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.

Coronavirus Disease 2019 (COVID-19) Mitigation Efforts and Testing During an In-Person Training Event-Uganda, 12-29 October 2020.

Large public-health training events may result in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Universal SARS-CoV-2 testing during trainings for the Uganda Population-based HIV Impact Assessment identified 28 of 475 (5.9%) individuals with coronavirus disease 2019 (COVID-19) among attendees; most (89.3%) were asymptomatic. Until COVID-19 vaccine is readily available for staff and participants, effective COVID-19 mitigation measures, along with SARS-CoV-2 testing, are recommended for in-person trainings, particularly when trainees will have subsequent contact with survey participants.

HIV, syphilis, and hepatitis B virus infection and male circumcision in five Sub-Saharan African countries: Findings from the Population-based HIV Impact Assessment surveys, 2015-2019.

Voluntary medical male circumcision (VMMC) has primarily been promoted for HIV prevention. Evidence also supports that male circumcision offers protection against other sexually transmitted infections. This analysis assessed the effect of circumcision on syphilis, hepatitis B virus (HBV) infection and HIV. Data from the 2015 to 2019 Population-based HIV Impact Assessments (PHIAs) surveys from Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe were used for the analysis. The PHIA surveys are cross-sectional, nationally representative household surveys that include biomarking testing for HIV, syphilis and HBV infection. This is a secondary data analysis using publicly available PHIA data. Univariate and multivariable logistic regression models were created using pooled PHIA data across the five countries to assess the effect of male circumcision on HIV, active and ever syphilis, and HBV infection among sexually active males aged 15-59 years. Circumcised men had lower odds of syphilis infection, ever or active infection, and HIV, compared to uncircumcised men, after adjusting for covariates (active syphilis infection = 0.67 adjusted odds ratio (aOR), 95% confidence interval (CI), 0.52-0.87, ever having had a syphilis infection = 0.85 aOR, 95% CI, 0.73-0.98, and HIV = 0.53 aOR, 95% CI, 0.47-0.61). No difference between circumcised and uncircumcised men was identified for HBV infection (P = 0.75). Circumcised men have a reduced likelihood for syphilis and HIV compared to uncircumcised men. However, we found no statistically significant difference between circumcised and uncircumcised men for HBV infection.

Correcting for selection bias in HIV prevalence estimates: an application of sample selection models using data from population-based HIV surveys in seven sub-Saharan African countries.

INTRODUCTION: Population-based biomarker surveys are the gold standard for estimating HIV prevalence but are susceptible to substantial non-participation (up to 30%). Analytical missing data methods, including inverse-probability weighting (IPW) and multiple imputation (MI), are biased when data are missing-not-at-random, for example when people living with HIV more frequently decline participation. Heckman-type selection models can, under certain assumptions, recover unbiased prevalence estimates in such scenarios. METHODS: We pooled data from 142,706 participants aged 15-49 years from nationally representative cross-sectional Population-based HIV Impact Assessments in seven countries in sub-Saharan Africa, conducted between 2015 and 2018 in Tanzania, Uganda, Malawi, Zambia, Zimbabwe, Lesotho and Eswatini. We compared sex-stratified HIV prevalence estimates from unadjusted, IPW, MI and selection models, controlling for household and individual-level predictors of non-participation, and assessed the sensitivity of selection models to the copula function specifying the correlation between study participation and HIV status. RESULTS: In total, 84.1% of participants provided a blood sample to determine HIV serostatus (range: 76% in Malawi to 95% in Uganda). HIV prevalence estimates from selection models diverged from IPW and MI models by up to 5% in Lesotho, without substantial precision loss. In Tanzania, the IPW model yielded lower HIV prevalence estimates among males than the best-fitting copula selection model (3.8% vs. 7.9%). CONCLUSIONS: We demonstrate how HIV prevalence estimates from selection models can differ from those obtained under missing-at-random assumptions. Further benefits include exploration of plausible relationships between participation and outcome. While selection models require additional assumptions and careful specification, they are an important tool for triangulating prevalence estimates in surveys with substantial missing data due to non-participation.

HIV Incidence by Male Circumcision Status From the Population-Based HIV Impact Assessment Surveys-Eight Sub-Saharan African Countries, 2015-2017.

