfall period. GEEs were used to investigate the association between relative rainfall and monthly numbers of unique visitors per HIV centre., Results: Among 270,708 PWH across 386 HIV centres (67% female, median age 39 [IQR: 32-46]), lower rainfall than usual was associated with higher mortality (adjusted Hazard Ratio: 1.18 [95%CI: 1.07-1.32] per 10 percentile rainfall rank decrease) and unsuppressed viral loads (adjusted Odds Ratio: 1.05 [1.01-1.09]). Levels of rainfall were not strongly associated with CD4 counts < 200 cell/mm 3 or > 12-month gaps in care. HIV centres in areas with less rainfall than usual had lower numbers of PWH visiting them (adjusted Rate Ratio: 0.80 [0.66-0.98] per 10 percentile rainfall rank decrease)., Conclusions: Decreased rainfall could negatively impact on HIV treatment behaviours and outcomes. Further research is needed to explore the reasons for these effects. Interventions to mitigate the health impact of severe weather events are required., (© 2023. The Author(s).)

Background: We investigated the association between CYP2B6 polymorphisms and efavirenz drug resistance among women living with HIV who started on antiretroviral therapy during pregnancy and with high viremia during post-partum., Methods: This was a cross-sectional study of women with viral loads greater than 1000 copies/ml who were at least 6 weeks postpartum. Sanger sequencing was used to detect resistant mutations, as well as host genotyping, and efavirenz resistance was compared among the metabolizer genotypes., Results: Over the course of one year (July 2017-July 2018), 322 women were screened, with 110 (34.2%) having viral loads of 1000 copies/ml and 62 having whole blood available for genotyping. Fifty-nine of these women had both viral resistance and human host genotypic results. Efavirenz resistance according to metabolizer genotype was; 47% in slow, 34% in extensive and 28% in intermediate metabolizers, but the difference was not statistically significant due to the small sample size., Conclusions: There was no statistically significant difference in EFV resistance between EFV metabolizer genotypes in women who started antiretroviral therapy during pregnancy and had high viremia in the postpartum period. However, a numerical trend was discovered, which calls for confirmation in a large, well-designed, statistically powered study., (© 2023. The Author(s).)

Tuberculosis preventive therapy (TPT) effectively decreases rates of developing active tuberculosis disease in people living with HIV (PLHIV) who are at increased risk. The Uganda Ministry of Health launched a 100-day campaign to scale-up TPT in PLHIV in July 2019. We sought to examine the effect of the campaign on trends of TPT uptake and characteristics associated with TPT uptake and completion among persons in HIV care. We retrospectively reviewed routinely collected data from 2016 to 2019 at six urban public health facilities in Uganda. HIV care database and paper-based TPT registers at six public health facilities in Kampala, Uganda were retrospectively reviewed. Estimated trends of TPT (given as Isoniazid monotherapy) uptake and completion across the 4 years, among PLHIV aged 15 years and above, and factors associated, were examined using Poisson regression model with robust standard errors using generalized estimating equation (GEE) models. On average, a total of 39,774 PLHIV aged 15 years and above were eligible for TPT each calendar year at the six health facilities. Across all 4 years, more than 70% were females (range: 73.5% -74.6%) and the median age ranged from 33 to 34 years. From 2016 quarter one to 2019 quarter two, TPT uptake was consistently below 25%, but, as expected, the uptake significantly increased by about 3-folds from 22.1% to 61.2%, in 2019 quarter two (i.e. before the roll-out of the 100-day accelerated TPT intervention) and quarter three (i.e. after the roll-out of the 100-day accelerated TPT intervention) respectively. This increase remained highly significant even after adjusting for patients' baseline characteristics (adjusted prevalence ratio [aPR] = 2.58 [95%CI 2.45, 2.72], P-value<0.001). TPT completion was consistently high at above 70% at most of the time, but, it increased significantly among those initiated during 2018 quarter four and in the subsequent two quarters after the roll-out of the 100-day accelerated TPT intervention (i.e. TPT completion was: 83.2%, 95.3%, and 97.1% among individuals initiated during 2018 quarter4, and 2019 quarters 1 and 2, respectively). The increase in TPT completion during this period remained significant even after adjusting for patients' baseline characteristics (aPR [95%CI] = 1.09 [1.04, 1.14], P value<0.001, and 1.10 [1.05,1.15], P value<0.001, for individuals initiated during 2019 quarter 1, and 2, respectively compared to those initiated during 2018 quarter 4). Not on ART or newly started on ART compared to ART experienced, and pregnant at TPT initiation compared to not pregnant were associated with poor TPT completion, whereas older age (≥25 years versus 15-24 years) was associated with higher TPT completion. The targeted 100-day campaign dramatically increased TPT uptake and completion among PLHIV suggesting a viable catch up strategy to meet WHO guidelines. Future analysis with additional years of data post 100-days TPT intervention is required to evaluate the sustainability of the observed gains., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Musaazi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Key and priority populations (with risk behaviours and health inequities) are disproportionately affected by HIV in Uganda. We evaluated the impact of an intensive case management intervention on HIV treatment outcomes in Kalangala District, predominantly inhabited by fisher folk and female sex workers., Methods: This quasi-experimental pre-post intervention evaluation included antiretroviral therapy naïve adults aged ≥ 18 years from six health facilities in the pre-intervention (Jan 1, 2017-December 31, 2017) and intervention phase (June 13, 2018-June 30, 2019). The primary outcomes were 6-month retention and viral suppression (VS) before and after implementation of the intervention involving facility and community case managers who supported participants through at least the first three months of ART. We used descriptive statistics to compared the characteristics, overall outcomes (i.e., retention, lost to follow up, died), and VS of participants by phase, and used mixed-effects logistic regression models to determine factors associated with 6-month retention in care. Marginal (averaging over facilities) probabilities of retention were computed from the final multivariable model., Results: We enrolled 606 and 405 participants in the pre-intervention and intervention phases respectively. Approximately 75% of participants were aged 25-44 years, with similar age and gender distributions among phases. Approximately 46% of participants in the intervention were fisher folk and 9% were female sex workers. The adjusted probability of 6-month retention was higher in the intervention phase, 0.83 (95% CI: 0.77-0.90) versus pre-intervention phase, 0.73 (95% CI: 0.69-0.77, p = 0.03). The retention probability increased from 0.59 (0.49-0.68) to 0.73 (0.59-0.86), p = 0.03 among participants aged 18-24 years, and from 0.75 (0.71-0.78) to 0.85 (0.78-0.91), p = 0.03 among participants aged ≥ 25 years. VS (< 1,000 copies/mL) was approximately 87% in both phases., Conclusions: After implementation of the case management intervention, we observed significant improvement in 6-month retention in all age groups of a highly mobile population of predominantly fisher folk., (© 2022. The Author(s).)

