Treatment Outcomes for Tuberculosis Infection and Disease Among Persons Deprived of Liberty, Uganda, 2020.

We report that unsuccessful treatment outcomes were 11.8% for tuberculosis (TB) disease and 21.8% for TB infection among persons deprived of liberty in Uganda Prisons Service facilities. Remedial efforts should include enhancing referral networks to ensure treatment continuity, strengthening data systems for complete outcome documentation, and prioritizing short-course treatment regimens.

Provision of cervical cancer services for women living with HIV, Uganda.

Objective: To describe the scale-up of cervical cancer screening and treatment for women living with human immunodeficiency virus (HIV), aged 25-49 years in Uganda, and to analyse the programme data. Methods: The health ministry targeted existing HIV clinics in a 2-year scale-up of cervical cancer screening services from October 2020. In preparation, we trained health workers to assess women attending HIV clinics for screening eligibility, provided either by human papillomavirus (HPV) testing and/or visual inspection with acetic acid. Clinic staff treated women with precancerous cervical lesions with thermocoagulation or referred women with suspected cancer to external services. We analysed data reported every 6 months for the number of clinics offering screening, screening uptake, the number of positive diagnoses and the number of women who received treatment. Findings: The number of HIV clinics offering cervical cancer screening services increased from 11, before the programme launch, to 1571. During the programme, screening uptake increased from 5.0% (6506/130 293) to 107.3% (151 872/141 527) of targets. The cumulative proportion of positive diagnoses was 5.9% (23 970/407 323) overall, but was much lower for screening offering visual inspection only compared with clinics offering HPV testing. Although the proportion of women receiving treatment if positive increased from 12.8% (53/413) to 84.3% (8087/9592), the World Health Organization target of 90% was not reached. Conclusion: We demonstrated marked increases, potentially replicable by other countries, in screening and treatment. These increases could be improved further by expanding HPV testing and same-day treatment of precancerous lesions.

Cervical Cancer Screening Positivity Among Women Living With HIV in CDC-PEPFAR Programs 2018-2022.

BACKGROUND: The US President's Emergency Plan for AIDS Relief aims to address the higher risk of cervical cancer among women living with HIV by offering high-quality screening services in the highest burden regions of the world. METHODS: We analyzed the US President's Emergency Plan for AIDS Relief Monitoring, Evaluation, and Reporting data from Centers for Disease Control and Prevention-supported sites in 13 countries in sub-Saharan Africa for women living with HIV aged older than 15 years who accessed cervical cancer screening services (mostly visual inspection, with ablative or excisional treatment offered for precancerous lesions), April 2018-March 2022. We calculated the positivity by age, country, and clinical visit type (first lifetime screen or routine rescreening). We fitted negative binomial random coefficient models of log-linear trends in time to estimate the probabilities of testing positive and any temporal trends in positivity. RESULTS: Among the 2.8 million completed cancer screens, 5.4% identified precancerous lesions, and 0.8% were positive for suspected invasive cervical cancers (6.1% overall). The positivity rates declined over the study period among those women screening for cervical cancer for the first time and among those women presenting to antiretroviral therapy clinics for routine rescreening. CONCLUSIONS: These positivity rates are lower than expectations set by the published literature. Further research is needed to determine whether these lower rates are attributable to the high level of consistent antiretroviral therapy use among these populations, and systematic program monitoring and quality assurance activities are essential to ensure women living with HIV have access to the highest possible quality prevention services.

High blood pressure and associated factors among HIV-infected young persons aged 13 to 25 years at selected health facilities in Rwenzori region, western Uganda, September-October 2021.

