Antiretroviral Therapy In Uganda Research Articles

Evaluation of the effects of Artemisia Annua L. and Moringa Oleifera Lam. on CD4 count and viral load among PLWH on ART at Mbarara Regional Referral Hospital: a double-blind randomized controlled clinical trial

BackgroundInitiation of ART among people living with HIV (PLWH) having a CD4 count ≤ 350cells/µl, produces poor immunological recovery, putting them at a high risk of opportunistic infections. To mitigate this, PLWH on ART in Uganda frequently use herbal remedies like Artemisia annua and Moringa oleifera, but their clinical benefits and potential antiretroviral (ARV) interactions remain unknown. This study examined the impact of A. annua and M. oleifera on CD4 count, viral load, and potential ARV interactions among PLWH on ART at an HIV clinic in Uganda.Methods282 HIV-positive participants on antiretroviral therapy (ART) with a CD4 count ≤ 350cells/µl were randomized in a double-blind clinical trial to receive daily, in addition to their routine standard of care either; 1) A. annua leaf powder, 2) A. annua plus M. oleifera, and 3) routine standard of care only. Change in the CD4 count at 12 months was our primary outcome. Secondary outcomes included changes in viral load, complete blood count, and ARV plasma levels. Participants were followed up for a year and outcomes were measured at baseline, 6 and 12 months.ResultsAt 12 months of patient follow-up, in addition to standard of care, administration of A. annua + M. oleifera resulted in an absolute mean CD4 increment of 105.06 cells/µl, (p < 0.001), while administration of A. annua plus routine standard of care registered an absolute mean CD4 increment of 60.84 cells/µl, (p = 0.001) compared to the control group. The A. annua plus M. oleifera treatment significantly reduced viral load (p = 0.022) and increased platelet count (p = 0.025) and white blood cell counts (p = 0.003) compared to standard care alone, with no significant difference in ARV plasma levels across the groups.ConclusionA combination of A. annua and M. oleifera leaf powders taken once a day together with the routine standard of care produced a significant increase in CD4 count, WBCs, platelets, and viral load suppression among individuals on ART. A. annua and M. oleifera have potential to offer an affordable alternative remedy for managing HIV infection, particularly in low-resource communities lacking ART access.Trial registrationClinicalTrials.gov NCT03366922.

Association between smoking and lack of HIV virological suppression in a cross-sectional study of persons with HIV on antiretroviral therapy in Uganda.

Smoking and alcohol use frequently co-occur and are the leading causes of preventable death in sub-Saharan Africa (SSA) and are common among people living with HIV (PLWH). While alcohol use has been shown to be associated with reduced adherence to antiretroviral treatment (ART), which may affect HIV viral suppression, the independent effect of smoking on HIV outcomes in SSA is unknown. We aimed to 1) describe the prevalence of current smoking and correlates of smoking; 2) assess the association of smoking with viral suppression, adjusting for level of alcohol use; 3) explore the relationship between smoking and CD4 cell count <350 cells/mm3, among participants who are virally suppressed. We analyzed data from the Drinkers Intervention to Prevent Tuberculosis (DIPT) and the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) studies conducted in Southwest Uganda. The studies enrolled PLWH who were on ART for at least 6 months and co-infected with latent tuberculosis and dominated with participants who had unhealthy alcohol use. Current smoking (prior 3 months) was assessed by self-report. Alcohol use was assessed using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C, modified for prior 3 months) and phosphatidylethanol (PEth), an alcohol biomarker. We used logistic regression to estimate the cross-sectional association between smoking and lack of virological suppression (≥40 copies/ml), adjusting for level of alcohol use and other covariates, and to examine the association between smoking and CD4 cell counts among PLWH with viral suppression. Of the 955 participants enrolled from 2017 to 2021 who had viral load (VL) results, 63% were men, median age was 40 years (interquartile range [IQR] 32-47), 63% engaged in high/very high-risk alcohol use (AUDIT-C≥6 or PEth≥200 ng/mL), and 22% reported smoking in the prior 3 months. Among 865 participants (91%) with viral suppression and available CD4 count, 11% had a CD4 cell count <350 cells/mm3. In unadjusted and adjusted analyses, there was no evidence of an association between smoking and lack of virological suppression nor between smoking and CD4 count among those with viral suppression. The prevalence of smoking was high among a study sample of PLWH in HIV care with latent TB in Southwest Uganda in which the majority of persons engaged in alcohol use. Although there was no evidence of an association between smoking and lack of virological suppression, the co-occurrence of smoking among PLWH who use alcohol underscores the need for targeted and integrated approaches to reduce their co-existence and improve health.

Bone mineral density among children living with HIV failing first-line anti-retroviral therapy in Uganda: A sub-study of the CHAPAS-4 trial.