BACKGROUND: Male circumcision (MC) offers men lifelong partial protection from heterosexually acquired HIV infection. The impact of MC on HIV incidence has not been quantified in nationally representative samples. Data from the population-based HIV impact assessments were used to compare HIV incidence by MC status in countries implementing voluntary medical MC (VMMC) programs. METHODS: Data were pooled from population-based HIV impact assessments conducted in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe from 2015 to 2017. Incidence was measured using a recent infection testing algorithm and analyzed by self-reported MC status distinguishing between medical and nonmedical MC. Country, marital status, urban setting, sexual risk behaviors, and mean population HIV viral load among women as an indicator of treatment scale-up were included in a random-effects logistic regression model using pooled survey weights. Analyses were age stratified (15-34 and 35-59 years). Annualized incidence rates and 95% confidence intervals (CIs) and incidence differences were calculated between medically circumcised and uncircumcised men. RESULTS: Men 15-34 years reporting medical MC had lower HIV incidence than uncircumcised men [0.04% (95% CI: 0.00% to 0.10%) versus 0.34% (95% CI: 0.10% to 0.57%), respectively; P value = 0.01]; whereas among men 35-59 years, there was no significant incidence difference [1.36% (95% CI: 0.32% to 2.39%) versus 0.55% (95% CI: 0.14% to 0.67%), respectively; P value = 0.14]. DISCUSSION: Medical MC was associated with lower HIV incidence in men aged 15-34 years in nationally representative surveys in Africa. These findings are consistent with the expected ongoing VMMC program impact and highlight the importance of VMMC for the HIV response in Africa.

Unawareness of HIV Infection Among Men Aged 15-59 Years in 13 Sub-Saharan African Countries: Findings From the Population-Based HIV Impact Assessments, 2015-2019.

BACKGROUND: Identifying men living with HIV in sub-Saharan Africa (SSA) is critical to end the epidemic. We describe the underlying factors of unawareness among men aged 15-59 years who ever tested for HIV in 13 SSA countries. METHODS: Using pooled data from the nationally representative Population-based HIV Impact Assessments, we fit a log-binomial regression model to identify characteristics related to HIV positivity among HIV-positive unaware and HIV-negative men ever tested for HIV. RESULTS: A total of 114,776 men were interviewed and tested for HIV; 4.4% were HIV-positive. Of those, 33.7% were unaware of their HIV-positive status, (range: 20.2%-58.7%, in Rwanda and Cote d'Ivoire). Most unaware men reported they had ever received an HIV test (63.0%). Age, region, marital status, and education were significantly associated with HIV positivity. Men who had HIV-positive sexual partners (adjusted prevalence ratio [aPR]: 5.73; confidence interval [95% CI]: 4.13 to 7.95) or sexual partners with unknown HIV status (aPR: 2.32; 95% CI: 1.89 to 2.84) were more likely to be HIV-positive unaware, as were men who tested more than 12 months compared with HIV-negative men who tested within 12 months before the interview (aPR: 1.58; 95% CI: 1.31 to 1.91). Tuberculosis diagnosis and not being circumcised were also associated with HIV positivity. CONCLUSION: Targeting subgroups of men at risk for infection who once tested negative could improve yield of testing programs. Interventions include improving partner testing, frequency of testing, outreach and educational strategies, and availability of HIV testing where men are accessing routine health services.

Two-year follow-up of sexual behavior among HIV-uninfected household members of adults taking antiretroviral therapy in Uganda: no evidence of disinhibition.

This paper examines HIV risk behavior among HIV-uninfected adults living with people taking antiretroviral therapy (ART) in Uganda. A prospective cohort of 455 HIV-uninfected non-spousal household members of ART patients receiving home-based AIDS care was enrolled. Sexual behavior, HIV risk perceptions, AIDS-related anxiety, and the perception that AIDS is curable were assessed at baseline, 6, 12 and 24 months. Generalized linear mixture models were used to model risk behavior over time and to identify behavioral correlates. Overall, risky sex decreased from 29% at baseline to 15% at 24-months. Among women, risky sex decreased from 31% at baseline to 10% at 6 months and 15% at 24 months. Among men, risky sex decreased from 30% at baseline to 8% at 6 months and 13% at 24 months. Perceiving HIV/AIDS as curable and lower AIDS-related anxiety were independently associated with risky sex. No evidence of behavioral disinhibition was observed. Concerns regarding behavioral disinhibition should not slow down efforts to increase ART access in Africa.

