Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV: a diagnostic accuracy study.

BackgroundSymptom-based screening for tuberculosis is recommended for all people living with HIV. This recommendation results in unnecessary Xpert MTB/RIF testing in many individuals living in tuberculosis-endemic areas and thus poor implementation of intensified case finding and tuberculosis preventive therapy. Novel approaches to tuberculosis screening are needed to help achieve global targets for tuberculosis elimination. We assessed the performance of C-reactive protein (CRP) measured with a point-of-care assay as a screening tool for active pulmonary tuberculosis.MethodsFor this prospective study, we enrolled adults (aged ≥18 years) living with HIV with CD4 cell count less than or equal to 350 cells per μL who were initiating antiretroviral therapy (ART) from two HIV/AIDS clinics in Uganda. CRP concentrations were measured at study entry with a point-of-care assay using whole blood obtained by fingerprick (concentration ≥10 mg/L defined as screen positive for tuberculosis). Sputum samples were collected for Xpert MTB/RIF testing and culture. We calculated the sensitivity and specificity of point-of-care CRP and WHO symptom-based screening in reference to culture results. We repeated the sensitivity analysis with Xpert MTB/RIF as the reference standard.FindingsBetween July 8, 2013, and Dec 15, 2015, 1237 HIV-infected adults were enrolled and underwent point-of-care CRP testing. 60 (5%) patients with incomplete or contaminated cultures were excluded from the analysis. Of the remaining 1177 patients (median CD4 count 165 cells per μL [IQR 75-271]), 163 (14%) had culture-confirmed tuberculosis. Point-of-care CRP testing had 89% sensitivity (145 of 163, 95% CI 83-93) and 72% specificity (731 of 1014, 95% CI 69-75) for culture-confirmed tuberculosis. Compared with WHO symptom-based screening, point-of-care CRP testing had lower sensitivity (difference -7%, 95% CI -12 to -2; p=0·002) but substantially higher specificity (difference 58%, 95% CI 55 to 61; p<0·0001). When Xpert MTB/RIF results were used as the reference standard, sensitivity of point-of-care CRP and WHO symptom-based screening were similar (94% [79 of 84] vs 99% [83 of 84], respectively; difference -5%, 95% CI -12 to 2; p=0·10).InterpretationThe performance characteristics of CRP support its use as a tuberculosis screening test for people living with HIV with CD4 count less than or equal to 350 cells per μL who are initiating ART. HIV/AIDS programmes should consider point-of-care CRP-based tuberculosis screening to improve the efficiency of intensified case finding and increase uptake of tuberculosis preventive therapy.FundingNational Institutes of Health; President's Emergency Plan for AIDS Relief; University of California, San Francisco, Nina Ireland Program for Lung Health

Clinical characteristics and morbidity among hospitalized adults with advanced HIV disease in Uganda during 'test and treat' era.

Nearly four decades after the first case of AIDS was described, the global number of AIDS-related deaths has steadily declined but falls short of the elimination targets, especially in sub-Saharan Africa. Despite interventions to promote early HIV diagnosis and treatment, hospitalization and mortality related to advanced HIV disease (AHD) remains a significant public health problem in Uganda. We assessed the HIV treatment history and causes of hospitalization among in-patients with AHD at a tertiary hospital in Uganda. In this cross-sectional study, pre-hospitalization HIV treatment history and clinical characteristics of HIV-positive in-patients with CD4<200 cells/μL or WHO stage 3 or 4 clinical events were assessed. Descriptive data were summarized using percentages and medians. Among hospitalized adults with AHD from November 2021 to June 2022, 74% (260/353) knew their HIV status prior to hospitalization and 62% (219/353) were ART experienced at presentation. The median time since ART initiation was 28 months (IQR; 2-97). Overall, 73% (258/353) had at least two etiological diagnoses and the majority (non-mutually exclusive) were diagnosed with tuberculosis (61.2%), cryptococcal meningitis (20.7%), mucosal candidiasis (16.1%) and bacterial infections (15%). In conclusion, nearly two-thirds of in-patients with advanced HIV disease were ART experienced prior to hospitalization and tuberculosis was the most common cause of hospitalization. Innovative strategies to strengthen HIV diagnosis, linkage, and retention in HIV care and to increase coverage of TB preventive therapy are urgently needed