Children living with perinatally acquired HIV (CLWH) survive into adulthood on antiretroviral therapy (ART). HIV, ART, and malnutrition can all lead to low bone mineral density (BMD). Few studies have described bone health among CLWH in Sub-Saharan Africa. We determined the prevalence and factors associated with low BMD among CLWH switching to second-line ART in the CHAPAS-4 trial (ISRCTN22964075) in Uganda. BMD was determined using dual-energy X-ray Absorptiometry (DXA). BMD Z-scores were adjusted for age, sex, height and race. Demographic characteristics were summarized using median interquartile range (IQR) for continuous variables and proportions for categorical variables. Logistic regression was used to determine the associations between each variable and low BMD. A total of 159 children were enrolled (50% male) with median age (IQR) 10 (7-12) years, median duration of first -line ART 5.2(3.3-6.8) years; CD4 count 774 (528-1083) cells/mm3, weight-for-age Z-score -1.36 (-2.19, -0.65) and body mass index Z-score (BMIZ) -1.31 (-2.06, -0.6). Low (Z-score≤ -2) total body less head (TBLH) BMD was observed in 28 (18%) children, 21(13%) had low lumbar spine (LS) BMD, and15 (9%) had both. Low TBLH BMD was associated with increasing age (adjusted odds ratio [aOR] 1.37; 95% CI: 1.13-1.65, p = 0.001), female sex (aOR: 3.8; 95% CL: 1.31-10.81, p = 0.014), low BMI (aOR 0.36:95% CI: 0.21-0.61, p<0.001), and first-line zidovudine exposure (aOR: 3.68; 95% CI: 1.25-10.8, p = 0.018). CD4 count, viral load and first- line ART duration were not associated with TBLH BMD. Low LS BMD was associated with increasing age (aOR 1.42; 95% CI: 1.16-1.74, p = 0.001) and female sex: (aOR 3.41; 95% CI: 1.18-9.8, p = 0.023). Nearly 20% CLWH failing first-line ART had low BMD which was associated with female sex, older age, first-line ZDV exposure, and low BMI. Prevention, monitoring, and implications following transition to adult care should be prioritized to identify poor bone health in HIV+adolescents entering adulthood.

Effect of the "universal test and treat" policy on the characteristics of persons registering for HIV care and initiating antiretroviral therapy in Uganda.

We examined the effect of the Universal Test and Treat (UTT) policy on the characteristics of people living with HIV (PLHIV) at enrolment in HIV care and initiation of antiretroviral therapy (ART) in Uganda using data from 11 nationally representative clinics of The AIDS Support Organisation (TASO). We created two retrospective PLHIV cohorts: pre-UTT (2004-2016), where ART initiation was conditional on CD4 cell count and UTT (2017-2022), where ART was initiated regardless of World Health Organisation (WHO) clinical stage or CD4 cell count. We used a two-sample test of proportions and Wilcoxon rank-sum test to compare proportions and medians, respectively, between the cohorts. A total of 244,693 PLHIV were enrolled at the clinics [pre-UTT, 210,251 (85.9%); UTT, 34,442 (14.1%)]. Compared to the pre-UTT cohort, the UTT cohort had higher proportions of PLHIV that were male (p < 0.001), aged 18-29 years (p < 0.001), aged >69 years, never married (p < 0.001), and educated to primary (p < 0.001) and post-primary (p < 0.001) school level at enrolment in HIV care and ART initiation. Overall, 97.9% of UTT PLHIV initiated ART compared to 45.2% under pre-UTT. The median time from enrolment in HIV care to ART initiation decreased from 301 [interquartile range (IQR): 58-878] pre-UTT to 0 (IQR: 0-0) under UTT. The median CD4 count at ART initiation increased from 254 cells/μL pre-UTT to 482 cells/μL under UTT (p < 0.001). Compared to the pre-UTT cohort, the UTT cohort had higher proportions of PLHIV with a CD4 count >500 cells/μL (47.3% vs. 13.2%, p < 0.001) and WHO stage 1 (31.7% vs. 4.5%, p < 0.001) at ART initiation. Adoption of the UTT policy in Uganda was successful in enrolling previously unreached individuals, such as men and younger and older adults, as well as those with less advanced HIV disease. Future research will investigate the effect of UTT on long-term outcomes such as retention in care, HIV viral suppression, morbidity, and mortality.

Hopes, joys and fears: Meaning and perceptions of viral load testing and low-level viraemia among people on antiretroviral therapy in Uganda: A qualitative study.