Pediatric HIV Treatment Gaps in 7 East and Southern African Countries: Examination of Modeled, Survey, and Routine Program Data.

BACKGROUND: Remarkable success in the prevention and treatment of pediatric HIV infection has been achieved in the past decade. Large differences remain between the estimated number of children living with HIV (CLHIV) and those identified through national HIV programs. We evaluated the number of CLHIV and those on treatment in Lesotho, Malawi, Swaziland, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS: We assessed the total number of CLHIV, CLHIV on antiretroviral treatment (ART), and national and regional ART coverage gaps using 3 data sources: (1) Joint United Nations Programme on HIV/AIDS model-based estimates and national program data used as input values in the models, (2) population-based HIV impact surveys (PHIA), and (3) program data from the President's Emergency Plan for AIDS Relief (PEPFAR)-supported clinics. RESULTS: Across the 7 countries, HIV prevalence among children aged 0-14 years ranged from 0.4% (Uncertainty Bounds (UB) 0.2%-0.6%) to 2.8% (UB: 2.2%-3.4%) according to the PHIA surveys, resulting in estimates of 520,000 (UB: 460,000-580,000) CLHIV in 2016-2017 in the 7 countries. This compared with Spectrum estimates of pediatric HIV prevalence ranging from 0.5% (UB: 0.5%-0.6%) to 3.5% (UB: 3.0%-4.0%) representing 480,000 (UB: 390,000-550,000) CLHIV. CLHIV not on treatment according to the PEPFAR, PHIA, and Spectrum for the countries stood at 48% (UB: 25%-60%), 49% (UB: 37%-50%), and 38% (UB: 24%-47%), respectively. Of 78 regions examined across 7 countries, 33% of regions (PHIA data) or 41% of regions (PEPFAR data) had met the ART coverage target of 81%. CONCLUSIONS: There are substantial gaps in the coverage of HIV treatment in CLHIV in the 7 countries studied according to all sources. There is continued need to identify, engage, and treat infants and children. Important inconsistencies in estimates across the 3 sources warrant in-depth investigation.

Determining eligibility for antiretroviral therapy in resource-limited settings using total lymphocyte counts, hemoglobin and body mass index.

BACKGROUND: CD4+ T lymphocyte (CD4) cell count testing is the standard method for determining eligibility for antiretroviral therapy (ART), but is not widely available in sub-Saharan Africa. Total lymphocyte counts (TLCs) have not proven sufficiently accurate in identifying subjects with low CD4 counts. We developed clinical algorithms using TLCs, hemoglobin (Hb), and body mass index (BMI) to identify patients who require ART. METHODS: We conducted a cross-sectional study of HIV-infected adults in Uganda, who presented for assessment for ART-eligibility with WHO clinical stages I, II or III. Two by two tables were constructed to examine TLC thresholds, which maximized sensitivity for CD4 cell counts 350 cells microL. Hb and BMI values were then examined to try to improve model performance. RESULTS: 1787 subjects were available for analysis. Median CD4 cell counts and TLCs, were 239 cells/microL and 1830 cells/microL, respectively. Offering ART to all subjects with a TLCs 3000 cells/microL, and used Hb and/or BMI values to determine eligibility for those with TLC values between 2000 and 3000 cells/microL, marginally improved accuracy. CONCLUSION: TLCs appear useful in predicting who would be eligible for ART based on CD4 cell count criteria. Hb and BMI values may be useful in prioritizing patients for ART, but did not improve model accuracy.

Implementation and Operational Research: Strengthening HIV Test Access and Treatment Uptake Study (Project STATUS): A Randomized Trial of HIV Testing and Counseling Interventions.