Background: Despite being a priority population for COVID-19 vaccination, limited data are available regarding acceptability of COVID-19 vaccines among people living with HIV (PLWH) in Sub-Saharan Africa. We described COVID-19 vaccine acceptability and factors associated with vaccine acceptability among PLWH in Uganda., Methods: This was a cross-sectional study conducted among PLWH, aged ≥18 years, enrolled participants who were seeking HIV care from six purposely selected accredited ART clinics in Kampala. We obtained data on vaccine acceptability defined as willingness to accept any of the available COVID-19 vaccines using interviewer-administered questionnaires. In addition, we assessed vaccination status, complacency regarding COVID-19 disease, vaccine confidence, and vaccine convenience. Factors associated with COVID-19 vaccine acceptability were evaluated using modified Poisson regression with robust standard errors., Results: We enrolled 767 participants of whom 485 (63%) were women. The median age was 33 years [interquartile range (IQR) 28-40] for women and 40 years [IQR], (34-47) for men. Of the respondents 534 (69.6%,95% confidence interval [CI]: 66.3%-72.8%) reported receiving at least one vaccine dose, with women significantly more likely than men to have been vaccinated (73% vs. 63%; p = 0.003). Among the unvaccinated 169 (72.7%, 95% CI: 66.6%-78.0%) were willing to accept vaccination, had greater vaccine confidence (85.9% had strong belief that the vaccines were effective; 81.9% that they were beneficial and 71% safe for PLWH; 90.5% had trust in health care professionals or 77.4% top government officials), and believed that it would be easy to obtain a vaccine if one decided to be vaccinated (83.6%). Vaccine acceptability was positively associated with greater vaccine confidence (adjusted prevalence ratio [aPR] 1.44; 95% CI: 1.08-1.90), and positive perception that it would be easy to obtain a vaccine (aPR 1.57; 95% CI: 1.26-1.96)., Conclusion: vaccine acceptance was high among this cohort of PLWH, and was positively associated with greater vaccine confidence, and perceived easiness (convince) to obtained the vaccine. Building vaccine confidence and making vaccines easily accessible should be a priority for vaccination programs targeting PLWH., Competing Interests: The author(s) declare that they have no competing interests., (Copyright: © 2022 Muhindo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Uganda enforced several stringent restrictions such as night-time curfews, travel bans, school closure, and physical and social distancing among others that constituted a national lockdown to prevent the spread of the Coronavirus disease 2019 (COVID-19). These restrictions disrupted the delivery of health services but the impact on outcomes of human immunodeficiency virus (HIV) care has not been rigorously studied. We evaluated the effect of the COVID-19 pandemic restrictions on outcomes of HIV care among people living with HIV (PLHIV) aged ≥15 years in Kampala, Uganda. We designed a nonrandomized, quasi-experimental study using observational data retrieved from six large HIV clinics and used the data to construct two cohorts: a comparison cohort nonexposed to the restrictions and an exposed cohort that experienced the restrictions. The comparison cohort consisted of PLHIV commenced on anti-retroviral therapy (ART) between March 1, 2018, and February 28, 2019, followed for ≥1 year with outcomes assessed in March 2020, just before the restrictions were imposed. The exposed cohort comprised of PLHIV started on ART between March 1, 2019, and February 28, 2020, followed for ≥1 year with outcomes assessed in June 2021. The primary outcomes are retention, viral load testing, viral load suppression, and mortality. We employed inverse probability of treatment weighting using propensity score (IPTW-PS) to achieve comparability between the two cohorts on selected covariates. We estimated the effect of the restriction on the outcomes using logistic regression analysis weighted by propensity scores (PS), reported as odds ratio (OR) and 95% confidence interval (CI). We analyzed data for nine, 952 participants, with 5094 (51.2%) in the exposed group. The overall mean age was 32.7 ± 8.8 years. In the exposed group relative to the comparison group, viral load testing (OR, 1.68; 95% CI, 1.59-1.78) and viral load suppression (OR, 1.34; 95% CI, 1.110-1.63) increased while retention (OR, 0.76; 95% CI, 0.70-0.81) and mortality (OR, 0.75; 95% CI, 0.64-0.88) reduced. Among PLHIV in Kampala, Uganda, viral load testing and suppression improved while retention and mortality reduced during the COVID-19 pandemic restrictions due to new approaches to ART delivery and the scale-up of existing ART delivery models., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Observational studies provide important evidence supporting the feasibility and effectiveness of health interventions. The 20-year-old Infectious Diseases Institute (IDI) established to respond to infectious diseases, specifically HIV/AIDS, invested in the set-up of longitudinal cohorts. In this paper we discuss the results of these cohorts and their impact on the response to the HIV pandemic in Uganda., Methods: IDI invested in experienced system developers, clinic and laboratory capacity to create the infrastructure to host longitudinal cohorts. Several cohorts were created, including patients initiated and followed up on ART, specialized cohorts (e.g. TB co-infection) and long-term cohorts with patients on ART for over 10 years and aged 60 and above. These cohorts function as platforms for sub-studies, attracting collaborators and students., Results: Data from the IDI cohorts contributed evidence to ART programs on when to start, which drugs to use, how to best monitor and which models of care to implement. Sub-studies contributed to management of opportunistic infections, understanding immunological response and the emerging complications of non-communicable diseases., Conclusion: Cohorts provide a platform for clinical care, training, and research to inform strategic responses and put Makerere University at the center of the response to the HIV pandemic in the region., (© 2022 Castelnuovo B et al.)

Background: WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine., Methods: In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete., Findings: Between July 30 and Dec 18, 2019, we screened 783 patients and enrolled 465. One participant was randomly assigned in error and immediately withdrawn. The remaining 464 participants were randomly assigned to receive either dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either tenofovir (n=233) or zidovudine (n=231). At week 96, 211 (90%) of 235 participants in the dolutegravir group and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per mL (percentage point difference 2·9, 95% CI -3·0 to 8·7), indicating non-inferiority. Nine (4%) participants (all in the dolutegravir group) developed dolutegravir resistance; no participants developed darunavir resistance (p=0·0023). In the other randomised comparison, 214 (92%) of 233 patients in the tenofovir group and 196 (85%) of 231 patients in the zidovudine group had HIV-1 RNA less than 400 copies per mL (percentage point difference 7·0, 95% CI 1·2 to 12·8), showing non-inferiority and indicating the superiority of tenofovir (p=0·019). The proportions of participants with any grade 3-4 adverse event were similar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (22 [9%]) and zidovudine (32 [14%]) groups. There were no deaths related to study medication., Interpretation: Dolutegravir-based and darunavir-based regimens maintain good viral suppression during 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second-line therapy. Tenofovir should be continued in second-line therapy, rather than being switched to zidovudine., Funding: Janssen., Competing Interests: Declaration of interests NIP reports grants paid to his institution and personal fees from Janssen. CK, AL, and HM report grants and the donation of drugs and trial supplies to their institutions from Janssen. AKam reports grants paid to his institution from Janssen. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Prompt diagnosis and treatment of sexually transmitted infections (STIs) are essential to combat the STI epidemic in resource-limited settings. We characterized the burden of 5 curable STIs chlamydia, gonorrhea, trichomoniasis, Mycoplasma genitalium, syphilis, and HIV infection in Ugandan men with urethritis., Methods: Participants were recruited from a gonococcal surveillance program in Kampala, Uganda. Questionnaires, penile swabs were collected and tested by nucleic acid amplification. Gonococcal isolates were tested for antimicrobial sensitivity. Sequential point-of-care tests on blood samples were used to screen for syphilis and HIV. Bivariable and multivariable multinomial logistic regression models were used to estimate odds ratios for preselected factors likely to be associated with STIs. Adherence to STI treatment guidelines were analyzed., Results: From October 2019 to November 2020, positivity (95% CI) for gonorrhea, chlamydia, trichomoniasis, and Mycoplasma genitalium, were 66.4% (60.1%, 72.2%), 21.7% (16.8%, 27.4%), 2.0% (0.7%, 4.9%), and 12.4% (8.7%, 17.3%) respectively. All Neisseria gonorrhoeae isolates were resistant to ciprofloxacin, penicillin, and tetracycline, but susceptible to extended spectrum cephalosporins and azithromycin. HIV and syphilis prevalence was 20.0% (50/250) and 10.0% (25/250), and the proportion unaware of their infection was 4.0% and 80.0% respectively. Most participants were treated per national guidelines. Multivariable analysis demonstrated significant associations between curable STI coinfections and younger age, transactional sex, but not HIV status, nor condom or alcohol use., Conclusions: STI coinfections including HIV their associated risk factors, and gonococcal AMR were common in this population. The majority with syphilis were unaware of their infection and were untreated. Transactional sex was associated with STI coinfections, and > 80% of participants received appropriate treatment., (© 2022. The Author(s).)

Objectives: Efforts to achieve zero transmission of HIV to infants born to women living with HIV in sub-Saharan African are undermined by high rates of loss to follow-up in prevention of vertical transmission (PVT) programmes. The fear of HIV status disclosure through the discovery of pill bottles at home is a major contributor. Injectable antiretroviral therapy (ART) has proved to be efficacious in clinical trials and is discreet, offering a potential solution. We investigated the knowledge and willingness to use injectable ART among women who were lost to follow-up from the PVT programme in Uganda., Methods: Women were traced by nurse counsellors and knowledge and opinions relating to injectable ART, including willingness to use it when it becomes available, were collected. Generalized linear models were used to determine predictors of willingness to use injectable ART., Conclusions: Among 1023 women registered between 2017 and 2019 under the PVT programmes in Kampala and Wakiso districts, Uganda, 385 (38%) were lost to follow-up from care and 22% of these (83/385) were successfully traced and interviewed. Only 25% (21/83) had heard of injectable ART. Over half (55%, 46/83) were very willing to use injectable ART, 40% (33/83) were somewhat willing and four (5%) were not willing. Those who associated ART tablets with disclosure risk were more willing to consider injectable ART (adjusted odds ratio = 4.21; 95% confidence interval: 1.45-12.19; p = 0.008). We report high willingness to use injectable ART associated with fears that ART tablets were a potential source of HIV status disclosure. Injectable ART could be a solution for women who have challenges with disclosure., (© 2022 British HIV Association.)