Uganda applies the World Health Organization threshold of 1,000 copies/ml to determine HIV viral non-suppression. While there is an emerging concern of low-level viraemia (≥50 to <1,000 copies/ml), there is limited understanding of how people on antiretroviral therapy perceive viral load testing and low-level viremia in resource-limited settings. This qualitative study used the health belief model to explore the meaning that people living with HIV attach to viral load testing and low-level viraemia in Uganda. We used stratified purposive sampling to select people on antiretroviral therapy from eight high volume health facilities from the Central, Eastern, Northern and Western regions of Uganda. We used an interview guide, based on the health belief model, to conduct 32 in-depth interviews, which were audio-recorded and transcribed verbatim. Thematic analysis technique was used to analyze the data with the help of ATLAS.ti 6. The descriptions of viral load testing used by the participants nearly matched the medical meaning, and many people living with HIV understood what viral load testing was. Perceived benefits for viral load testing were the ability to show; the amount of HIV in the body, how the people living with HIV take their drugs, whether the drugs are working, and also guide the next treatments steps for the patients. Participants reported HIV stigma, lack of transport, lack of awareness for viral load testing, delayed and missing viral load results and few health workers as the main barriers to viral load testing. On the contrary, most participants did not know what low-level viraemia meant, while several perceived it as having a reduced viral load that is suppressed. Many people living with HIV are unaware about low-level viraemia, and hence do not understand its associated risks. Likewise, some people living with HIV are still not aware about viral load testing. Lack of transport, HIV stigma and delayed viral load results are major barriers to viral load testing. Hence, there is an imminent need to institute more strategies to create awareness about both low-level viraemia and viral load testing, manage HIV related stigma, and improve turnaround time for viral load results.

Serum E-selectin and endothelial cell-specific Molecule-1 levels among people living with HIV on long term ART in Uganda: a pilot cross-sectional study

BackgroundProlonged exposure to HIV and anti-retroviral therapy (ART) has been linked with endothelial cell activation which subsequently predisposes people living with HIV (PLWH) to cardiovascular diseases. Serum biomarkers of endothelial cell activation such as E-Selectin and endothelial cell-specific molecule-1 (ESM-1) could aid in early detection of PLWH at a risk of cardiovascular diseases. However, there is a paucity of data on these biomarkers like E-selectin and endothelial cell-specific molecule-1 (ESM-1) among PLWH on long term ART (≥ 10 years) in Uganda. The aim of this study is to determine the serum levels of these biomarkers in this population.MethodsThis was a cross-sectional study where we randomly sampled 73 stored serum samples of PLWH who were enrolled in the Infectious Diseases Institute (IDI) ART long term (ALT cohort). We measured serum levels of E-selectin and ESM-1 by ELISA. Data was summarized using median and interquartile range. Inferential statistics were performed to determine predictors of elevated levels of E-selectin.ResultsOf the 73 samples analyzed, 38 (52.1%) were from female participants. The mean age was 54 ± 9.0 years. Twenty participants (27.4%) had a history of smoking while 52 (71.2%) had a history of alcohol intake. Twenty-five (34.3%) of the participants were overweight whereas 4 (5.6%) were obese. Fifty-four (74%) had an undetectable viral load (≤ 0 copies/ml) and the mean duration of ART at the time of sampling (2014/2015) was 10.4 ± 0.4 years. While serum levels of ESM-1 were not detectable in any of our samples, the median E-selectin levels was 147.6 μm/L ranging from 8.44 μm/L and 1,979.36 μm/L. Sixty-seven participants (91.8%) had elevated levels of E-selectin (> 39 μm/L). CD4 count > 500 cells/µl compared to lower counts was a predictor of elevated levels of E-Selectin (adjusted Odd Ratio 12.5, 95% CI (1.03 — 149.95, p < 0.05).ConclusionsThe majority (91.8%) of PLWH on long term ART had elevated levels of E-selectin. Having high CD4 count (> 500 cells/µl) was predictive of elevated levels of E-Selectin. Future work should longitudinally assess the trend of levels of E-selectin and ESM-1 while assessing for cardiovascular diseases endpoint.

Prevalence of and Factors Associated with Hypertension Among Adults on Dolutegravir-Based Antiretroviral Therapy in Uganda: A Cross Sectional Study.

