Relating CYP2B6 genotype and efavirenz resistance among post-partum women living with HIV with high viremia in Uganda: a nested cross-sectional study.

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.

HiSTEP: A Single-Arm Pilot Study of a Technology-Assisted HIV Self-testing Intervention in Kampala, Uganda.

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.

Impact of an intensive facility-community case management intervention on 6-month HIV outcomes among select key and priority populations in Uganda.

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.

Implementing screening for hypertension in archetypal HIV primary care: a mixed-methods assessment.

BACKGROUND: High prevalence of HIV and hypertension in sub-Saharan Africa puts adults living with HIV (ALWH) at high risk of end-organ complications. Both World Health Organization (WHO) and national guidelines recommend screening and treatment of hypertension among ALWH on antiretroviral therapy (ART). We evaluated the implementation of hypertension screening among adults on ART at three Uganda Cares Primary care facilities. METHODS: Using a sequential explanatory mixed-methods approach, we reviewed patient records, and interviewed both patients and providers during 2018 and 2019. We obtained demographics, clinical and blood pressure (BP) measurements via records review. We estimate the period prevalence of screening and use adjusted modified Poisson regression models to evaluate predictors of screening. In-depth interviews were analysed using a thematic approach to explain the observed prevalence and predictors of BP screening. RESULTS: Records for 1426 ALWH were reviewed. Patients had a median age of 35 years and 65% of them were female. Most were on ART (89% on first-line) with a median duration of 4 years. Only 262 (18%) were overweight or obese with a body mass index (BMI) > 25 Kg/M2. In 2017 or 2018 patients made a median of 3 visits and 783 patients had a BP recorded, hence a period prevalence 55%. Older age, male sex, more clinic visits, and clinic site were associated with screening in the adjusted analyses. Erratic BP screening was corroborated by patients' and providers' interviews. Challenges included; high patient numbers, low staffing, provider apathy, no access to treatment, and lack of functioning of BP equipment. CONCLUSION: Almost half of regular HIV clinic attendees at these prototypical primary care HIV clinics were not screened for hypertension for a whole year. Improving BP screening requires attention to address modifiable challenges and ensure local buy-in beyond just providing equipment.

The impact of geriatric syndromes on quality of life among older people living with HIV in Kampala, Uganda.

Objective: Older people living with HIV (OPWH) often have lower quality of life (QoL) compared to general population. Measuring their QoL is an important step in HIV care to ensure they have long healthy lives. This study aimed to evaluate the quality of life and its associated factors among people living with HIV aged 60 years and above in Uganda. Methods: We used a cross-sectional analysis of older people living with HIV (OPWH) enrolled in a prospective cohort from December 2020 - December 2021. Quality of life was assessed using the World Health Organisation QoL OLD instrument (WHOQOL-OLD). Linear regression model was used to determine associated factors. Results: Of the 500 participants enrolled, 51.2% were men and their median age was 64 years (IQR: 62 - 68). WHOQOL-OLD mean score (SD) was 90.1 (8.3) out of 120. Factors that increased overall QoL were (Coefficient [95% Confidence Interval]): being male 2.35 (1.21 - 3.73), having an income of ≥$1 1.30 (-0.16 - 2.76) and paradoxically having more than 2 non-communicable diseases 0.69 (-0.76 - 2.14) in the past, present and future domain of QoL. Those that decreased QoL in the overall and various domains included: an increasing number of geriatric syndromes, depression, pre-frailty, frailty, malnutrition, and low physical function. Conclusion: Our findings suggest that financial stability contributed to good QoL while geriatric syndromes decreased QoL for OPWH. Integrating the screening and management of geriatric syndromes into HIV care has the potential to improve the overall QoL of OPWH.

Chronic immune activation and accelerated immune aging among HIV-infected adults receiving suppressive antiretroviral therapy for at least 12 years in an African cohort.