We developed and pilot tested a 3-month HIV self-testing intervention called HiSTEP ("HIV Self-testing Engagement Project") among 95 adult (18+ years) at-risk (condomless sex < 3 months) adults in Kampala, Uganda. HiSTEP leverages theoretically-grounded (in the Information-Motivation-Behavioral Skills model) text messages, a telehealth centre with live support, and "last-mile" HIV self-testing kit delivery to a location chosen by the participant. Nearly 94% of participants were retained at month 3. HIV self-testing was highly acceptable across age and gender groups (94% very satisfied), although older women had slightly lower acceptability ratings (92% very satisfied). Only 13% of participants used HIV self-testing prior to enrollment. Over the 3-month study period, 86% of participants ordered a total of 169 HIV self-testing kits (69% for participant use; 31% for use by others). Findings show that the intervention approach taken in HiSTEP may be particularly valuable for engaging at-risk Ugandan adults in HIV self-testing using a novel technology-assisted promotion and delivery method., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Evidence shows benefit of digital technology for people living with human immunodeficiency virus on antiretroviral therapy adherence and retention in care, however, scalability and sustainability have scarcely been evaluated. We assessed participants' willingness to pay a fee for mHealth "Call for life Uganda" support, a mobile-phone based tool with the objective to assess sustainability and scalability., Methods: "Call for Life study", approved by Makerere University, School of Public Health research & ethics committee, at 2 sites in Uganda, evaluated a MoTech based software "CONNECT FOR LIFE™" mHealth tool termed "Call for life Uganda". It provides short messages service or Interactive Voice Response functionalities, with a web-based interface, allows a computer to interact with humans through use of voice and tones input via keypad. Participants were randomized at 1:1 ratio to Standard of Care or standard of care plus Call for life Uganda. This sends pill reminders, visit reminders, voice messages and self-reported symptom support. At study visits 18 and 24 months, through mixed method approach we assessed mHealth sustainability and scalability. Participants were interviewed on desire to have or continue adherence support and willingness to pay a nominal fee for tool. We computed proportions willing to pay (± 95% confidence interval), stratified by study arm and predictors of willingness to continue and to pay using multivariate logistic regression model backed up by themes from qualitative interviews., Results: 95% of participants were willing to continue using C4LU with 77.8% willing to pay for the service. Persons receiving care at the peri-urban clinic (OR 3.12, 95% CI 1.43-9.11.86) and those with exposure to the C4LU intervention (OR 4.2, 95% CI 1.55-11.84) were more likely to continue and pay for the service. Qualitative interviews revealed mixed feelings regarding amounts to pay, those willing to pay, argued that since they have been paying for personal phone calls/messages, they should not fail to pay for Call for life., Conclusions: Payment for the service offers opportunities to scale up and sustain mHealth interventions which may not be priorities for government funding. A co-pay model could be acceptable to PLHIV to access mHealth services in low resource settings. Clinical Trial Number NCT02953080., (© 2022. The Author(s).)

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., (© 2021. The Author(s).)

Background: Retention of pregnant and breastfeeding women and their infants in HIV care still remains low in Uganda. Recent literature has shown that the effects of COVID-19 mitigation measures may increase disease burden of common illnesses including HIV, Tuberculosis, Malaria and other key public health outcomes such as maternal mortality. A research program was undertaken to locate disengaged HIV positive women on option B+ and supported them to reengage in care. A 1 year follow up done following the tracing revealed that some women still disengaged from care. We aimed to establish the barriers to and facilitators for reengagement in care among previously traced women on option B+, and how these could have been impacted by the COVID-19 pandemic., Methods: This was a cross sectional qualitative study using individual interviews conducted in June and July, 2020, a period when the COVID-19 response measures such as lockdown and restrictions on transport were being observed in Uganda. Study participants were drawn from nine peri-urban and rural public healthcare facilities. Purposive sampling was used to select women still engaged in and those who disengaged from care approximately after 1 year since they were last contacted. Seventeen participants were included. Data was analysed using the content analysis approach., Results: Women reported various barriers that affected their reengagement and retention in care during the COVID-19 pandemic. These included structural barriers such as transport difficulties and financial constraints; clinical barriers which included unsupportive healthcare workers, short supply of drugs, clinic delays, lack of privacy and medicine side effects; and psychosocial barriers such as perceived or experienced stigma and non-disclosure of HIV sero-status. Supportive structures such as family, community-based medicine distribution models, and a friendly healthcare environment were key facilitators to retention in care among this group. The COVID-19 pandemic was reported to exacerbate the barriers to retention in care., Conclusions: COVID-19 may exacerbate barriers to retention in HIV care among those who have experienced previous disengagement. We recommend community-based models such as drop out centres, peer facilitated distribution and community outreaches as alternative measures for access to ART during the COVID-19 pandemic., (© 2021. The Author(s).)

In sub-Saharan Africa (SSA), men are generally difficult to engage in healthcare programs. However, sports gambling centers in SSA can be used as avenues for male engagement in health programs. We offered point-of-care HIV and syphilis testing for men located at five gambling centers in Uganda and assessed HIV risky sexual behavior. Among 507 men, 0.8% were HIV-positive and 3.8% had syphilis. Risky sexual behavior included condomless sex with partner(s) of unknown HIV status (64.9%), having multiple sexual partners (47.8%), engaging in transactional sex (15.5%), and using illicit drugs (9.3%). The majority at 64.5% were nonalcohol consumers, 22.9% were moderate users, and 12.6% had hazardous consumption patterns. In 12 months of follow-up, the incidence rate of syphilis was 0.95 (95% CI: 0.82-1.06) among 178 men. Thus, men in SSA have a high prevalence of syphilis and risky sexual behavior which should be more effectively addressed to reduce the risk of HIV acquisition.

Background: The World Health Organization recommends dolutegravir with two nucleoside reverse-transcriptase inhibitors (NRTIs) for second-line treatment of human immunodeficiency virus type 1 (HIV-1) infection. Evidence is limited for the efficacy of this regimen when NRTIs are predicted to lack activity because of drug resistance, as well as for the recommended switch of an NRTI from tenofovir to zidovudine., Methods: In a two-by-two factorial, open-label, noninferiority trial, we randomly assigned patients for whom first-line therapy was failing (HIV-1 viral load, ≥1000 copies per milliliter) to receive dolutegravir or ritonavir-boosted darunavir and to receive tenofovir or zidovudine; all patients received lamivudine. The primary outcome was a week 48 viral load of less than 400 copies per milliliter, assessed with the Food and Drug Administration snapshot algorithm (noninferiority margin for the between-group difference in the percentage of patients with the primary outcome, 12 percentage points)., Results: We enrolled 464 patients at seven sub-Saharan African sites. A week 48 viral load of less than 400 copies per milliliter was observed in 90.2% of the patients in the dolutegravir group (212 of 235) and in 91.7% of those in the darunavir group (210 of 229) (difference, -1.5 percentage points; 95% confidence interval [CI], -6.7 to 3.7; P = 0.58; indicating noninferiority of dolutegravir, without superiority) and in 92.3% of the patients in the tenofovir group (215 of 233) and in 89.6% of those in the zidovudine group (207 of 231) (difference, 2.7 percentage points; 95% CI, -2.6 to 7.9; P = 0.32; indicating noninferiority of tenofovir, without superiority). In the subgroup of patients with no NRTIs that were predicted to have activity, a viral load of less than 400 copies per milliliter was observed in more than 90% of the patients in the dolutegravir group and the darunavir group. The incidence of adverse events did not differ substantially between the groups in either factorial comparison., Conclusions: Dolutegravir in combination with NRTIs was effective in treating patients with HIV-1 infection, including those with extensive NRTI resistance in whom no NRTIs were predicted to have activity. Tenofovir was noninferior to zidovudine as second-line therapy. (Funded by Janssen; NADIA ClinicalTrials.gov number, NCT03988452.)., (Copyright © 2021 Massachusetts Medical Society.)

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., (©Adelline Twimukye, Agnes Bwanika Naggirinya, Rosalind Parkes-Ratanshi, Ronnie Kasirye, Agnes Kiragga, Barbara Castelnuovo, Jacob Wasswa, Maria Sarah Nabaggala, Elly Katabira, Mohammed Lamorde, Rachel Lisa King. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 14.06.2021.)

Introduction: Loss-to-follow-up among women living with HIV (WLWHIV) may lead to unfavorable outcomes for both mother and exposed infant. This study traced WLWHIV disengaged from care and their infants and compared their outcomes with those retained in care., Methods: The study included WLWHIV who initiated ART during pregnancy at six public clinics in Uganda. A woman was defined as disengaged (DW) if she had not attended her 6-week post-partum visit by 10 weeks after her estimated date of delivery. DW were matched with retained women (RW) by age and duration on ART. Nurse counselors traced all selected DW via telephone and community visits to assess vital status, infant HIV sero-status and maternal HIV viral load through blood draws., Results: Between July 2017 and July 2018, 734 women (359 DW and 375 RW) were identified for the study. Tracing was attempted on 349 DW and 160 (44.6%) were successfully located and enrolled in the study. They were matched with 162 RW. Among DW, 52 (32.5%) transferred to another health facility. Very few DW, 39.0% were HIV virally suppressed (<1000 copies/ml) compared to RW 89.5%, P<0.001). Among 138 babies born to DW, 4.3% tested positive for HIV compared to 1.4% among babies born to RW (P = 0.163)., Conclusion: Pregnant and breastfeeding WLWHIV who disengage from care are difficult to find in urban environments. Many have detectable viral loads, leading to the potential for an increased risk of MTCT. Efforts to reduce disengagement from care are critical for the successful elimination of MTCT in resource-limited settings., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study was to establish the prevalence of asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in key populations at increased risk of transmission of HIV. Additionally, we aimed to identify the associated risk factors for asymptomatic sexually transmitted infections (STIs) and evaluate the acceptability of self-collected samples. Asymptomatic people living with HIV (PLHIV) in the following categories were offered testing: discordant couples, young adults, pregnant patients and those attending the 'most-at-risk-population' clinic. Patients provided first-pass urine, self-collected vaginal swabs or both to test for NG and CT by polymerase chain reaction using BD ProbeTec™. Patients also completed an acceptability questionnaire, including the negative partner of an HIV-positive participant. Three hundred and sixty-three PLHIV had an STI screen. Asymptomatic STIs were only diagnosed in women (prevalence 5.7%), overall prevalence 3.9% ( n = 14). Factors independently associated with an STI in women were being under 25 years (OR 9.63 95% CI 1.56-59.5) and having more than one sexual partner (OR 8.06 95% CI 1.07-60.6). Four hundred and seven completed the acceptability questionnaire. More than 95% of patients found self-sampling easy and comfortable and 83.8% would believe the results. Women significantly preferred the option of self-sampling, 56.9% versus 29.3% of men ( p < 0.001). Acceptability of self-sampling was high. Young women with or at risk of HIV are an important target for STI testing regardless of symptoms. There is need for diagnostic tests that are inexpensive, rapid and accurate especially in resource-limited settings.