Dolutegravir-based anti-retroviral therapy (ART) regimens were rolled out as first line HIV treatment in Uganda due to their tolerability, efficacy and high resistance barrier to human immunodeficiency virus (HIV). They have however been associated with weight gain, dyslipidemia and hyperglycemia which are cardiometabolic risk factors of hypertension. We assessed the prevalence and factors associated with hypertension among adults on dolutegravir regimens. We conducted a cross-sectional study on 430 systematically sampled adults on dolutegravir-based ART for ≥ 6 months. Hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or history of use of antihypertensive agents. The prevalence of hypertension was 27.2% (117 of 430 participants) [95% CI: 23.2-31.6]. Majority were female (70.7%), the median age 42 [34, 50] years, with body mass index (BMI) ≥ 25 kg/m3 (59.6%) and median duration on DTG-based regimens of 28 [15, 33] months. Being male [aPR: 1.496, 95% CI: 1.122-1.994, P = 0.006], age ≥ 45 years [aPR: 4.23, 95% CI: 2.206-8.108, P < 0.001] and 35-44 years [aPR: 2.455, 95% CI: 1.216-4.947, P < 0.012] as compared with age < 35 years, BMI ≥ 25 kg/m3 [aPR: 1.489, 95% CI: 1.072-2.067, P = 0.017] as compared with BMI < 25 kg/m3, duration on dolutegravir-based ART [aPR: 1.008, 95% CI: 1.001-1.015, P = 0.037], family history of hypertension [aPR: 1.457, 95% CI: 1.064-1.995, P = 0.019] and history of heart disease [aPR: 1.73, 95% CI: 1.205-2.484, P = 0.003] were associated with hypertension. One in every four people with HIV (PWH) on dolutegravir-based ART has hypertension. We recommend the integration of hypertension management in the HIV treatment package and policies to improve existing supply chains for low cost and high-quality hypertension medications.

Culturally adapting a mindfulness and acceptance-based intervention to support the mental health of adolescents on antiretroviral therapy in Uganda.

The dual burden of living with HIV and negotiating life stage changes has been identified as a contributing factor to lapsed adherence among adolescents with HIV in sub-Saharan Africa. While psychosocial support can promote medication adherence, most interventions in use with adolescents were originally developed for the general population creating a gap in appropriate support. Life-stage-appropriate, evidence-based psychosocial support interventions have been used with young people in high-income contexts, prompting interest in their use in low-income contexts. However, many interventions are less effective when implemented outside of their original settings, hence the need for modifications before implementation. We aimed to culturally adapt an evidence-based psychosocial support intervention designed to improve the mental health of young people for use among adolescents with HIV in a sub-Saharan African context and to explore the acceptability of the adapted intervention among adolescents. We engaged thirty stakeholders (n = 30) in Kampala, Uganda including psychologists, psychiatrists, social workers, HIV counselors, religious leaders and adolescent peers from December 2021 to April 2022 to modify an evidence-based intervention for adolescents. Key adaptations included simplifying the language, adding local practices, integrating locally relevant slang and stories into therapy, introducing racially-congruent visuals and cards representing emotions, and adjusting therapy materials for use in resource-constrained settings. We then tested the acceptability of the intervention in a small sample of service users using a qualitative approach. We recruited nine adolescents with HIV from a participating clinic in Kampala, delivered six 90-minute sessions of the adapted intervention across three weeks and conducted in-depth interviews to assess the acceptability of the intervention. We used thematic analysis to analyze the qualitative data. The adapted intervention was perceived as acceptable among adolescents with HIV, with many stating that it helped them overcome fears, increased their self-acceptance, and gave them the confidence to make careful health-enhancing decisions.

Prevalence and incidence of hypertension in a heavily treatment-experienced cohort of people living with HIV in Uganda.

The effect of long-term exposure to antiretroviral therapy (ART) on hypertension in sub-Saharan Africa remains unclear. We aimed to determine the prevalence and incidence of hypertension in people living with HIV (PLWH) with more than 10 years of ART in Uganda. The analysis was performed within a cohort of adult PLWH with more than 10 years of ART at an HIV clinic in Kampala, Uganda. Participants were eligible for this analysis if they had ≥2 follow-up visits. Hypertension was defined as two consecutive systolic blood pressure (SBP) measures greater than 140 mmHg and/or diastolic blood pressure (DBP) greater than 90 mmHg, and/or documented diagnosis and/or the initiation of antihypertensives. We determined the proportion of PLWH with hypertension at baseline and used multivariable logistic regression to determine the factors associated with prevalent hypertension. To determine the incidence of hypertension, follow-up began from the cohort baseline date and was censored at the last clinic visit or date of the event, whichever occurred earlier. Multivariable Poisson regression was used to determine the adjusted incidence rate ratios (aIRR) of hypertension according to demographic, ART, and clinical characteristics. Of the 1000 ALT participants, 970 (97%) had ≥2 follow-up visits, and 237 (24.4%) had hypertension at baseline. The odds of prevalent hypertension were 1.18 for every 5-year increase in age (adjusted odds ratio (aOR) 1.18, 95% CI 1.10-1.34) and were higher among males (aOR 1.70, 95% CI 1.20-2.34), participants with diabetes mellitus (aOR 2.37, 95% CI 1.10-4.01), obesity (aOR 1.99, 95% CI 1.08-3.60), high cholesterol (aOR 1.47, 95% CI 1.16-2.01), and those with prior exposure to stavudine (aOR 2.10, 95% CI 1.35-3.52), or nevirapine (aOR 1.90, 95% CI 1.25-3.01). Of the 733 participants without hypertension at baseline, 116 (15.83%) developed hypertension during 4671.3 person-years of follow-up (incidence rate 24.8 per 1000 person-years; 95% CI 20.7-29.8). The factors associated with incident hypertension were obesity (adjusted incidence rate ratio (aIRR) 1.80, 95% CI 1.40-2.81), older age (aIRR 1.12 per 5-year increase in age, 95% CI 1.10,1.25), and renal insufficiency (aIRR1.80, 95% CI 1.40-2.81). The prevalence and incidence of hypertension were high in this heavily treated PLWH cohort. Therefore, with increasing ART coverage, HIV programs in SSA should strengthen the screening for hypertension in heavily treated PLWH.

