Tuberculosis prevalence after 4 years of population-wide systematic TB symptom screening and universal testing and treatment for HIV in the HPTN 071 (PopART) community-randomised trial in Zambia and South Africa: A cross-sectional survey (TREATS).

BACKGROUND: Tuberculosis (TB) prevalence remains persistently high in many settings, with new or expanded interventions required to achieve substantial reductions. The HIV Prevention Trials Network (HPTN) 071 (PopART) community-randomised trial randomised 14 communities to receive the "PopART" intervention during 2014 to 2017 (7 arm A and 7 arm B communities) and 7 communities to receive standard-of-care (arm C). The intervention was delivered door-to-door by community HIV care providers (CHiPs) and included universal HIV testing, facilitated linkage to HIV care at government health clinics, and systematic TB symptom screening. The Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening (TREATS) study aimed to measure the impact of delivering the PopART intervention on TB outcomes, in communities with high HIV and TB prevalence. METHODS AND FINDINGS: The study population of the HPTN 071 (PopART) trial included individuals aged ≥15 years living in 21 urban and peri-urban communities in Zambia and South Africa, with a total population of approximately 1 million and an adult HIV prevalence of around 15% at the time of the trial. Two sputum samples for TB testing were provided to CHiPs by individuals who reported ≥1 TB suggestive symptom (a cough for ≥2 weeks, unintentional weight loss ≥1.5 kg in the last month, or current night sweats) or that a household member was currently on TB treatment. Antiretroviral therapy (ART) was offered universally at clinics in arm A and according to local guidelines in arms B and C. The TREATS study was conducted in the same 21 communities as the HPTN 071 (PopART) trial between 2017 and 2022, and TB prevalence was a co-primary endpoint of the TREATS study. The primary comparison was between the PopART intervention (arms A and B combined) and the standard-of-care (arm C). During 2019 to 2021, a TB prevalence survey was conducted among randomly selected individuals aged ≥15 years (approximately 1,750 per community in arms A and B, approximately 3,500 in arm C). Participants were screened on TB symptoms and chest X-ray, with diagnostic testing using Xpert-Ultra followed by culture for individuals who screened positive. Sputum eligibility was determined by the presence of a cough for ≥2 weeks, or ≥2 of 5 "TB suggestive" symptoms (cough, weight loss for ≥4 weeks, night sweats, chest pain, and fever for ≥2 weeks), or chest X-ray CAD4TBv5 score ≥50, or no available X-ray results. TB prevalence was compared between trial arms using standard methods for cluster-randomised trials, with adjustment for age, sex, and HIV status, and multiple imputation was used for missing data on prevalent TB. Among 83,092 individuals who were eligible for the survey, 49,556 (59.6%) participated, 8,083 (16.3%) screened positive, 90.8% (7,336/8,083) provided 2 sputum samples for Xpert-Ultra testing, and 308 (4.2%) required culture confirmation. Overall, estimated TB prevalence was 0.92% (457/49,556). The geometric means of 7 community-level prevalence estimates were 0.91%, 0.70%, and 0.69% in arms A, B, and C, respectively, with no evidence of a difference comparing arms A and B combined with arm C (adjusted prevalence ratio 1.14, 95% confidence interval, CI [0.67, 1.95], p = 0.60). TB prevalence was higher among people living with HIV than HIV-negative individuals, with an age-sex-community adjusted odds ratio of 2.29 [95% CI 1.54, 3.41] in Zambian communities and 1.61 [95% CI 1.13, 2.30] in South African communities. The primary limitations are that the study was powered to detect only large reductions in TB prevalence in the intervention arm compared with standard-of-care, and the between-community variation in TB prevalence was larger than anticipated. CONCLUSIONS: There was no evidence that the PopART intervention reduced TB prevalence. Systematic screening for TB that is based on symptom screening alone may not be sufficient to achieve a large reduction in TB prevalence over a period of several years. Including chest X-ray screening alongside TB symptom screening could substantially increase the sensitivity of systematic screening for TB. TRIAL REGISTRATION: The TREATS study was registered with ClinicalTrials.gov Identifier: NCT03739736 on November 14, 2018. The HPTN 071 (PopART) trial was registered at ClinicalTrials.gov under number NCT01900977 on July 17, 2013.

Insaka: mobile phone support groups for adolescent pregnant women living with HIV.

BACKGROUND: Mobile phone-based interventions have been demonstrated in different settings to overcome barriers to accessing critical psychosocial support. In this study, we aimed to assess the acceptability and feasibility of a phone-based, peer-to-peer support group intervention for adolescent pregnant women aged 15-24 years living with HIV in Zambia. METHODS: Sixty-one consenting participants were recruited from Antenatal Clinics of two large urban communities in Lusaka. They were invited to participate in the mobile phone-based intervention that allowed them to anonymously communicate in a small group led by a facilitator for 4 months. A mixed methods approach was used to assess acceptability and feasibility, including a focus group discussion, pre- and post-intervention interview and analysis of the content of the text message data generated. RESULTS: Participants reported finding the platform "not hard to use" and enjoyed the anonymity of the groups. Seventy-one percent of participants (n = 43) participated in the groups, meaning they sent text messages to their groups. Approximately 12,000 text messages were sent by participants (an average of 169 messages/user and 6 mentors in 6 groups. Topics discussed were related to social support and relationships, stigma, HIV knowledge and medication adherence. CONCLUSION: The study showed that the intervention was acceptable and feasible, and highlighted the potential of the model for overcoming existing barriers to provision of psychosocial support to this population.