Background: With countries moving toward the World Health Organization's "Treat All" recommendation, there is a need to initiate more HIV-infected persons into antiretroviral therapy (ART). In resource-limited settings, task shifting is 1 approach that can address clinician shortages., Setting: Uganda., Methods: We conducted a randomized controlled trial to test if nurse-initiated and monitored ART (NIMART) is noninferior to clinician-initiated and monitored ART in HIV-infected adults in Uganda. Study participants were HIV-infected, ART-naive, and clinically stable adults. The primary outcome was a composite end point of any of the following: all-cause mortality, virological failure, toxicity, and loss to follow-up at 12 months post-ART initiation., Results: Over half of the study cohort (1,760) was women (54.9%). The mean age was 35.1 years (SD 9.51). Five hundred thirty-three (31.6%) participants experienced the composite end point. At 12 months post-ART initiation, nurse-initiated and monitored ART was noninferior to clinician-initiated and monitored ART. The intention-to-treat site-adjusted risk differences for the composite end point were -4.1 [97.5% confidence interval (CI): = -9.8 to 0.2] with complete case analysis and -3.4 (97.5% CI: = -9.1 to 2.5) with multiple imputation analysis. Per-protocol site-adjusted risk differences were -3.6 (97.5% CI: = -10.5 to 0.6) for complete case analysis and -3.1 (-8.8 to 2.8) for multiple imputation analysis. This difference was within hypothesized margins (6%) for noninferiority., Conclusions: Nurses were noninferior to clinicians for initiation and monitoring of ART. Task shifting to trained nurses is a viable means to increase access to ART. Future studies should evaluate NIMART for other groups (e.g., children, adolescents, and unstable patients)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: Following the successful scale-up of antiretroviral therapy (ART), the focus is now on ensuring good quality of life (QoL) and sustained viral suppression in people living with HIV. The access to mobile technology in the most burdened countries is increasing rapidly, and therefore, mobile health (mHealth) technologies could be leveraged to improve QoL in people living with HIV. However, data on the impact of mHealth tools on the QoL in people living with HIV are limited to the evaluation of SMS text messaging; these are infeasible in high-illiteracy settings., Objective: The primary and secondary outcomes were to determine the impact of interactive voice response (IVR) technology on Medical Outcomes Study HIV QoL scores and viral suppression at 12 months, respectively., Methods: Within the Call for Life study, ART-experienced and ART-naïve people living with HIV commencing ART were randomized (1:1 ratio) to the control (no IVR support) or intervention arm (daily adherence and pre-appointment reminders, health information tips, and option to report symptoms). The software evaluated was Call for Life Uganda, an IVR technology that is based on the Mobile Technology for Community Health open-source software. Eligibility criteria for participation included access to a phone, fluency in local languages, and provision of consent. The differences in differences (DIDs) were computed, adjusting for baseline HIV RNA and CD4., Results: Overall, 600 participants (413 female, 68.8%) were enrolled and followed-up for 12 months. In the intervention arm of 300 participants, 298 (99.3%) opted for IVR and 2 (0.7%) chose SMS text messaging as the mode of receiving reminders and health tips. At 12 months, there was no overall difference in the QoL between the intervention and control arms (DID=0.0; P=.99) or HIV RNA (DID=0.01; P=.94). At 12 months, 124 of the 256 (48.4%) active participants had picked up at least 50% of the calls. In the active intervention participants, high users (received >75% of reminders) had overall higher QoL compared to low users (received <25% of reminders) (92.2 versus 87.8, P=.02). Similarly, high users also had higher QoL scores in the mental health domain (93.1 versus 86.8, P=.008) and better appointment keeping. Similarly, participants with moderate use (51%-75%) had better viral suppression at 12 months (80/94, 85% versus 11/19, 58%, P=.006)., Conclusions: Overall, there was high uptake and acceptability of the IVR tool. While we found no overall difference in the QoL and viral suppression between study arms, people living with HIV with higher usage of the tool showed greater improvements in QoL, viral suppression, and appointment keeping. With the declining resources available to HIV programs and the increasing number of people living with HIV accessing ART, IVR technology could be used to support patient care. The tool may be helpful in situations where physical consultations are infeasible, including the current COVID epidemic., Trial Registration: ClinicalTrials.gov NCT02953080; https://clinicaltrials.gov/ct2/show/NCT02953080., (©Dathan Mirembe Byonanebye, Maria S Nabaggala, Agnes Bwanika Naggirinya, Mohammed Lamorde, Elizabeth Oseku, Rachel King, Noela Owarwo, Eva Laker, Richard Orama, Barbara Castelnuovo, Agnes Kiragga, Rosalind Parkes-Ratanshi. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 11.02.2021.)

Introduction: Cardiovascular disease (CVD) is the leading cause of death globally, representing 31% of all global deaths. HIV and long term anti-retroviral therapy (ART) are risk factors for development of CVD in populations of people living with HIV (PLHIV). CVD risk assessment tools are currently being applied to SSA populations, but there are questions about accuracy as well as implementation challenges of these tools in lower resource setting populations. We aimed to assess the level of agreement between the various cardiovascular screening tools (Data collection on Adverse effects of anti-HIV Drugs (D:A:D), Framingham risk score, WHO risk score and The Atherosclerotic Cardiovascular Disease Score) when applied to an HIV ART experienced population in Sub-Saharan Africa., Methods: This study was undertaken in an Anti-Retroviral Long Term (ALT) Cohort of 1000 PLHIV in care who have been on ART for at least 10 years in urban Uganda. A systematic review was undertaken to find the most frequently used screening tools from SSA PLHIV populations; these were applied to the ALT cohort. Levels of agreement between the resulting scores (those including lipids and non-lipids based, as well as HIV-specific and non-HIV specific) as applied to our cohort were compared. Prevalence Bias Adjusted Kappa was used to evaluate agreement between tools., Results: Overall, PLHIV in ALT cohort had a median score of 1.1-1.4% risk of a CVD event over 5 years and 1.7-2.5% risk of a CVD event over 10 years. There was no statistical difference in the risk scores obtained for this population when comparing the different tools, including comparisons of those with lipids and non-lipids, and HIV specific vs non-HIV specific., Conclusion: The various tools yielded similar results, but those not including lipids are more feasible to apply in our setting. Long-term cohorts of PLHIV in SSA should in future provide longitudinal data to evaluate existing CVD risk prediction tools for these populations. Inclusion of HIV and ART history factors to existing scoring systems may improve accuracy without adding the expense and technical difficulty of lipid testing., Competing Interests: The study was funded in part (SJR) by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health and Janssen pharmaceutical company through Johnson & Johnson corporate citizenship trust. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

We conducted a cross-sectional study to describe routine physical function assessment for HIV-infected adults aged ≥60 years attending a large urban HIV clinic in Kampala, Uganda. Assessed demographic and clinical factors associated with low physical function in the population, generalized linear regression model was used to estimate factors associated with low physical function. Of the 93 elderly patients that underwent the Short Physical Performance Battery (SPPB) assessment, 43/93 (44.1%) scored 1-8 points at the SPPB evaluation and were categorized as low function, 45/93 (48.4%) scored 9-11 points and were categorized as moderate function and 7/93 (7.5%) scored 12 points and were categorized as high (normal) function. Women (adjusted risk ratio (ARR) 2.57; 95% confidence interval (CI): 1.54-4.29, p  = 0.000) had increased risk of low physical function compared to men. A one-year increase in age (ARR = 1.09; CI: 1.03-1.15, p  = 0.004) and being overweight (BMI > 25.0, ARR = 1.96; CI: 1.89-3.24, p  = 0.008) also carried an increased risk of low physical function status. A higher number 13/41(32%) of falls was recorded in female than among male 3/53(5.8%) patients ( p  = 0.001). The SPPB assessment is a starting point for clinicians to comprehensively evaluate and consider the management of physical function limitation among older HIV-positive patients.