Point-of-care urine tenofovir testing to predict HIV drug resistance among individuals with virologic failure.

We sought to evaluate the utility of a point-of-care (POC) urine tenofovir (TFV) assay, developed to objectively assess adherence, to predict HIV drug resistance (HIVDR) in people failing first-line antiretroviral therapy (ART). We retrospectively analyzed TFV levels as a biomarker of adherence in urine specimens collected during a clinical trial that enrolled adults with virologic failure on first-line ART in Uganda and South Africa. Urine specimens were analyzed from participants on TFV-containing regimens who had a viral load >1000 copies/ml and paired genotypic resistance test (GRT) results. We assessed recent ART TFV adherence with a qualitative POC lateral flow urine assay with a cut-off value of 1500 ng/ml. We then calculated performance characteristics of the POC urine TFV assay to predict HIVDR, defined as intermediate or high-level resistance to any component of the current ART regimen. Urine specimens with paired plasma GRT results were available from 283 participants. The most common ART regimen during study conduct was emtricitabine, tenofovir disoproxil fumarate, and efavirenz. The overall prevalence of HIVDR was 86% ( n = 243/283). Of those with TFV detected on the POC assay, 91% ( n = 204/224) had HIVDR, vs. only 66% ( n = 39/59) among those with no TFV detected ( P- value < 0.001). Positive and negative predictive values of the assay to predict HIVDR were 91% and 34%, respectively. In populations with a high prevalence of HIVDR, the POC urine TFV assay can provide a low-cost, rapid method to guide requirements for confirmatory resistance testing and inform the need for regimen change.

Patient satisfaction among persons living with HIV/AIDS and receiving antiretroviral therapy in urban Uganda: A factor analysis.

Patient satisfaction is an important predictor of health outcomes among patients in HIV/AIDS treatment and care, yet it is rarely measured in routine clinic settings in most of Africa. The aims of our study were to evaluate the internal validity and reliability of the Consumer Assessment of Healthcare Providers and Systems instrument for measuring satisfaction, assess the general level of patient satisfaction, and identify the factors associated with the level of satisfaction among patients receiving antiretroviral therapy in Uganda. We conducted a cross-sectional study of 475 HIV/AIDS-infected patients from July to August 2015 in Kampala, Uganda. Eligible participants were 18 years or older, consented to the study and receiving antiretroviral therapy and outpatient care at the selected public health clinic. This study used a modified version of the validated Consumer Assessment of Healthcare Providers and Systems (CAHPS) instrument to assess the level of satisfaction among HIV/AIDS patients receiving outpatient care. We collected data on socio-demographics, clinical variables and 18-items adapted from the CAHPS instrument rating satisfaction with aspects of health services. We conducted an exploratory factor analysis to assess the internal validity of the 18 items and multiple linear regression analysis of factors associated with patient satisfaction with care. Majority of the respondents were females (76.8%), and the mean age was 37 years (SD = 10). The modified CAHPS instrument had high internal consistency (Cronbach's α = 0.94) for measuring satisfaction with HIV/AIDS care. Female sex (p = 0.016), perceived providers' technical and interpersonal skills (p = 0.022), emotional health (p = 0.032), and quality of reception services (p<0.001) were significantly associated with satisfaction in this urban HIV/AIDS public clinic. The reliability of the CAHPS instrument was high for measuring satisfaction. Providers' technical and interpersonal skills, and the quality of reception services are key to achieving patient satisfaction. Health system interventions to address the gaps identified will enhance the quality of patient-centered HIV/AIDS care in the Ugandan setting.

A Qualitative Exploration of Causes of Depression among Persons Living with HIV Receiving Antiretroviral Therapy in Uganda: Implications for Policy.