BACKGROUND: High blood pressure (HBP), including hypertension (HTN), is a predictor of cardiovascular events, and is an emerging challenge in young persons. The risk of cardiovascular events may be further amplified among people living with HIV (PLHIV). We determined the prevalence of HBP and associated factors among PLHIV aged 13 to 25 years in Rwenzori region, western Uganda. METHODS: We conducted a cross-sectional study among PLHIV aged 13 to 25 years at nine health facilities in Kabarole and Kasese districts during September 16 to October 15, 2021. We reviewed medical records to obtain clinical and demographic data. At a single clinic visit, we measured and classified BP as normal (< 120/ < 80 mmHg), elevated (120/ < 80 to 129/ < 80), stage 1 HTN (130/80 to 139/89), and stage 2 HTN (≥ 140/90). We categorized participants as having HBP if they had elevated BP or HTN. We performed multivariable analysis using modified Poisson regression to identify factors associated with HBP. RESULTS: Of the 1,045 PLHIV, most (68%) were female and the mean age was 20 (3.8) years. The prevalence of HBP was 49% (n = 515; 95% confidence interval [CI], 46%-52%), the prevalence of elevated BP was 22% (n = 229; 95% CI, 26%-31%), and the prevalence of HTN was 27% (n = 286; 95% CI, 25%-30%), including 220 (21%) with stage 1 HTN and 66 (6%) with stage 2 HTN. Older age (adjusted prevalence ratio [aPR], 1.21; 95% CI, 1.01-1.44 for age group of 18-25 years vs. 13-17 years), history of tobacco smoking (aPR, 1.41; 95% CI, 1.08-1.83), and higher resting heart rate (aPR, 1.15; 95% CI, 1.01-1.32 for > 76 beats/min vs. ≤ 76 beats/min) were associated with HBP. CONCLUSIONS: Nearly half of the PLHIV evaluated had HBP, and one-quarter had HTN. These findings highlight a previously unknown high burden of HBP in this setting's young populations. HBP was associated with older age, elevated resting heart rate, and ever smoking; all of which are known traditional risk factors for HBP in HIV-negative persons. To prevent future cardiovascular disease epidemics among PLHIV, there is a need to integrate HBP/HIV management.

Tuberculosis Preventive Therapy among Persons Living with HIV, Uganda, 2016-2022.

During October 2016-March 2022, Uganda increased tuberculosis (TB) preventive therapy coverage among persons living with HIV from 0.6% to 88.8%. TB notification rates increased from 881.1 to 972.5 per 100,000 persons living with HIV. Timely TB screening, diagnosis, and earlier treatment should remain high priorities for TB/HIV prevention programming.

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.

Cryptococcal Antigenemia in Human Immunodeficiency Virus Antiretroviral Therapy-Experienced Ugandans With Virologic Failure.

BACKGROUND: Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus-positive persons with CD4 count <100 cells/µL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown. METHODS: We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017-January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review. RESULTS: Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10-84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8-19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads <5000 copies/mL. CONCLUSIONS: In addition to the CD4 threshold of <100 cells/µL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL.

Anti-tuberculosis drug resistance among new and previously treated sputum smear-positive tuberculosis patients in Uganda: results of the first national survey.

BACKGROUND: Multidrug resistant and extensively drug resistant tuberculosis (TB) have become major threats to control of tuberculosis globally. The rates of anti-TB drug resistance in Uganda are not known. We conducted a national drug resistance survey to investigate the levels and patterns of resistance to first and second line anti-TB drugs among new and previously treated sputum smear-positive TB cases. METHODS: Sputum samples were collected from a nationally representative sample of new and previously treated sputum smear-positive TB patients registered at TB diagnostic centers during December 2009 to February 2011 using a weighted cluster sampling method. Culture and drug susceptibility testing was performed at the national TB reference laboratory. RESULTS: A total of 1537 patients (1397 new and 140 previously treated) were enrolled in the survey from 44 health facilities. HIV test result and complete drug susceptibility testing (DST) results were available for 1524 (96.8%) and 1325 (85.9%) patients, respectively. Of the 1209 isolates from new cases, resistance to any anti-TB drug was 10.3%, 5% were resistant to isoniazid, 1.9% to rifampicin, and 1.4% were multi drug resistant. Among the 116 isolates from previously treated cases, the prevalence of resistance was 25.9%, 23.3%, 12.1% and 12.1% respectively. Of the 1524 patients who had HIV testing 469 (30.7%) tested positive. There was no association between anti-TB drug resistance (including MDR) and HIV infection. CONCLUSION: The prevalence of anti-TB drug resistance among new patients in Uganda is low relative to WHO estimates. The higher levels of MDR-TB (12.1%) and resistance to any drug (25.3%) among previously treated patients raises concerns about the quality of directly observed therapy (DOT) and adherence to treatment. This calls for strengthening existing TB control measures, especially DOT, routine DST among the previously treated TB patients or periodic drug resistance surveys, to prevent and monitor development and transmission of drug resistant TB.

Protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children in rural Uganda: a randomised clinical trial.