INTRODUCTION AND OBJECTIVE: In May 2018, the World Health Organization and other regulatory authorities released a safety alert for dolutegravir related to a risk of neural tube defects among women exposed to dolutegravir at the time of conception. Models of how drug safety information can be shared effectively in the shortest time are necessary to prevent interruptions of public health programs. We sought to describe an implementation process to inform and support women already on dolutegravir-based regimens at the time of conception to make informed choices following the safety alert of a potential teratogenicity risk. We describe the choices made by women, as well as determine the factors associated with women's choices to switch off dolutegravir., Methods: A clinic response plan was developed in the first week following the alert and clinic staff were trained on safety guidance. All women aged < 55 years taking dolutegravir were identified from the clinic database and contacted by phone for earlier appointments. Non-menopausal and non-surgically sterilized women were referred for urine pregnancy testing and evaluation of pregnancy intentions in the following 12 months and effective family planning was offered. We describe the coverage of women who received the communication as well as the fidelity to the outlined plan from 21 May to 12 September, 2018. We used modified a Poisson regression analysis to determine factors associated with switching off dolutegravir., Results: Of all active patients in the clinic, 9% (690/7963) were identified as female aged < 55 years taking dolutegravir. Ninety-five percent (656/690) were reviewed by September 2018 and informed of the safety alert, implying a high level of uptake. Fidelity to standard operating procedures was also high at 72%. Twenty-two percent (146/656) of patients were menopausal or surgically sterilized. Five hundred and ten women were of reproductive potential with a median age (interquartile range) of 37 years (30-42 years). Five percent (23/510) were human chorionic gonadotrophin positive and all initial ultrasound reports revealed no deformities. Twenty-one percent (108/510) had intentions to conceive and opted to stop taking dolutegravir with 90% (97/108) switching to efavirenz. Seventy-nine percent (402/510) opted to remain taking dolutegravir. However, only 40% (160/402) chose effective contraceptive methods and 60% (242/402) opted for condoms only/no contraceptive method., Conclusions: A rapid well-coordinated response ensured prompt communication of the dolutegravir safety warning. The process developed by the clinic can act as a model for response during drug safety alerts. Women made informed decisions with most opting to remain taking dolutegravir; however, effective contraception uptake was low.

Background: Despite advancement in Prevention of Mother to Child Transmission (PMTCT) services, the rate of MTCT of HIV in sub-Saharan Africa is still high. This is partly due to low retention of HIV positive mothers in HIV care. We sought to determine the level of retention and the factors associated with retention among HIV positive pregnant and breastfeeding mothers following accreditation of an antiretroviral therapy (ART) clinic to offer full time ART services in one of the lower health facilities in rural Western Uganda., Methods: This study was a mixed methods study conducted in 5 health centres in rural Western Uganda from 10th April to 10th May 2017. A total of 132 retained and non-retained HIV positive pregnant and breastfeeding mothers were recruited. A Mother was categorized as retained if she had not missed her ART appointments at antenatal or postnatal clinic for ≥3 consecutive months. Questionnaires were administered and four focus group discussions were held. We used descriptive statistics to understand characteristics of mothers and their levels of retention. Thematic analysis was used to analyze qualitative data., Results: About a third (35.6%) of the mothers were aged 18-24 with a median age of 26 (IQR 23, minimum age of 16 and maximum age of 39). More than half, 73 (55.3%) of all mothers were in HIV care for 3-24 months and about 116(87.9%) of all mothers were retained in HIV care. This was an improvement from 53% reported in 2015. We found lack of formal education, lack of disclosure of HIV status to the spouse, perceived lack of confidentiality and self stigmatization as factors hindering retention. The desire to have an HIV free baby, fear of death and opportunistic infections, support from significant others and community groups were factors associated with retention., Conclusions: We observed improved retention in lower health centres and to achieve 100% retention, we recommend interventions such as sensitizing HIV positive mothers on disclosure of HIV status to spouse, maintaining confidentiality of client information at the clinic, support to girl child education and formation of community support groups., Trial Registration: This study was retrospectively registered with the Uganda National Council for Science and Technology (UNCST), registration receipt number 10961 on the 9th March, 2018.

Background: The World Health Organisation approved boosted atazanavir as a preferred second line protease inhibitor in 2010. This is as an alternative to the current boosted lopinavir. Atazanavir has a lower genetic barrier than lopinavir. We compared the virological outcomes of patients during the roll out of routine viral load monitoring, who had switched to boosted second- line regimens of either atazanavir or lopinavir., Methods: This was a cross-sectional study involving adult patients at the Infectious Diseases Institute Kampala, Uganda started on a standard WHO recommended second-line regimen containing either boosted atazanavir or boosted lopinavir between 1 Dec 2014 and 31 July 2015.. Mantel -Haenszel chi square was used to test for the statistical significance of the odds of being suppressed (VL < 400 copies/ml) when on boosted atazanavir compared to boosted lopinavir after stratifying by duration on antiretroviral therapy (ART). Multivariate logistic regression analysis used to determine if the type of boosted protease inhibitor (bPI) was associated with virological outcome., Results: Ninety (90) % on ATV/r and 83% on LPV/r had a VL less than 1000 copies/ml. The odds of being suppressed using the same viral load cut-off while on boosted atazanavir compared to boosted lopinavir was not statistically significant after stratifying for duration on ART (p = 0.09). In a multivariate analysis the type of bPI used was not a predictor of virological outcome (p = 0.60)., Conclusions: Patients using the WHO recommended second-line of boosted atazanavir have comparable virological suppression to those on boosted lopinavir.

Background: HIV-infected persons with cryptococcal antigenemia (CrAg) are at high risk for meningitis or death. We evaluated the effect of CrAg screening and preemptive fluconazole therapy, adjunctive to antiretroviral therapy (ART), on 6-month survival among persons with advanced HIV/AIDS., Methods: We enrolled HIV-infected, ART-naive participants with <100 CD4 cells/µL, in a stepped-wedge, cluster-randomized trial from July 2012 to December 2014 at 17 Ugandan clinics. Clinics participated in a prospective observational phase, followed by an interventional phase with laboratory-based, reflexive CrAg screening of residual CD4 count plasma. Asymptomatic CrAg+ participants received preemptive fluconazole therapy. We assessed 6-month survival using Cox-regression, adjusting for nadir CD4, calendar time, and stepped-wedge steps., Results: We included 1280 observational and 2108 interventional participants, of whom 9.3% (195/2108) were CrAg+. CD4-, time-, and stepped-wedge-adjusted analyses demonstrated no difference in survival in the observational vs the interventional arms (hazard ratio = 1.34; 95% confidence interval: 0.86 to 2.10; P = 0.20). Fewer participants initiated ART in the interventional (73%) versus the observational phase (82%, P < 0.001). When ART initiation was modeled as a time-dependent covariate or confounder, survival did not differ. However, 6-month mortality of participants with CrAg titers <1:160 and CrAg-negative patients did not differ. Patients with CrAg titers ≥1:160 had 2.6-fold higher 6-month mortality than patients with titers <1:160., Conclusions: We observed no overall survival benefit of the CrAg screen-and-treat intervention. However, preemptive antifungal therapy for asymptomatic cryptococcosis seemed to be effective in patients with CrAg titer <1:160. A more aggressive approach is required for persons with CrAg titer ≥1:160.

Background: The roll out of antiretroviral therapy (ART) in Sub-Saharan Africa led to a decrease in mortality. Few studies have documented the causes of deaths among patients on long term antiretroviral therapy in Sub-Saharan Africa. Our objective was to describe the causes of death among patients on long term ART in Sub-Saharan Africa., Methods: We used data from a prospective cohort of ART naïve patients receiving care and treatment at the Infectious Diseases Institute in Kampala, Uganda. Patients were followed up for 10 years. All deaths were recorded and possible causes established using verbal autopsy. Deaths were grouped as HIV-related (ART toxicities, any opportunistic infections (OIs) and HIV-related malignancies) and non-HIV related deaths while some remained unknown. We used Kaplan Meier survival methods to estimate cumulative incidence and rates of mortality for all causes of death., Results: Of the 559, (386, 69%) were female, median age 36 years (IQR: 21-44), 89% had WHO clinical stages 3 and 4, and median CD4 count at ART initiation was 98 cells/μL (IQR: 21-163). A total of 127 (22.7%) deaths occurred in 10 years. The HIV related causes of death (n = 70) included the following; Tuberculosis 17 (24.3%), Cryptococcal meningitis 10 (15.7%), Kaposi's Sarcoma 7(10%), HIV related toxicity 6 (8.6%), HIV related anemia 5(7.1%), Pneumocystis carinii Pneumonia (PCP) 5 (7.1%), HIV related chronic diarrhea 4 (5.7%), Non-Hodgkin Lymphoma 3 (4.3%), Herpes Zoster 2 (2.8%), other 10 (14.3%). The non-HIV related causes of death (n = 20) included non-communicable diseases (diabetes, hypertension, stroke) 6 (30%), malaria 3 (15%), pregnancy-related death 2 (10%), cervical cancer 2 (10%), trauma 1(5%) and others 6 (30%)., Conclusion: Despite the higher rates of deaths from OIs in the early years of ART initiation, we observed an emergence of non-HIV related causes of morbidity and mortality. It is recommended that HIV programs in resource-limited settings start planning for screening and treatment of non-communicable diseases.