Depression is the fourth leading cause of the global disease burden and worsens the outcome of comorbidities including HIV/AIDS. Depression is particularly problematic among persons living with HIV in sub-Saharan Africa where scarcity of cost-effective interventions is compounded by inadequate understanding of the disease. We examine risk factors for depression among persons living with HIV undergoing antiretroviral treatment in Uganda and discuss policy implications. A qualitative study using a narrative approach was conducted, the formative phase of a large study to develop a model for integrating depression management into routine HIV care in Uganda. Participants were purposively sampled at four public health facilities in Mpigi District. In-depth interviews were conducted with four clinicians, three supervisors, and 11 persons living with HIV and suffering from depression, as were three focus group discussions with lay health workers. Exit interviews were conducted with 17 persons living with HIV who completed/interrupted depression treatment but had not been interviewed. Only data collected from persons living with HIV and lay health workers were analysed for the purpose of this paper. A narrative thematic approach was used in data analysis. Findings. There were several pathways through which lack of family social support reportedly led to depression: worries about disclosure in discordant relationships, false perceptions of social support, stigmatisation and discrimination, and domestic violence. Economic/poverty and other causes were identified, but their role was less significant or moderated by family social support. Family social support plays a dominant role-both directly and indirectly-in influencing depression risk. We propose the mainstreaming of formal psychosocial support and a shift from individual to family-focused counselling that targets both persons living with HIV and their family.

The association between low-level viraemia and subsequent viral non-suppression among people living with HIV/AIDS on antiretroviral therapy in Uganda.

Uganda's efforts to end the HIV epidemic by 2030 are threatened by the increasing number of PLHIV with low-level viraemia (LLV). We conducted a study to determine the prevalence of LLV and the association between LLV and subsequent viral non-suppression from 2016 to 2020 among PLHIV on ART in Uganda. This was a retrospective cohort study, using the national viral load (VL) program data from 2016 to 2020. LLV was defined as a VL result of at least 50 copies/ml, but less than 1,000 copies/ml. Multivariable logistic regression was used to determine the factors associated with LLV, and cox proportional hazards regression model was used to determine the association between LLV and viral non-suppression. A cohort of 17,783 PLHIV, of which 1,466 PLHIV (8.2%) had LLV and 16,317 (91.8%) had a non-detectable VL was retrospectively followed from 2016 to 2020. There were increasing numbers of PLHIV with LLV from 2.0% in 2016 to 8.6% in 2020; and LLV was associated with male sex, second line ART regimen and being of lower age. 32.5% of the PLHIV with LLV (476 out of 1,466 PLHIV) became non-suppressed, as compared to 7.7% of the PLHIV (1,254 out of 16,317 PLHIV) with a non-detectable viral load who became non-suppressed during the follow-up period. PLHIV with LLV had 4.1 times the hazard rate of developing viral non-suppression, as compared to PLHIV with a non-detectable VL (adjusted hazard ratio was 4.1, 95% CI: 3.7 to 4.7, p < 0.001). Our study indicated that PLHIV with LLV increased from 2.0% in 2016 to 8.6% in 2020, and PLHIV with LLV had 4.1 times the hazard rate of developing viral non-suppression, as compared to PLHIV with a non-detectable VL. Hence the need to review the VL testing algorithm and also manage LLV in Uganda.

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

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

Adherence monitoring methods to measure virological failure in people living with HIV on long-term antiretroviral therapy in Uganda.

Appointment keeping and self-report within 7-day or and 30-days recall periods are non-objective measures of antiretroviral treatment (ART) adherence. We assessed incidence of virological failure (VF), predictive performance and associations of these adherence measures with VF among adults on long-term ART. Data for persons initiated on ART between April 2004 and April 2005, enrolled in a long-term ART cohort at 10-years on ART (baseline) and followed until December 2021 was analyzed. VF was defined as two consecutives viral loads ≥1000 copies/ml at least within 3-months after enhanced adherence counselling. We estimated VF incidence using Kaplan-Meier and Cox-proportional hazards regression for associations between each adherence measure (analyzed as time-dependent annual values) and VF. The predictive performance of appointment keeping and self-reporting for identifying VF was assessed using receiver operating characteristic curves and reported as area under the curve (AUC). We included 900 of 1,000 participants without VF at baseline: median age was 47 years (Interquartile range: 41-51), 60% were women and 88% were virally suppressed. ART adherence was ≥95% for all three adherence measures. Twenty-one VF cases were observed with an incidence rate of 4.37 per 1000 person-years and incidence risk of 2.4% (95% CI: 1.6%-3.7%) over the 5-years of follow-up. Only 30-day self-report measure was associated with lower risk of VF, adjusted hazard ratio (aHR) = 0.14, 95% CI:0.05-0.37). Baseline CD4 count ≥200cells/ml was associated with lower VF for all adherence measures. The 30-day self-report measure demonstrated the highest predictive performance for VF (AUC = 0.751) compared to appointment keeping (AUC = 0.674), and 7-day self-report (AUC = 0.687). The incidence of virological failure in this study cohort was low. Whilst 30- day self-report was predictive, appointment keeping and 7-day self-reported adherence measures had low predictive performance in identifying VF. Viral load monitoring remains the gold standard for adherence monitoring and confirming HIV treatment response.