Evaluation of COVID-19 antigen rapid diagnostic tests for self-testing in Lesotho and Zambia.

INTRODUCTION: The use of antigen rapid tests (Ag-RDTs) for self-testing is an important element of the COVID-19 control strategy and has been widely supported. However, scale-up of self-testing for COVID-19 in sub-Saharan Africa is still insufficient and there is limited evidence on the acceptability of self-testing and agreement between Ag-RDT self-testing and Ag-RDT testing by professional users. A joint collaboration (Botnar Research Centre for Child Health-European & Developing countries Clinical Trials Partnership)was established between Lesotho and Zambia to address these gaps in relation to Ag-RDT self-testing and contribute to increasing its use in the region. METHODS: A cross-sectional study was conducted with qualitative and quantitative data analysis. Firstly, 14 in-depth cognitive interviews (5 in Zambia and 9 in Lesotho) were performed to assess the participants' understanding of the instructions for use (IFU) for self-testing. In a second step, evaluation of test agreement between Ag-RDT self-testing and Ag-RDT testing by professional user using SD Biosensor STANDARD Q COVID-19 Ag-RDT was performed. In Zambia, usability and acceptability of self-testing were also assessed. RESULTS: Cognitive interviews in Lesotho and Zambia showed overall good understanding of IFU. In Zambia, acceptability of self-testing was high, though some participants had difficulties in conducting certain steps in the IFU correctly. Agreement between Ag-RDT self-test and Ag-RDT by professional users in Lesotho (428 participants) and Zambia (1136 participants) was high, 97.3% (403/414, 95% CI: 95.3-98.7) and 99.8% (1116/1118, 95% CI: 99.4-100) respectively. CONCLUSION: Findings from this study support the use of Ag-RDT self-testing within COVID-19 control strategies in sub-Saharan Africa, contributing to increase the testing capacity and access in hard-to reach settings.

Use of point-of-care C-reactive protein testing for screening of tuberculosis in the community in high-burden settings: a prospective, cross-sectional study in Zambia and South Africa.

BACKGROUND: WHO recommends community-wide, systematic tuberculosis screening in high-prevalence settings. C-reactive protein has been proposed as a tuberculosis screening tool for people living with HIV. We aimed to assess the performance of a point-of-care C-reactive protein test for tuberculosis screening in the community in two countries with a high tuberculosis burden. METHODS: We conducted a prospective, cross-sectional study in four communities in Zambia and South Africa, nested in a tuberculosis prevalence survey. We included adults (aged ≥15 years) who were sputum-eligible (tuberculosis-suggestive symptoms or computer-aided-detection score ≥40 on chest x-ray) and whose sputum was tested with Xpert Ultra and liquid culture. A 5% random sample of individuals who were non-sputum-eligible was also included. We calculated sensitivity and specificity of point-of-care C-reactive protein testing, alone and combined with symptom screening, to detect tuberculosis in participants who were sputum-eligible, compared with a microbiological reference standard (positive result in Xpert Ultra, culture, or both). FINDINGS: Between Feb 19 and Aug 11, 2019, 9588 participants were enrolled in the tuberculosis prevalence study, 1588 of whom had C-reactive protein testing and received results (875 [55·1%] were women and girls, 713 [44·9%] were men and boys, 1317 [82·9%] were sputum-eligible, and 271 [17·1%] were non-sputum-eligible). Among participants who were sputum-eligible, we identified 76 individuals with tuberculosis, of whom 25 were living with HIV. Sensitivity of point-of-care C-reactive protein testing with a cutoff point of 5 mg/L or more was 50·0% (38/76, 95% CI 38·3-61·7) and specificity was 72·3% (890/1231, 69·7-74·8). Point-of-care C-reactive protein combined in parallel with symptom screening had higher sensitivity than symptom screening alone (60·5% [46/76, 95% CI 48·6-71·6] vs 34·2% [26/76, 23·7-46·0]). Specificity of point-of-care C-reactive protein combined in parallel with symptom screening was 51·7% (636/1231, 95% CI 48·8-54·5) versus 70·5% (868/1231, 67·9-73·0) with symptom screening alone. Similarly, in people living with HIV, sensitivity of point-of-care C-reactive protein combined with symptom screening was 72·0% (18/25, 95% CI 50·6-87·9) and that of symptom screening alone was 36·0% (9/25, 18·0-57·5). Specificity of point-of-care C-reactive protein testing combined in parallel with symptom screening in people living with HIV was 47·0% (118/251, 95% CI 40·7-53·4) versus 72·1% (181/251, 66·1-77·6) with symptom screening alone. INTERPRETATION: Point-of-care C-reactive protein testing alone does not meet the 90% sensitivity stipulated by WHO's target product profile for desirable characteristics for screening tests for detecting tuberculosis. However, combined with symptom screening, it might improve identification of individuals with tuberculosis in communities with high prevalence, and might be particularly useful where other recommended tools, such as chest x-ray, might not be readily available. FUNDING: European and Developing Countries Clinical Trials Partnership.