Background: Low retention on combination antiretroviral therapy (cART) has emerged as a threat to the Joint United Nations Programme on human immunodeficiency virus (HIV)/AIDS (UNAIDS) 90-90-90 targets. We examined outcomes of patients who started cART but were subsequently lost to follow-up (LTFU) in African treatment programs., Methods: This was a systematic review and individual patient data meta-analysis of studies that traced patients who were LTFU. Outcomes were analyzed using cumulative incidence functions and proportional hazards models for the competing risks of (i) death, (ii) alive but stopped cART, (iii) silent transfer to other clinics, and (iv) retention on cART., Results: Nine studies contributed data on 7377 patients who started cART and were subsequently LTFU in sub-Saharan Africa. The median CD4 count at the start of cART was 129 cells/μL. At 4 years after the last clinic visit, 21.8% (95% confidence interval [CI], 20.8%-22.7%) were known to have died, 22.6% (95% CI, 21.6%-23.6%) were alive but had stopped cART, 14.8% (95% CI, 14.0%-15.6%) had transferred to another clinic, 9.2% (95% CI, 8.5%-9.8%) were retained on cART, and 31.6% (95% CI, 30.6%-32.7%) could not been found. Mortality was associated with male sex, more advanced disease, and shorter cART duration; stopping cART with less advanced disease andlonger cART duration; and silent transfer with female sex and less advanced disease., Conclusions: Mortality in patients LTFU must be considered for unbiased assessments of program outcomes and UNAIDS targets in sub-Saharan Africa. Immediate start of cART and early tracing of patients LTFU should be priorities.

Objective: We conducted a retrospective cohort study to assess the effect of tracking People Living with HIV (PLHIV) after missed clinic visits and factors associated with return to care in rural Uganda. We assessed retention in care among 650 HIV-infected women and men. We used univariable and multivariable generalized linear models to assess demographic and self-reported factors associated with re-engagement in HIV care., Results: Of 381 PLHIV who ever missed a scheduled appointment, 68% were female and most (80%) had initiated ART. Most (70%) of those tracked returned to care. Relative to men, women (adjusted risk ratio [ARR] 1.23; 95% confidence interval (CI) 1.05-1.43; p = 0.009) were more likely to return to care after active tracking. PLHIV who missed scheduled visits for other reasons (forgetting, adequate drug supplies, or long distance to clinic) had reduced odds of return to care (ARR 0.41; 95% CI 0.28-0.59; p < 0.001). These data support close monitoring of patient retention in HIV care and active measures to re-engage those who miss an appointment. Furthermore, they highlight the need for targeted interventions to those more resistant to re-engagement such as men.

Background: Treatment with effective antiretroviral therapy (ART) lowers morbidity and mortality among HIV positive individuals. Effective highly active antiretroviral therapy (HAART) should lead to undetectable viral load within 6 months of initiation of therapy. Failure to achieve and maintain viral suppression may lead to development of resistance and increase the risk of viral transmission. In this paper three logistic regression based machine learning approaches are developed to predict early virological outcomes using easily measurable baseline demographic and clinical variables (age, body weight, sex, TB disease status, ART regimen, viral load, CD4 count). The predictive performance and generalizability of the approaches are compared., Methods: The multitask temporal logistic regression (MTLR), patient specific survival prediction (PSSP) and simple logistic regression (SLR) models were developed and validated using the IDI research cohort data and predictive performance tested on an external dataset from the EFV cohort. The model calibration and discrimination plots, discriminatory measures (AUROC, F1) and overall predictive performance (brier score) were assessed., Results: The MTLR model outperformed the PSSP and SLR models in terms of goodness of fit (RMSE = 0.053, 0.1, and 0.14 respectively), discrimination (AUROC = 0.92, 0.75 and 0.53 respectively) and general predictive performance (Brier score= 0.08, 0.19, 0.11 respectively). The predictive importance of variables varied with time after initiation of ART. The final MTLR model accurately (accuracy = 92.9%) predicted outcomes in the external (EFV cohort) dataset with satisfactory discrimination (0.878) and a low (6.9%) false positive rate., Conclusion: Multitask Logistic regression based models are capable of accurately predicting early virological suppression using readily available baseline demographic and clinical variables and could be used to derive a risk score for use in resource limited settings.

Introduction: Adolescence and pregnancy are potential risk factors for loss to follow-up (LTFU) while on antiretroviral therapy (ART). We compared adolescent and adult LTFU after ART initiation to quantify the impact of age, pregnancy, and site-level factors on LTFU., Methods: We used routine clinical data for patients initiating ART as young adolescents (YA; 10 to 14 years), older adolescents (OA; 15 to 19 years) and adults (≥20 years) from 2000 to 2014 at 52 health facilities affiliated with the International epidemiology Databases to Evaluate AIDS (IeDEA) East Africa collaboration. We estimated cumulative incidence (95% confidence interval, CI) of LTFU (no clinic visit for ≥6 months after ART initiation) and identified patient and site-level correlates of LTFU, using multivariable Cox proportional hazards models for all patients as well as individual age groups., Results: A total of 138,387 patients initiated ART, including 2496 YA, 2955 OA and 132,936 adults. Of these, 55%, 78% and 66%, respectively, were female and 0.7% of YA, 22.3% of OA and 8.3% of adults were pregnant at ART initiation. Cumulative incidence of LTFU at five years was 26.6% (24.6 to 28.6) among YA, 44.1% (41.8 to 46.3) among OA and 29.3% (29.1 to 29.6) among adults. Overall, compared to adults, the adjusted hazard ratio, aHR, (95% CI) of LTFU for OA was 1.54 (1.41 to 1.68) and 0.77 (0.69 to 0.86) for YA. Compared to males, pregnant females had higher hazard of LTFU, aHR 1.20 (1.14 to 1.27), and nonpregnant women had lower hazard aHR 0.90 (0.88 to 0.93). LTFU hazard among the OA was primarily driven by both pregnant and nonpregnant females, aHR 2.42 (1.98 to 2.95) and 1.51 (1.27 to 1.80), respectively, compared to men. The LTFU hazard ratio varied by IeDEA program. Site-level factors associated with overall lower LTFU hazard included receiving care in tertiary versus primary-care clinics aHR 0.61 (0.56 to 0.67), integrated adult and adolescent services and food ration provision aHR 0.93 (0.89 to 0.97) versus nonintegrated clinics with food ration provision, having patient support groups aHR 0.77 (0.66 to 0.90) and group adherence counselling aHR 0.61 (0.57 to 0.67)., Conclusions: Older adolescents experienced higher risk of LTFU compared to YA and adults. Interventions to prevent LTFU among older adolescents are critically needed, particularly for female and/or pregnant adolescents., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

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.