OBJECTIVE: To evaluate the protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children (uninfected children born to HIV infected mothers) in Africa. DESIGN: Non-blinded randomised control trial SETTING: Tororo district, rural Uganda, an area of high malaria transmission intensity PARTICIPANTS: 203 breastfeeding HIV exposed infants enrolled between 6 weeks and 9 months of age INTERVENTION: Co-trimoxazole prophylaxis from enrollment until cessation of breast feeding and confirmation of negative HIV status. All children who remained HIV uninfected (n = 185) were then randomised to stop co-trimoxazole prophylaxis immediately or continue co-trimoxazole until 2 years old. MAIN OUTCOME MEASURE: Incidence of malaria, calculated as the number of antimalarial treatments per person year. RESULTS: The incidence of malaria and prevalence of genotypic mutations associated with antifolate resistance were high throughout the study. Among the 98 infants randomised to continue co-trimoxazole, 299 malaria cases occurred in 92.28 person years (incidence 3.24 cases/person year). Among the 87 infants randomised to stop co-trimoxazole, 400 malaria cases occurred in 71.81 person years (5.57 cases/person year). Co-trimoxazole prophylaxis yielded a 39% reduction in malaria incidence, after adjustment for age at randomisation (incidence rate ratio 0.61 (95% CI 0.46 to 0.81), P = 0.001). There were no significant differences in the incidence of complicated malaria, diarrhoea, pneumonia, hospitalisations, or deaths between the two treatment arms. CONCLUSIONS: Co-trimoxazole prophylaxis was moderately protective against malaria in HIV exposed infants when continued beyond the period of HIV exposure despite the high prevalence of Plasmodium genotypes associated with antifolate resistance. Trial registration Clinical Trials NCT00527800.

Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children.

BACKGROUND: Artemisinin-based combination therapies are now widely recommended as first-line treatment for uncomplicated malaria. However, which therapies are optimal is a matter of debate. We aimed to compare the short- and longer-term efficacy of 2 leading therapies in a cohort of young Ugandan children. METHODS: A total of 351 children aged 6 weeks to 12 months were enrolled and followed up for up to 1 year. Children who were at least 4 months of age, weighted at least 5 kg, and had been diagnosed as having their first episode of uncomplicated malaria were randomized to receive artemether-lumefantrine or dihydroartemisinin-piperaquine. The same treatment was given for all subsequent episodes of uncomplicated malaria. Recrudescent and new infections were distinguished by polymerase chain reaction genotyping. Outcomes included the risk of recurrent malaria after individual treatments and the incidence of malaria treatments for individual children after randomization. RESULTS: A total of 113 children were randomized to artemether-lumefantrine and 119 to dihydroartemisinin-piperaquine, resulting in 320 and 351 treatments for uncomplicated falciparum malaria, respectively. Artemether-lumefantrine was associated with a higher risk of recurrent malaria after 28 days (35% vs 11%; P = .001]). When the duration of follow-up was extended, differences in the risk of recurrent malaria decreased such that the overall incidence of malaria treatments was similar for children randomized to artemether-lumefantrine, compared with those randomized to dihydroartemisinin-piperaquine (4.82 vs 4.61 treatments per person-year; P = .63). The risk of recurrent malaria due to recrudescent parasites was similarly low in both treatment arms. CONCLUSIONS: Artemether-lumefantrine and dihydroartemisinin-piperaquine were both efficacious and had similar long-term effects on the risk of recurrent malaria. Clinical trials registration. NCT00527800.

Routine intrapartum HIV counseling and testing for prevention of mother-to-child transmission of HIV in a rural Ugandan hospital.

OBJECTIVE: In Africa, prevention of mother-to-child HIV transmission (PMTCT) programs are hindered by limited uptake by women and their male partners. Routine HIV counseling and testing (HCT) during labor has been proposed as a way to increase PMTCT uptake, but little data exist on the impact of such intervention in a programmatic context in Africa. DESIGN AND METHODS: In May 2004, PMTCT services were established in the antenatal clinic (ANC) of a 200-bed hospital in rural Uganda; in December 2004, ANC PMTCT services became opt-out, and routine opt-out intrapartum HCT was established in the maternity ward. We compared acceptability, feasibility, and uptake of maternity and ANC PMTCT services between December 2004 and September 2005. RESULTS: HCT acceptance was 97% (3591/3741) among women and 97% (104/107) among accompanying men in the ANC and 86% (522/605) among women and 98% (176/180) among their male partners in the maternity. Thirty-four women were found to be HIV seropositive through intrapartum testing, representing an 12% (34/278) increase in HIV infection detection. Of these, 14 received their result and nevirapine before delivery. The percentage of women discharged from the maternity ward with documented HIV status increased from 39% (480/1235) to 88% (1395/1594) over the period. Only 2.8% undocumented women had their male partners tested in the ANC in contrast to 25% in the maternity ward. Of all male partners who presented to either unit, only 48% (51/107) came together and were counseled with their wife in the ANC, as compared with 72% (130/180) in the maternity ward. Couples counseled together represented 2.8% of all persons tested in the ANC, as compared with 37% of all persons tested in the maternity ward. CONCLUSION: Intrapartum HCT may be an acceptable and feasible way to increase individual and couple participation in PMTCT interventions.