HIV viral load suppression among people with mental disorders at two urban HIV clinics in Uganda: a parallel convergent mixed methods study using the social ecological model

Abstract Background Uganda adopted and implemented the Universal Test and Treat (UTT) guidelines in 2017, which require HIV-infected persons to be initiated on antiretroviral therapy (ART) at any CD4 + cell count, and to be routinely monitored for viral load to assess response to ART. However, there is paucity of data on viral load suppression (VLS) among people living with HIV (PLHIV) with mental disorders. We conducted a parallel convergent mixed methods study to determine HIV VLS among people with a mental disorder and explored the socio-cultural determinants of VLS at Butabika hospital and Mulago (ISS) HIV Clinics in Uganda. Methods We conducted a retrospective medical records review; seven key informant interviews (KII) among purposively selected healthcare providers and 12 in-depth interviews (IDI) among clinically stable PLHIV with a mental disorder. Data was collected on demographics, mental disorder, ART, viral load status, social support, stigma, and disclosure of HIV status. Quantitative data was analysed using descriptive statistics and modified Poisson regression, while Inductive thematic analysis was used for the qualitative data. Results Of the 240 PLHIV with a mental disorder who were enrolled, 161 (67.1%) were female with mean age 38.9 (± 11.2) years. Overall, 88.8% (95% Cl: 84.0 – 92.2%) achieved VLS. Age (aPR = 1.00, 95%Cl = 1.00–1.00), male gender (aPR = 0.90, 95%Cl = 0.82–0.98), divorced (aPR = 0.88, 95%Cl = 0.82–0.94), widowed (aPR = 0.84, 95%Cl = 0.83–0.86), baseline CD4 count < 200 (aPR = 0.89, 95%Cl = 0.85–0.94), psychotic mental disorders (aPR = 1.11; 95%CI = 1.08–1.13) and fair (85–94%) ART adherence level (aPR = 0.69, 95%Cl = 0.55–0.87) and TDF/3TC/DTG (aPR = 0.92; 95%CI = 0.91–0.94) were associated with HIV VLS. Social support from family members, knowledge of impact of negative thoughts on VLS, fear of breaking up with partners and compassionate healthcare providers positively influenced VLS. Stigma and discrimination from the community, self-perceived stigma hindering social relations, socio-economic challenges and psychiatric drug stock-outs negatively affected VLS. Conclusion and recommendations HIV VLS among PLHIV with mental disorders at institutions that provide integrated HIV and mental health care is still below the UNAIDS 95% target. Health promotion messaging focusing on benefits of VLS and countering stigma to create a safe environment; and active involvement of family members in care could improve HIV treatment outcomes for PLHIV with mental disorders

Impact of hematocrit on point-of-care C-reactive protein-based tuberculosis screening among people living with HIV initiating antiretroviral therapy in Uganda

Point-of-care C-reactive protein (POC CRP) testing is a potential tuberculosis (TB) screening tool for people living with HIV (PLHIV). Unlike lab-based assays, POC assays do not routinely adjust CRP levels for hematocrit, potentially resulting in TB screening status misclassification. We compared the diagnostic accuracy of unadjusted and hematocrit-adjusted POC CRP for culture-confirmed TB among PLHIV with CD4 cell-count ≤350 cells/uL initiating antiretroviral therapy (ART) in Uganda. We prospectively enrolled consecutive adults, measured POC CRP (Boditech; normal &lt;8 mg/L), collected two spot sputum specimens for comprehensive TB testing, and extracted pre-ART hematocrit from clinic records. Of the 605 PLHIV included, hematocrit-adjusted POC CRP had similar sensitivity (80% vs 81%, difference +1% [95% CI -3 to +5], P= 0.56) and specificity (71% vs 71%, difference 0% [95% CI -1 to +1], P= 0.56) for culture-confirmed TB, relative to unadjusted POC CRP. When used for TB screening, POC CRP may not require adjustment for hematocrit. However, larger studies may be required if differences close to the clinically meaningful threshold are to be detected