Objective: The aim of this study was to use a sampling-based approach to obtain estimates of retention in HIV care before initiation of antiretroviral treatment (ART), corrected for outcomes in patients who were lost according to clinic registers., Design: Retrospective cohort study of HIV-positive individuals not yet eligible for ART (CD4 >500)., Setting: Three urban and three rural HIV care clinics in Uganda; information was extracted from the clinic registers for all patients who had registered for pre-ART care between January and August 2015., Participants: A random sample of patients who were lost according to the clinic registers (>3 months late to scheduled visit) was traced to ascertain their outcomes., Outcome Measures: The proportion of patients lost from care was estimated using a competing risks approach, first based on the information in the clinic records alone and then using inverse probability weights to incorporate the results from tracing. Cox regression was used to determine factors associated with loss from care., Results: Of 1153 patients registered for pre-ART care (68% women, median age 29 years, median CD4 count 645 cells/µL), 307 (27%) were lost according to clinic records. Among these, 195 (63%) were selected for tracing; outcomes were ascertained in 118 (61%). Seven patients (6%) had died, 40 (34%) were in care elsewhere and 71 (60%) were out of care. Loss from care at 9 months was 30.2% (95% CI 27.3% to 33.5%). After incorporating outcomes from tracing, loss from care decreased to 18.5% (95% CI 13.8% to 23.6%)., Conclusion: Estimates of loss from HIV care may be too high if based on routine clinic data alone. A sampling-based approach is a feasible way of obtaining more accurate estimates of retention, accounting for transfers to other clinics., Competing Interests: Competing interests: PN and JB had research grant support from EDCTP for the submitted work; KB and JB receive research grants from MRC UK and DFID; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: Little information is available on patients on antiretroviral treatment (ART) after a long-term period from sub-Saharan Africa, with the longest follow-up and related outcomes being after 10 years on ART. At the Infectious Diseases Institute (IDI) (Kampala, Uganda), we set up a cohort of patients already on ART for 10 years at the time of enrolment, who will be followed up for additional 10 years., Participants: A prospective observational cohort of 1000 adult patients previously on ART for 10 years was enrolled between May 2014 and September 2015. Patients were eligible for enrolment if they were in their consecutive 10th year of ART regardless of the combination of drugs for both first- and second-line ART. Data were collected at enrolment and all annual study visits. Follow-up visits are scheduled once a year for 10 years. Biological samples (packed cells, plasma and serum) are stored at enrolment and follow-up visits., Findings to Date: Out of 1000 patients enrolled, 345 (34.5%) originate from a pre-existing research cohort at IDI, while 655 (65.5%) were enrolled from the routine clinic. Overall, 81% of the patients were on first line at the time of the enrolment in the ART long-term cohort, with the more frequent regimen being zidovudine plus lamivudine plus nevirapine (44% of the cohort), followed by zidovudine plus lamivudine plus efavirenz (22%) and tenofovir plus lamivudine or emtricitabine plus efavirenz (10%). At cohort enrolment, viral suppression was defined as HIV-RNA <400 copies/mL was 95.8%., Future Plans: Through collaboration with other institutions, we are planning several substudies, including the evaluation of the risk for cardiovascular diseases, the assessment of bone mineral density, screening for liver cirrhosis using fibroscan technology and investigation of drug-drug interactions between ART and common drugs used for non-communicable diseases., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: In 2013, Uganda updated its prevention of maternal-to-child transmission of HIV program to Option B+, which requires that all HIV-infected pregnant and breastfeeding women be started on lifelong antiretroviral therapy (ART) regardless of CD4 count. We describe retention in care and factors associated with loss to follow-up (LTFU) among women initiated on Option B+ as part of an evaluation of the effectiveness of the national program., Methods: We conducted a retrospective cohort analysis of data abstracted from records of 2,169 women enrolled on Option B+ between January and March 2013 from a representative sample of 145 health facilities in all 24 districts of the Central region of Uganda. We defined retention as "being alive and receiving ART at the last clinic visit". We used Kaplan-Meier analysis to estimate retention in care and compared differences between women retained in care and those LTFU using the chi-squared test for dichotomized or categorical variables., Results: The median follow-up time was 20.2 months (IQR 4.2-22.5). The proportion of women retained in HIV care at 6, 12 and 18 months post-ART initiation was 74.2%, 66.7% and 62.0%, respectively. Retention at 18 months varied significantly by level of health facility and ranged from 70.0% among those seen at hospitals to 56.6% among those seen at lower level health facilities. LTFU was higher among women aged less than 25 years, 59.3% compared to those aged 25 years and above, 40.7% (p = 0.02); among those attending care at lower level facilities, 44.0% compared to those attending care at hospitals, 34.1% (p = 0.01), and among those who were not tested for CD4 cell count at ART initiation, 69.4% compared to those who were tested, 30.9% (p = 0.002)., Conclusion: Retention of women who were initiated on Option B+ during the early phases of roll-out was only moderate, and could undermine the effectiveness of the program. Identifying reasons why women drop out and designing targeted interventions for improved retention should be a priority.

Lifelong ART is essential to reducing HIV mortality and ending the epidemic, however the interplay between socioeconomic position and long-term outcomes of HIV-infected persons receiving antiretroviral therapy (ART) in sub-Saharan Africa is unknown. Furthering the understanding of factors related to long-term ART outcomes in this important region will aid the successful scale-up of ART programs. We enrolled 559 HIV-infected Ugandan adults starting ART in 2004-2005 at the Infectious Diseases Institute in Kampala, Uganda and followed them for 10 years. We documented baseline employment status, regular household income, education level, housing description, physical ability, and CD4 count. Viral load was measured every six months. Proportional hazard regression tested for associations between baseline characteristics and 1) mortality, 2) virologic failure, and 3) mortality or virologic failure as a composite outcome. Over ten years 23% (n = 127) of participants died, 6% (n = 31) were lost-to-follow-up and 23% (107/472) experienced virologic treatment failure. In Kaplan-Meier analysis we observed an association between employment and mortality, with the highest cumulative probability of death occurring in unemployed individuals. In univariate analysis unemployment and disease severity were associated with mortality, but in multivariable analysis the only association with mortality was disease severity. We observed an association between higher household income and an increased incidence of both virologic failure and the combined outcome, and an association between self-employment and lower incidence of virologic failure and the combined outcome when compared to unemployment. Formal education level and housing status were unrelated to outcomes. It is feasible to achieve good ten-year survival, retention-in-care, and viral suppression in a socioeconomically diverse population in a resource-limited setting. Unemployment appears to be related to adverse 10-year ART outcomes. A low level of formal education does not appear to be a barrier to successful long-term ART.

A wealth of genetic, demographic, clinical and biomarker data is collected from routine clinical care of HIV patients and exists in the form of medical records available among the medical care and research communities. Machine learning (ML) methods have the ability to identify and discover patterns in complex datasets and predict future outcomes of HIV treatment. We survey published studies that make use of ML techniques in HIV clinical research and care. An advanced search relevant to the use of ML in HIV research was conducted in the PubMed biomedical database. The survey outcomes of interest include data sources, ML techniques, ML tasks and ML application paradigms. A growing trend in application of ML in HIV research was observed. The application paradigm has diversified to include practical clinical application, but statistical analysis remains the most dominant application. There is an increase in the use of genomic sources of data and high performance non-parametric ML methods with a focus on combating resistance to antiretroviral therapy (ART). There is need for improvement in collection of health records data and increased training in ML so as to translate ML research into clinical application in HIV management., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: HIV-infected persons with detectable cryptococcal antigen (CrAg) in blood have increased morbidity and mortality compared with HIV-infected persons who are CrAg-negative. This study examined neurocognitive function among persons with asymptomatic cryptococcal antigenemia., Methods: Participants from three prospective HIV cohorts underwent neurocognitive testing at the time of antiretroviral therapy (ART) initiation. Cohorts included persons with cryptococcal meningitis (N = 90), asymptomatic CrAg + (N = 87), and HIV-infected persons without central nervous system infection (N = 125). Z-scores for each neurocognitive test were calculated relative to an HIV-negative Ugandan population with a composite quantitative neurocognitive performance Z-score (QNPZ-8) created from eight tested domains. Neurocognitive function was measured pre-ART for all three cohorts and additionally after 4 weeks of ART (and 6 weeks of pre-emptive fluconazole) treatment among asymptomatic CrAg + participants., Results: Cryptococcal meningitis and asymptomatic CrAg + participants had lower median CD4 counts (17 and 26 cells/μL, respectively) than the HIV-infected control cohort (233 cells/μL) as well as lower Karnofsky performance status (60 and 70 vs. 90, respectively). The composite QNPZ-8 for asymptomatic CrAg + (-1.80 Z-score) fell between the cryptococcal meningitis cohort (-2.22 Z-score, P = 0.02) and HIV-infected controls (-1.36, P = 0.003). After four weeks of ART and six weeks of fluconazole, the asymptomatic CrAg + cohort neurocognitive performance improved (-1.0 Z-score, P < 0.001)., Conclusion: Significant deficits in neurocognitive function were identified in asymptomatic CrAg + persons with advanced HIV/AIDS even without signs or sequelae of meningitis. Neurocognitive function in this group improves over time after initiation of pre-emptive fluconazole treatment and ART, but short term adherence support may be necessary.

In resource-limited settings, a number of patients do not receive continuous HIV care. In this analysis, we compared outcomes in patients who entered care by different modality of entry. This was a retrospective analysis of all patients started on antiretroviral treatment (ART) at a large urban center in Uganda from 2005 to 2012. Patients were categorized into three groups (1) Front door: started on ART without interruption during follow-up; (2) drop-out side door: restarted on ART after having an interruption >6 months and (3) transfer-in side door: transferred-in after being started on ART somewhere else. We compared characteristics at enrollment in the three groups and investigated the following outcomes: (1) retention in care (2) switch to second line. In the study period 11,528 (87.2%) were enrolled through the front door, 1159 (8.7%) resumed ART after dropping out, while 527 (4%) patients were transferred in on ART. The three groups were generally comparable, although patients transferred in were sicker. A larger proportion of patients entered through the drop-out side door died or was lost to follow-up (37.3%), as compared to patients in the front door group (24.9%) and transferred-in side door group (17.7%). More patients in the front door group (32.1%) were transferred out during the follow-up. The highest probability of switching to second line was found in the transferred-in group. Patients who re-enter our program after dropping out are at higher risk of dropping out of care and often need to be switched to second-line ART. The high demand for second-line therapy among patients in transfer-in side door reflects failure in management of complicated patients who are usually require "up-transfer" to better treatment centers. In future understanding, the different modes of entry into HIV care will be key in reshaping the general cascade of HIV care.