Background: HIV-associated alterations innate and adaptive immune cell compartments are reminiscent of the process of immune aging. Objectives: We described immune aging phenotypes among ART-treated HIV-infected adults relative to age-matched HIV-negative counterparts. Methods: In a cross-sectional comparative study of HIV-infected adults with CD4≥500 cells/µl after at least 12 years of suppressive ART and age-and-gender-matched HIV-negative individuals, immune activation and immune aging phenotypes were measured, using multi-color flowcytometry. Results: ART-treated HIV-infected individuals had higher body mass index (P = 0.004), waist-hip circumference (P = 0.041), hip circumference (P < 0.001), and diastolic blood pressure (P = 0.012) and immune activation (CD4+CD38+HLADR+; median 4.15,IQR(1.030,14.6)] relative to the HIV-negative age-matched individuals [median 3.14,IQR(1.030, 6.68)]; P=0.0034. Immune aging markers [CD4+CD57+T-cells; median 13.00 IQR (0.45,64.1)] were higher among HIV-infected ART-treated adults<50 years relative to HIV-negative<50 years[median 8.020,IQR(0.004,21.2)]; P=0.0010. Naïve CD4 T-cells, Central memory CD4 T-cells, Terminal Effector Memory T cells (TEMRA: CD27-CD45RA + CCR7-) and immune senescence CD4/CD8+CD28-/CD57+ T-cells were similar among ART-treated HIV-infected individuals<45 years relative to 60 years-and-older HIV-negative counterparts≥; p = 0.0932, p = 0.05357, p = 0.0950 and p = 0.5714 respectively. Conclusion: ART-treated adults are immunologically two decades older than their HIV-negative counterparts. Accelerated immune aging among individuals aging with HIV underscores the need for an HIV cure to avert the unprecedented complications of accelerated immune senescence and the associated NCD risk in African settings with protracted exposure to endemic co-infections.

Clinical Predictors of 3-Months Isoniazid Rifapentine (3HP) - Related Adverse Drug Reactions (ADR) During Tuberculosis Preventive Therapy. (PAnDoRA-3HP study): An Observational Study Protocol.

Introduction: Tuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for Tuberculosis Preventive Therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs. Our study aims to describe the pharmacokinetic and pharmacogenomics of 3HP used for TPT, the ADRs and their association with completion rates, and TPT outcomes, providing vital insights for TB control strategies in resource-limited settings. Methods: This is an observational cohort study with a nested case-control study. We enrolled consecutive patients initiated on TPT using the 3HP regimen. These are followed up bi-weekly and then monthly during the active phase of treatment and 3 monthly for 2 years following completion of TPT. ADR evaluation includes clinical assessment and liver function tests. Cases are selected from those who experience ADRs, and controls from those who do not. Serum isoniazid and rifapentine concentrations are measured and pharmacogenomic analysis for NAT2 and CYP2E1 polymorphisms are done. Participants are followed up for 2 years to determine TPT outcomes. Analysis: The safety profile of 3HP will be assessed using descriptive statistics, including proportions of patients experiencing ADRs and grade 3 or above events related to treatment. Chi-square tests and regression models will determine predictors of ADRs and their impact on treatment completion. Pharmacokinetic-pharmacodynamic modeling will establish population parameters and factors influencing rifapentine and isoniazid concentrations.

Community purchases of antimicrobials during the COVID-19 pandemic in Uganda: An increased risk for antimicrobial resistance.

Self-Medication (SM) involves the utilization of medicines to treat self-recognized symptoms or diseases without consultation and the irrational use of over-the-counter drugs. During the COVID-19 pandemic, the lack of definitive treatment led to increased SM. We aimed to estimate the extent of SM for drugs used to treat COVID-19 symptoms by collecting data from pharmacy sale records. The study was conducted in Kampala, Uganda, where we extracted data from community pharmacies with functional Electronic Health Records between January 2018 and October 2021 to enable a comparison of pre-and post-COVID-19. The data included the number of clients purchasing the following drugs used to treat COVID-19 and its symptoms: Antibiotics included Azithromycin, Erythromycin, and Ciprofloxacin; Supplements included Zinc and vitamin C, while Corticosteroids included dexamethasone. A negative binomial model was used to estimate the incident rate ratios for each drug to compare the effect of COVID-19 on SM. In the pre- COVID-19 period (1st January 2018 to 11th March 2020), 19,285 customers purchased antibiotics which included; Azithromycin (n = 6077), Ciprofloxacin (n = 6066) and Erythromycin (n = 997); health supplements including Vitamin C (430) and Zinc (n = 138); and Corticosteroid including Dexamethasone (n = 5577). During the COVID-19 pandemic (from 15th March 2020 to the data extraction date in October 2021), we observed a 99% increase in clients purchasing the same drugs. The number of clients purchasing Azithromycin increased by 19.7% to 279, Ciprofloxacin reduced by 58.8% to 96 clients, and those buying Erythromycin similarly reduced by 35.8% to 492 clients. In comparison, there were increases of 170%, 181%, and 377% for Vitamin C, Zinc, and Dexamethasone, respectively. The COVID-19 pandemic underscored the extent of SM in Uganda. We recommend future studies with a representation of data from pharmacies located in rural and urban areas to further study pandemics' effect on antimicrobials prescriptions, including obtaining pharmacists' perspectives using mixed methods approaches.

Point-of-care testing for HIV and sexually transmitted infections reveals risky behavior among men at gambling centers in Uganda".

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.

Outcomes of retained and disengaged pregnant women living with HIV in Uganda.

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.