Predictors of delayed Anti-Retroviral Therapy initiation among adults referred for HIV treatment in Uganda: a cross-sectional study

Abstract Background Uganda’s current guidelines recommend immediate initiation of Anti-Retroviral Therapy (ART) for persons living with HIV in order to reduce HIV/AIDS related morbidity and mortality. However, not all eligible PLHIV initiate ART within the recommended time following HIV diagnosis. We assessed the prevalence and factors associated with delayed ART initiation among PLHIV referred for ART initiation, five years since rolling out the test and treat guidelines. Methods In this cross-sectional study, we enrolled adult patients referred to Mulago Immune Suppressive Syndrome (Mulago ISS) clinic for ART initiation from January 2017 to May 2021. We collected data on socio-demographics, HIV diagnosis and referral circumstances, and time to ART initiation using a questionnaire. The outcome of interest was proportion of patients that delayed ART, defined as spending more than 30 days from HIV diagnosis to ART initiation. We performed multivariable logistic regression and identified significant factors. Results A total of 312 patients were enrolled of which 62.2% were female. The median (inter-quartile range [IQR]) age and baseline CD4 count of the patients were 35 (28–42) years and 315 (118.8–580.5) cells/μL respectively. Forty-eight (15.4%) patients delayed ART initiation and had a median (IQR) time to ART of 92 (49.0–273.5) days. The factors associated with delayed ART initiation were; 1) having had the HIV diagnosis made from a private health facility versus public, (adjusted odds ratio [aOR] = 2.4 (95% confidence interval [CI] 1.1–5.5); 2) initial denial of positive HIV test results, aOR = 5.4 (95% CI: 2.0–15.0); and, 3) having not received a follow up phone call from the place of HIV diagnosis, aOR = 2.8 (95% CI: 1.2–6.8). Conclusion There was significant delay of ART initiation among referred PLHIV within 5 years after the rollout of test and treat guidelines in Uganda. Health system challenges in the continuity of HIV care services negatively affects timely ART initiation among referred PLHIV in Uganda

Changes in the Timing of Antiretroviral Therapy Initiation in HIV-Infected Patients With Tuberculosis in Uganda: A Study of the Diffusion of Evidence Into Practice in the Global Response to HIV/AIDS

BackgroundWe aimed to determine the extent to which emerging evidence and changing guidelines regarding timing of antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected patients with tuberculosis influenced "real-world" clinical practice in Uganda.MethodsWe evaluated ART-naive, HIV-infected adults starting tuberculosis therapy at 2 HIV clinics in Uganda between 26 August 2006 and 29 September 2012. We used multivariate regression to calculate associations between 4 calendar periods reflecting publication of seminal clinical studies or changes in guidelines and timing of ART after tuberculosis therapy initiation.ResultsFor patients with CD4 counts &lt;50 cells/µL, the fraction starting ART within 14 and 30 days of initiating tuberculosis therapy increased from 7% to 14% and from 14% to 86% over the period of observation. The fraction of patients with CD4 counts &gt;50 cells/µL starting ART within 60 days increased from 16% to 28%. After adjustment for sociodemographic factors, when comparing the most recent with the earliest calendar period, the rate of ART initiation increased by 4.57-fold (95% confidence interval [CI], 1.76-fold to 11.86-fold) among patients with baseline CD4 counts ≤ 50 cells/µL and by 5.43-fold (95% CI, 3.16- fold to 9.31-fold) among those with baseline CD4 counts &gt;50 cells/µL.ConclusionsWe observed large changes in clinical practice during a period of emerging data and changing guidelines among HIV-infected patients with tuberculosis. Nonetheless, a significant proportion of individuals with higher CD4 cell counts do not start ART within recommended time frames. Targeted dissemination and implementation efforts are still needed to achieve target levels in practice