Objective: To describe patterns of suboptimal immune recovery (SO-IR) and associated HIV-related-illnesses during the first 5 years following first-line antiretroviral therapy (ART) initiation across seven ART sites in East Africa., Design: Retrospective analysis of data from seven ART clinical sites (three Uganda, two Kenya and two Tanzania)., Methods: SO-IR was described by proportions of ART-treated adults with CD4 cell counts less than 200, less than 350 and less than 500 cells/μl. Kaplan-Meier survival analysis techniques were used to assess predictors of SO-IR, and incident rates of HIV-related illnesses at CD4 cell counts less than 200, 200-350, 351-499, and >500 cells/μl, respectively., Results: Overall 80 843 adults initiated non-nucleoside reverse transcriptase inhibitor-based first-line ART; 65% were women and median CD4 cell count was 126 [interquartile range (IQR), 52-202] cells/μl. Cumulative probability of SO-IR <200 cells/μl, <350 cells/μl and <500 cells/μl, after 5 years, was 11, 38 and 63%, respectively. Incidence of HIV-related illnesses was higher among those with CD4 cell counts less than 200 and 200-350 cells/μl, than those who achieved CD4 counts above these thresholds. The most common events, at CD4 < 200 cells/μl, were pulmonary tuberculosis [incident rate 15.98 (15.47-16.51)/100 person-years at risk (PYAR), oral candidiasis [incident rate 12.5 (12.03-12.94)] and herpes zoster [incident rate 6.30 (5.99-6.64)] events/100 PYAR. With attainment of a CD4 cell count level 200-350 cells/μl, there was a substantial reduction in events/100 PYAR - by 91% to 1.45 (1.29-1.63) for TB, by 94% to 0.75 (0.64-0.89) for oral candidiasis, by 84% to 0.99 (0.86-1.14) for Herpes Zoster, and by 78% to 1.22 (1.07-1.39) for chronic diarrhea. The incidence of all events decreased further with CD4 counts above these thresholds., Conclusion: Around 40% of adults initiated on ART have suboptimal immune recovery with CD4 counts <350 cells/μl after five years. Such patients will require closer monitoring for both HIV-related and non-HIV-related clinical events.

Recent studies have evaluated cumulative human immunodeficiency virus type 1 (HIV-1) viral load (cVL) for predicting disease outcomes, with discrepant results. We reviewed the disparate methodological approaches taken and evaluated the prognostic utility of cVL in a resource-limited setting. Using data on the Infectious Diseases Institute (Makerere University, Kampala, Uganda) cohort, who initiated antiretroviral therapy in 2004-2005 and were followed up for 9 years, we calculated patients' time-updated cVL by summing the area under their viral load curves on either a linear scale (cVL1) or a logarithmic scale (cVL2). Using Cox proportional hazards models, we evaluated both metrics as predictors of incident opportunistic infections and mortality. Among 489 patients analyzed, neither cVL measure was a statistically significant predictor of opportunistic infection risk. In contrast, cVL2 (but not cVL1) was a statistically significant predictor of mortality, with each log10 increase corresponding to a 1.63-fold (95% confidence interval: 1.02, 2.60) elevation in mortality risk when cVL2 was accumulated from baseline. However, whether cVL is predictive or not hinges on difficult choices surrounding the cVL metric and statistical model employed. Previous studies may have suffered from confounding bias due to their focus on cVL1, which strongly correlates with other variables. Further methodological development is needed to illuminate whether the inconsistent predictive utility of cVL arises from causal relationships or from statistical artifacts., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The majority of studies from resource-limited settings only report short-term virological outcomes of patients on antiretroviral treatment (ART). We aim to describe the long-term durability of first-line ART and identify factors associated with long-term virological outcomes., Methods: At the Infectious Diseases Institute in Kampala, Uganda, 559 adult patients starting ART in 2004 were enrolled into a research cohort and monitored with viral load (VL) testing every six months for 10 years. We report the proportion and cumulative probability of 1) achieving virologic suppression (at least one VL <400 copies/ml); 2) experiencing virologic failure in patients who achieved suppression (two consecutive VLs >1000 copies/ml or one VL >5000, for those without a subsequent one); 3) treatment failure (not attaining virologic suppression or experiencing virologic failure). We used Cox regression methods to determine the characteristics associated with treatment failure. We included gender, baseline age, WHO stage, body mass index, CD4 count, propensity score for initial ART regimen, VL, time-dependent CD4 count and adherence., Results: Of the 559 patients enrolled, 472 (84.8%) had at least one VL (67 died, 13 were lost to follow-up, 4 transferred, 2 had no VL available); 73.6% started on d4T/3TC/nevirapine and 26.4% on AZT/3TC/efavirenz. Patients in the two groups had similar characteristics, except for the higher proportion of patients in WHO Stage 3/4 and higher VL in the efavirenz-based group. Four hundred thirty-nine (93%) patients achieved virologic suppression with a cumulative probability of 0.94 (confidence interval (CI): 0.92-0.96); 74/439 (16.9%) experienced virologic failure with a cumulative probability of 0.18 (CI: 0.15-0.22). In the multivariate analysis, initial d4T/3TC/nevirapine regimen (hazard ratio (HR): 3.02; CI: 3.02 (1.66-5.44, p<0.001)) and baseline VL ≥5 log10 copies/ml (HR: 2.29; CI: 1.29-4.04) were associated with treatment failures; patients of older age (HR: 0.87 per five-year increase; CI: 0.77-0.99), with adherence >95% (HR: 0.04; CI: 0.02-0.11) and with higher time-dependent CD4 count (HR: 0.94 per 50 cells/µl increase; CI: 0.92-0.99, p<0.001) were less likely to experience treatment failure., Conclusions: The long-term virological outcomes from this cohort are promising and comparable to those from research-rich settings. Our results provide further evidence that efavirenz is associated with better virological outcomes.

Introduction: Improving HIV outcomes among severely immunocompromised HIV-infected persons who have increased morbidity and mortality remains an important issue in sub-Saharan Africa. We sought to evaluate the impact of targeted clinic-based nurse care on antiretroviral therapy (ART) initiation and retention among severely immunocompromised HIV-infected persons., Methods: The study included ART-naive patients with CD4 counts <100 cells per microliter registered in seven urban clinics in Kampala, Uganda. Data were retrospectively collected on patients enrolled from July to December 2011 (routine care cohort). Between July 2012 and September 2013, 1 additional nurse per clinic was hired (nurse counselor cohort) to identify new patients, expedite ART initiation, and trace those who were lost to follow-up. We compared time to ART initiation and 6-month retention in care between cohorts and used a generalized linear model to estimate the relative risk of retention., Results: The study included 258 patients in the routine care cohort and 593 in the nurse counselor cohort. The proportion of patients who initiated ART increased from 190 (73.6%) in the routine care cohort to 506 (85.3%) in the nurse counselor cohort (P < 0.001). At 6 months, 62% of the routine care cohort were retained in care versus 76% in the nurse counselor cohort (P = 0.001). A 21% increase in the likelihood of retention in the nurse counselor cohort (relative risk: 1.21, 95% CI: 1.09 to 1.34) compared with the routine care cohort was observed., Conclusions: Implementation of targeted nurse-led care of severely immunocompromised HIV-infected patients in public outpatient health care facilities resulted in decreased time to ART initiation and increased retention.

Background: Short-medium term studies from sub-Saharan Africa show that, despite high early mortality, substantial loss to program, and high rates toxicity, patients on antiretroviral treatment have achieved outcomes comparable to those in developed settings. However, these studies were unable to account for long term outcomes of patients as they stayed longer on treatment., Objectives: We aim to describe ten years outcomes of one of the first cohort of HIV positive patients started on antiretroviral treatment (ART) in Sub-Saharan Africa., Methods: We report 10-years outcomes including mortality, retention, CD4-count response, virological outcomes, ART regimens change from a prospective cohort of 559 patients initiating ART and followed up for 10 years Uganda., Results: Of 559 patients, 69.1% were female, median age (IQR) was 38 (33-44) years, median CD4-count (IQR) 98 (21-163) cell/μL; 74% were started on stavudine, lamivudine and nevirapine, 26% on zidovudine, lamivudine and efavirenz. After 10 years 361 (65%) patients were still in the study; 127 (22.7%) had died; 30 (5%) were lost to follow-up; 27 (5%) transferred; 18 (3%) withdrew consent. The probability of death was high in the first year (0.15, 95%, CI 0.12-0.18). The median CD4 count increased from 98 to 589 cell/μL (IQR: 450-739 cell/μL) with a median increase of 357 cells/μL (IQR: 128-600 cells/μL); 7.4% never attained initial viral suppression and of those who did 31.7% experienced viral failure. Three hundred and two patients had at least one drug substitution while on first line after a median of 40 months; 66 (11.9%) of the patients were switched to a second line PI-based regimen due to confirmed treatment failure., Conclusions: Despite the high rate of early mortality due to advanced disease at presentation the outcomes from this cohort are encouraging, particularly the remarkable and incremental immune-recovery and a satisfactory rate of virologic suppression.