Depressive symptoms and HIV risk behaviours among adolescents enrolled in the HPTN071 (PopART) trial in Zambia and South Africa.

BACKGROUND: Mental health is a critical and neglected public health problem for adolescents in sub-Saharan Africa. In this paper we aim to determine the prevalence of depressive symptoms and the association with HIV risk behaviours in adolescents aged 15-19 years in Zambia and SA. METHODS: We conducted a cross-sectional survey from August-November 2017 in seven control communities of HPTN 071 (PopART) trial (a community-randomised trial of universal HIV testing and treatment), enrolling approximately 1400 eligible adolescents. HIV-status was self-reported. Depressive symptoms were measured with the Short Mood and Feelings Questionnaire (SMFQ), with a positive screen if adolescents scored ≥12. We fitted a logistic regression model to identify correlates of depressive symptoms with subgroup analyses among those who self-reported ever having had sex, by gender and country. RESULTS: Out of 6997 households approached, 6057 (86.6%) were enumerated. 2546 adolescents were enumerated of whom 2120 (83.3%) consented to participate and were administered the SMFQ. The prevalence of depressive symptoms was 584/2120 (27.6%) [95%CI: 25.7%-29.5%]. Adolescents in SA were less likely to experience depressive symptoms (Adjusted Odds Ratio [AOR] = 0.63 (95% CI: 0.50, 0.79), p-value<0.0001). Female adolescents (AOR = 1.46 (95% CI: 1.19, 1.81), p-value<0.0001); those who reported ever having sex and being forced into sex (AOR = 1.80 (95% CI: 1.45, 2.23), p-value<0.001) and AOR = 1.67 (95% CI: 0.99, 2.84); p-value = 0.057 respectively) were more likely to experience depressive symptoms. Among 850 (40.1%) adolescents who self-reported to ever having had sex; those who used alcohol/drugs during their last sexual encounter were more likely to experience depressive symptoms (AOR = 2.18 (95% CI: 1.37, 3.47); p-value = 0.001), whereas those who reported using a condom were less likely to experience depressive symptoms (AOR = 0.74 (95% CI: 0.55, 1.00); p-value = 0.053). CONCLUSION: The prevalence of depressive symptoms among adolescents ranged from 25-30% and was associated with increased HIV-risk behaviour.

Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South Africa.

OBJECTIVES: Prevalence surveys remain the best way to assess the national tuberculosis (TB) burden in many countries. Challenges with using culture (the reference standard) for TB diagnosis in prevalence surveys have led to increasing use of molecular tests (Xpert assays), but discordance between these two tests has created problems for deciding which individuals have TB. We aimed to design an accurate diagnostic algorithm for TB prevalence surveys (TBPS) that limits the use of culture. DESIGN: TBPS in four communities, conducted during 2019. SETTING: Three Zambian communities and one South-African community included in the TBPS of the Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening study. PARTICIPANTS: Randomly sampled individuals aged ≥15 years. Among those who screened positive on chest X-ray or symptoms, two sputum samples were collected for field Xpert-Ultra testing and a third for laboratory liquid-culture testing. Clinicians reviewed screening and test results; in Zambia, participants with Mycobacterium tuberculosis-positive results were followed up 6-13 months later. Among 10 984 participants, 2092 screened positive, 1852 provided two samples for Xpert-Ultra testing, and 1009 had valid culture results. OUTCOMES: Culture and Xpert-Ultra test results. RESULTS: Among 946 culture-negative individuals, 917 were Xpert-negative, 12 Xpert-trace-positive and 17 Xpert-positive (grade very low, low, medium or high), with Xpert categorised as the highest grade of the two sample results. Among 63 culture-positive individuals, 8 were Xpert-negative, 9 Xpert-trace-positive and 46 Xpert-positive. Counting trace-positive results as positive, the sensitivity of Xpert-Ultra compared with culture was 87% (95% CI 76% to 94%) using two samples compared with 76% (95% CI 64% to 86%) using one. Specificity was 97% when trace-positive results were counted as positive and 98% when trace-positive results were counted as negative. Most Xpert-Ultra-positive/culture-negative discordance was among individuals whose Xpert-positive results were trace-positive or very low grade or they reported previous TB treatment. Among individuals with both Xpert-Ultra results grade low or above, the positive-predictive-value was 90% (27/30); 3/30 were plausibly false-negative culture results. CONCLUSION: Using Xpert-Ultra as the primary diagnostic test in TBPS, with culture only for confirmatory testing, would identify a high proportion of TB cases while massively reducing survey culture requirements. TRIAL REGISTRATION NUMBER: NCT03739736.