OBJECTIVE: To determine which of 3 HIV testing and counseling (HTC) models in outpatient departments (OPDs) increases HIV testing and entry of newly identified HIV-infected patients into care. DESIGN: Randomized trial of HTC interventions. METHODS: Thirty-six OPDs in South Africa, Tanzania, and Uganda were randomly assigned to 3 different HTC models: (A) health care providers referred eligible patients (aged 18-49, not tested in the past year, not known HIV positive) to on-site voluntary counseling and testing for HTC offered and provided by voluntary counseling and testing counselors after clinical consultation; (B) health care providers offered and provided HTC to eligible patients during clinical consultation; and (C) nurse or lay counselors offered and provided HTC to eligible patients before clinical consultation. Data were collected from October 2011 to September 2012. We describe testing eligibility and acceptance, HIV prevalence, and referral and entry into care. Chi-square analyses were conducted to examine differences by model. RESULTS: Of 79,910 patients, 45% were age eligible and 16,099 (45%) age eligibles were tested. Ten percent tested HIV positive. Significant differences were found in percent tested by model. The proportion of age eligible patients tested by Project STATUS was highest for model C (54.1%, 95% confidence interval [CI]: 42.4 to 65.9), followed by model A (41.7%, 95% CI: 30.7 to 52.8), and then model B (33.9%, 95% CI: 25.7 to 42.1). Of the 1596 newly identified HIV positive patients, 94% were referred to care (96.1% in model A, 94.7% in model B, and 94.9% in model C), and 58% entered on-site care (74.4% in model A, 54.8% in model B, and 55.6% in model C) with no significant differences in referrals or care entry by model. CONCLUSIONS: Model C resulted in the highest proportion of all age-eligible patients receiving a test. Although 94% of STATUS patients with a positive test result were referred to care, only 58% entered care. We found no differences in patients entering care by HTC model. Routine HTC in OPDs is acceptable to patients and effective for identifying HIV-infected persons, but additional efforts are needed to increase entry to care.

The viral aetiology of influenza-like illnesses in Kampala and Entebbe, Uganda, 2008.

BACKGROUND: As the threat of zoonoses and the emergence of pandemic-prone respiratory viruses increases, there is a need to establish baseline information on the incidence of endemic pathogens in countries worldwide. OBJECTIVES: To investigate the presence of viruses associated with influenza-like illnesses (ILI) in Uganda. METHODS: A cross-sectional study was conducted in which nasopharyngeal swab specimens were collected from patients diagnosed with ILI in Kampala and Entebbe between 14 August 2008 - 15 December 2008. A multiplex polymerase chain reaction assay for detecting 12 respiratory viruses was used. RESULTS: A total of 369 patients (52.3% females) was enrolled; the median age was 6 years (range 1-70). One or more respiratory viruses were detected in 172 (46.6%) cases and their prevalence were influenza A virus (19.2%), adenovirus (8.7%), human rhinovirus A (7.9%), coronavirus OC43 (4.3%), parainfluenza virus 1 (2.7%), parainfluenza virus 3 (2.7%), influenza B virus (2.2%), respiratory syncytial virus B (2.2%), human metapneumovirus (1.4%), respiratory syncytial virus A (1.1%), parainfluenza virus 2 (0.5%) and coronavirus 229E (0.5%). There were 24 (14.0%) mixed infections. CONCLUSIONS: This study identified some of the respiratory viruses associated with ILI in Uganda. The circulation of some of the viruses was previously unknown in the study population. These results are useful in order to guide future surveillance and case management strategies involving respiratory illnesses in Uganda.

CD4+ T-cell count monitoring does not accurately identify HIV-infected adults with virologic failure receiving antiretroviral therapy.

BACKGROUND: CD4 T-lymphocyte (CD4) counts are widely used to monitor response to antiretroviral therapy (ART) in resource-limited settings. However, the utility of such monitoring in terms of predicting virologic response to therapy has been little studied. METHODS: We studied participants aged 18 years and older who initiated ART in Tororo, Uganda. CD4 counts, CD4 percentages, and viral load (VL) were examined at 6-monthly intervals. Various definitions of immunologic failure were examined to identify individuals with VLs>or=50, >or=500, >or=1000, or >or=5000 copies per milliliter at 6, 12, and 18 months after treatment initiation. RESULTS: One thousand sixty-three ART-naive persons initiated ART. The proportion of individuals with virologic failure ranged between 1.5% and 16.4% for each time point. The proportion with no increase in CD4 count from baseline did not differ between those with suppressed or unsuppressed VLs at 6, 18, and 24 months after ART initiation. No increase in CD4 cell counts at 6 months had a sensitivity of 0.04 [95% confidence interval (CI) 0.00 to 0.10] and a positive predictive value of 0.03 (95% CI 0.00 to 0.09) for identifying individuals with VL>or=500 copies per milliliter at 6 months. The best measure identified was an absolute CD4 cell count<125 cells per microliter at 21 months for predicting VL>or=500 copies per milliliter at 18 months which had a sensitivity of 0.13 (95% CI 0.01 to 0.21) and a positive predictive value of 0.29 (95% CI 0.10 to 0.44). CONCLUSIONS: CD4 cell count monitoring does not accurately identify individuals with virologic failure among patients taking ART.