Prevalence of neuropsychiatric adverse events and associated factors among adult patients on dolutegravir attending Mulago ISS clinic.

Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor that is recommended by the World Health Organization as the preferred first-line and second-line antiretroviral therapy (ART) in patients with HIV. In 2018, Uganda started using DTG-based regimens as the preferred first-line ART. However, concerns regarding the potential neurotoxicity of DTG have been increasing. Data on the occurrence of neuropsychiatric adverse events (NPAEs) and the associated factors among adult patients who are initiated on or switched to DTG-based first-line or second-line ART in Uganda are limited. This study aimed to determine the prevalence of NPAEs among adult patients on DTG and the factors associated with their occurrence. We conducted a cross-sectional study using questionnaires administered by a trained research assistant between 15 November 2021 and 15 December 2021. The study included patients aged ≥18 years with HIV who were either initiated on or switched to a DTG-based ART regimen between 1 January 2018 and 31 October 2021. Informed consent and data were collected from 892 participants attending Mulago ISS clinic, including data on age, sex, marital status, disclosure status, current regimen, duration on ART, concurrent illness, concurrent medications, year of switch to DTG, duration on DTG, whether the onset of NPAEs was immediate or delayed, history of alcohol use or smoking, level of education, report of NPAEs while on DTG, and history of NPAEs while on previous regimen. Data were entered into Epidata version 4.6.0.2 then exported to Stata version 14 for analysis. Of the 892 adults on DTG attending Mulago ISS clinic, 41.7% (95% confidence interval [CI] 38.5%-44.9%) experienced at least one NPAE. DTG duration in years (adjusted prevalence [aPR]=1.21, p=0.024), disclosure status (aPR=1.40, p=0.042), concurrent medications (aPR=1.31, p=0.026), year of switch to DTG, and concurrent illness were associated with an increased occurrence of NPAEs. The prevalence of NPAEs was higher than that reported by any clinical trial. About 9.1% of participants had experienced severe to life-threatening NPAEs that required intervention from a healthcare professional to improve tolerability. The high prevalence requires that clinicians screen for NPAEs at very visit and reassure patients to maximize the benefits of long-term ART.

Real-time Feedback to Improve HIV Treatment Adherence in Pregnant and Postpartum Women in Uganda: A Randomized Controlled Trial

We assessed an intervention aimed at improving adherence to antiretroviral therapy (ART) among pregnant and postpartum women living with HIV (PPWLH). We randomized 133 pregnant women initiating ART in Uganda to receive text reminders generated by real time-enabled electronic monitors and data-informed counseling through 3 months postpartum (PPM3) or standard care. Intention-to-treat analyses found low adherence levels and no intervention impact. Proportions achieving ≥95% adherence in PPM3 were 16.4% vs. 9.1% (t = -1.14, p = 0.26) in intervention vs. comparison groups, respectively; 30.9% vs. 29.1% achieved ≥80% adherence. Additional analyses found significant adherence declines after delivery, and no effect on disease progression (CD4-cell count, viral load), though treatment interruptions were significantly fewer in intervention participants. Per-protocol analyses encompassing participants who used adherence monitors as designed experienced better outcomes, suggesting potential benefit for some PPWLH. The study was registered on ClinicalTrials.Gov (NCT02396394).

Prevalence, correlates and treatment needs of dental caries among people on antiretroviral therapy in Uganda: a cross sectional study

BackgroundOral diseases are estimated to affect half of people living with HIV in the western world, and are often marked by pain, discomfort, disfigurement and reduced quality of life. Both HIV-specific and antiretroviral therapy-associated oral diseases have been found in this population. However, the prevalence, correlates and treatment needs of dental caries among people on antiretroviral therapy has not been well studied in rural Africa where majority of people living with HIV reside. Moreover, health behaviors and access to dental care vary significantly from high-income countries in the global north.MethodsA cross-sectional study was conducted among people living with HIV attending a high-volume HIV clinic with an enrollment of 10,000 patients in a regional referral hospital in Southwestern Uganda. The clinic is located in an urban setting with a large rural catchment area. Oral health data was collected using the modified World Health Organization oral health questionnaire for adults. Dental examinations were conducted to identify and classify dental caries using the decayed, missing, filled, teeth (DMFT) index and compute the treatment need. Logistic regression models were employed to identify correlate of dental caries.ResultsA total of 194 participants were included in the study. The majority were female (124/194, 63.9%) with a median age of 42 years (IQR 36–49). The prevalence of dental caries experience among study participants was 67%, (130/194, 95% CI 60–75%). The mean DMFT index score was 4 (IQR 2–6) and treatment need was 96% (192/200). A higher CD4 count was associated with the presence of dental caries (OR 0.403, 95% CI 0.175–0.932) although it was not significant in multivariate analysis.ConclusionThere is a high prevalence of dental caries among people living with HIV on ART in Uganda. Our data demonstrate a high oral treatment need among this population. We recommend inclusion of preventive and therapeutic oral care into HIV care in this region.