Home-based antiretroviral care is associated with positive social outcomes in a prospective cohort in Uganda.

BACKGROUND: Home-based antiretroviral therapy (ART) care in Africa has expanded; but social outcomes of home-based ART programs are unknown. METHODS: Social experiences of participants in an antiretroviral therapy program involving weekly home visits in Uganda were assessed through interviews at enrollment and after 3 months and analyzed using generalized estimating equations. RESULTS: Of 654 participants, 72% were women; median baseline CD4 cell-count was 123 cells/muL. At follow-up, participants were more likely to report community support (adjusted odds ratio [OR] 2.10, 95% confidence interval [CI]: 1.46 to 3.03, P < 0.001), family support (OR 2.65, CI: 2.01 to 3.49, P < 0.001), and relationship strengthening (OR 2.10, CI: 1.46 to 3.03, P = 0.001) than at baseline; 84% attributed these experiences to antiretroviral therapy program participation. There was no change in incidence of negative experiences (P = 0.3). Forty-six percent of women reported a history of partner abuse, but abuse rates 3 months before and after program initiation were low (1% vs. 2%, OR 3.20, CI: 0.94 to 10.9, P = 0.063). Of five women who reported abuse associated with program participation, all had history of domestic violence. Of all participants reporting outcomes associated with antiretroviral therapy program participation at follow-up, 464 (79%) had only positive experiences, 35 (6%) had both positive and negative experiences, and <1% had only negative experiences. CONCLUSIONS: Participation in a home-based antiretroviral therapy program was associated with multiple positive social outcomes.

Performance of immunologic responses in predicting viral load suppression: implications for monitoring patients in resource-limited settings.

BACKGROUND: World Health Organization (WHO) guidelines for the use of antiretroviral therapy (ART) in resource-limited settings state that CD4 cell counts may be used to indicate when ART regimens should be changed because of treatment failure. The performance of immunologic monitoring for this purpose has not been evaluated, however. METHODS: Participants aged > or =18 years from the British Columbia HIV/AIDS Drug Treatment Program who had CD4 cell counts < or =200 cells/microL or an AIDS diagnosis at baseline had CD4 cell counts measured at 6 and 12 months after treatment initiation. Logistic regression analysis was used to calculate sensitivity, specificity, and positive and negative predictive values for immunologic responses in terms of predicting failure to achieve 2 viral load measurements < 500 copies/mL within 1 year. RESULTS: Viral load suppression occurred in 674 (60%) of 1125 subjects. Using no increase in CD4 cell counts at 6 months as a definition of treatment failure had a sensitivity of 34%, specificity of 94%, positive predictive value of 75%, and negative predictive value of 71% for predicting failure to achieve virologic suppression. Using 12-month CD4 cell count values, the measurements were 35%, 95%, 79%, and 73%, respectively. CONCLUSION: Immunologic criteria to predict which patients have not achieved virologic suppression results in significant misclassification of therapeutic responses.

Undiagnosed HIV infection and couple HIV discordance among household members of HIV-infected people receiving antiretroviral therapy in Uganda.

INTRODUCTION: Systematic efforts to identify HIV-infected members and HIV-discordant couples in households of individuals taking antiretroviral therapy (ART) could theoretically reduce HIV transmission and improve ART adherence. METHODS: We enrolled HIV-infected clients of an AIDS support organization in a randomized evaluation of different ART monitoring regimens that offered home-based ART care to them and their clinically eligible household members. At baseline, counselors visited participants' homes and offered voluntary counseling and testing (VCT) to all household members. We assessed uptake, HIV prevalence, HIV discordance, and rate of ART eligibility. RESULTS: Of the 2373 household members, 2348 (99%) accepted VCT. HIV prevalence among household members was 7.5% and varied by age with 9.5% among children aged 0 to 5 years, 2.9% among persons aged 6 to 24 years, and 37.1% among adults aged 25 to 44 years. Of the household members with HIV, 74% had never been previously tested, and 39% of these were clinically eligible for ART. Of the 120 spouses of ART patients that were tested for HIV, 52 (43%) were HIV negative, and of these, 99% had not been previously tested. CONCLUSIONS: Provision of home-based VCT to household members of people initiating ART was well accepted and resulted in the detection of a large number of previously undiagnosed HIV infections and HIV-discordant relationships.