Evaluation of the initial 12\u2009months of a routine cryptococcal antigen screening program in reduction of HIV-associated cryptococcal meningitis in Uganda

BackgroundAsymptomatic Cryptococcal Antigenemia (CrAg) patients develop meningitis within a month of testing positive. Pre-emptive antifungal therapy can prevent progression to Cryptococcal meningitis (CM). In April 2016, a national CrAg screening program was initiated in 206 high-volume health facilities that provide antiretroviral therapy in Uganda. We report the evaluation of the CrAg screening cascade focusing on linkage to care, fluconazole therapy for 10 weeks and 6 months follow up, and ART initiation in a subset of facilities.MethodsWe conducted a retrospective, cross-sectional survey of patients with CD4 < 100 at seven urban and seven rural facilities after 1 year of program implementation. We quantified the number of patients who transitioned through the steps of the CrAg screening cascade over six-months follow-up. We defined cascade completion as a pre-emptive fluconazole prescription for the first 10 weeks. We conducted semi-structured interviews with lab personnel and clinic staff to assess functionality of the CrAg screening program. Data was collected using REDCap.ResultsWe evaluated 359 patient records between April 2016 to March 2017; the majority (358/359, 99.7%) were from government owned health facilities and just over half (193/359, 53.8%) had a median baseline CD4 cell count of < 50 cell/μL. Overall, CrAg screening had been performed in 255/359 (71.0, 95% CI, 66.0–75.7) of patients’ records reviewed, with a higher proportion among urban facilities (170/209 (81.3, 95% CI, 75.4–86.4)) than rural facilities (85/150 (56.7, 95% CI, 48.3–64.7)). Among those who were CrAg screened, 56/255 (22.0, 95% CI, 17.0–27.5%) had cryptococcal antigenemia, of whom 47/56 (83.9, 95% CI, 71.7–92.4%) were initiated on pre-emptive therapy with fluconazole and 8/47 (17.0, 95% CI, 7.6–30.8%) of these were still receiving antifungal therapy at 6 months follow up. At least one CNS symptom was present in 70% (39/56) of those with antigenemia. In patients who had started ART, almost 40% initiated ART prior to CrAg screening. Inadequacy of equipment/supplies was reported by 15/26 (58%) of personnel as a program barrier, while 13/26 (50%) reported a need for training about CM and CrAg screening.ConclusionThere was a critical gap in the follow-up of patients after initiation on fluconazole therapy. ART had been initiated in almost 40% of patients prior to CrAg screening.. Higher antigenemia patients presenting with CNS symptoms could be related to late presentation. There is need to address these gaps after a more thorough evaluation.

Resumption of Sexual Intercourse Among Postnatal Women Enrolled on Lifelong Antiretroviral Therapy in Uganda.

The postnatal period is critical to the delivery of interventions aimed at improving maternal health outcomes. This study examined the timing to resumption of sexual intercourse and associated factors among postnatal women living with HIV (WLWH) in Uganda. A sample of 385 women was drawn from a larger prospective cohort study conducted between 2013 and 2015. We used survival analysis to estimate the postpartum time periods during which women had a higher risk of sexual intercourse resumption within 6 months after childbirth. Cox proportional hazards regression was used to examine associated factors with sexual intercourse resumption. The cumulative probability of sexual intercourse resumption was lowest (6.2%) in the sub-acute postpartum period (1-45days since delivery) and highest (88.2%) in the delayed postpartum period (151-183days since delivery). Having a live-term baby (adjusted HR 0.52, 95% CI 0.31-0.85, p = 0.01) and an advanced education (adjusted HR 0.63, 95% CI 0.40-0.98, p = 0.04) were associated with a lower risk of sexual intercourse resumption. Desire for another child (adjusted HR 1.36, 95% CI 1.08-1.73, p = 0.01), having a sexual partner (adjusted HR 5.97, 95% CI 3.10-11.47, p < 0.001) and contraceptive use (adjusted HR 2.21, 95% CI 1.65-2.95, p < 0.001) were associated with a greater risk of sexual intercourse resumption. However, only 1 in 4 women who resumed sexual intercourse by the 90th day after childbirth, reported currently using contraception. HIV programs should focus on supporting postnatal women to align the timing of sexual intercourse resumption with their return to contraceptive use. Interventions aimed at improving contraceptive uptake among postnatal WLWH should target the delayed postpartum period.