Safety and Effectiveness of an All-Oral, Bedaquiline-Based, Shorter Treatment Regimen for Rifampicin-Resistant Tuberculosis in High Human Immunodeficiency Virus (HIV) Burden Rural South Africa: A Retrospective Cohort Analysis.

BACKGROUND: At the end of 2018, South Africa updated its all-oral regimen, to include bedaquiline (BDQ) and 2 months of linezolid (LZD) for all patients initiating the shorter 9-12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions. METHODS: We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between 1 July 2018 and 30 April 2019 in 3 facilities in King Cetshwayo District. An electronic register (EDR web) and facility-based clinical charts were used to collect variables, which were entered into an Epi-Info database. RESULTS: Our cohort included 117 patients; 68.4% (95% confidence interval [CI]: 59.3-76.3) tested positive for human immunodeficiency virus (HIV). The median time to culture conversion was 56 days (95% CI: 50-57). Treatment success was achieved in 75.2% (95% CI: 66.5-82.3) of patients. Mortality within the cohort was 12.8% (95% CI: 7.8-20.3). Anemia was the most frequent severe adverse event (AE). The median time to develop severe anemia was 7.1 weeks (interquartile range [IQR] 4.0-12.9) after treatment initiation. LZD was interrupted in 25.2% (95% CI: 17.8-34.5) of participants. CONCLUSIONS: An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. AEs are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to train staff in the monitoring, management, and reporting of AEs.

Correction: Increase in HIV viral suppression in KwaZulu-Natal, South Africa: Community-based cross sectional surveys 2018 and 2013. What remains to be done?

[This corrects the article DOI: 10.1371/journal.pone.0265488.].

Correction: Acceptability of unsupervised peer-based distribution of HIV oral self-testing for the hard-to-reach in rural KwaZulu Natal, South Africa: Results from a demonstration study.

[This corrects the article DOI: 10.1371/journal.pone.0264442.].

Changes Over Time in the Proportion of Advanced HIV Disease in Two High HIV Prevalence Settings in Ndhiwa (Kenya) and Eshowe (South Africa).

BACKGROUND: The burden of advanced HIV disease remains a significant concern in sub-Saharan Africa. In 2015, the World Health Organization released recommendations to treat all people living with HIV (PLHIV) regardless of CD4 ("treat all") and in 2017 guidelines for managing advanced HIV disease. We assessed changes over time in the proportion of PLHIV with advanced HIV and their care cascade in two community settings in sub-Saharan Africa. METHODS: Cross-sectional population-based surveys were conducted in Ndhiwa (Kenya) in 2012 and 2018 and in Eshowe (South Africa) in 2013 and 2018. We recruited individuals aged 15-59 years. Consenting participants were interviewed and tested for HIV at home. All participants with HIV had CD4 count measured. Advanced HIV was defined as CD4 < 200 cells/µL. RESULTS: Overall, 6076 and 6001 individuals were included in 2012 and 2018 (Ndhiwa) and 5646 and 3270 individuals in 2013 and 2018 (Eshowe), respectively. In Ndhiwa, the proportion of PLHIV with advanced HIV decreased from 2012 (159/1376 (11.8%; 95% CI: 9.8-14.2)) to 2018 (53/1000 (5.0%; 3.8-6.6)). The proportion of individuals with advanced HIV on antiretroviral therapy (ART) was 9.1% (6.9-11.8) in 2012 and 4.2% (3.0-5.8) in 2018. In Eshowe, the proportion with advanced HIV was 130/1400 (9.8%; 8.0-11.9) in 2013 and 38/834 (4.5%; 3.3-6.1) in 2018. The proportion with advanced HIV among those on ART was 6.9% (5.5-8.8) in 2013 and 2.8% (1.8-4.3) in 2018. There was a significant increase in coverage for all steps of the care cascade among people with advanced HIV between the two Ndhiwa surveys, with all the changes occurring among men and not women. No significant changes were observed in Eshowe between the surveys overall and by sex. CONCLUSION: The proportion with advanced HIV disease decreased between the first and second surveys where all guidelines have been implemented between the two HIV surveys.

Distribution of advanced HIV disease between two time periods in Ndhiwa (Kenya) and Eshowe (South Africa)We examined changes over time in the proportion of people living with HIV (PLHIV) with advanced HIV and their care cascade in two community settings in sub-Saharan Africa: Ndhiwa (Kenya) and Eshowe (South Africa). In 2012 and 2018, a total of 6,076 and 6,001 individuals were included in Ndhiwa, and 5,646 and 3,270 individuals were included in Eshowe in 2013 and 2018, respectively. In Ndhiwa, the proportion of PLHIV with advanced HIV decreased from 11.8% in 2012 to 5.0% in 2018. The proportion of individuals with advanced HIV on antiretroviral therapy (ART) decreased from 9.1% in 2012 to 4.2% in 2018. In Eshowe, the proportion PLHIV with advanced HIV decreased from 9.8% in 2013 to 4.5% in 2018. Among those on ART, the proportion of PLHIV with advanced HIV decreased from 6.9% in 2013 to 2.8% in 2018. The results also showed a significant increase in coverage for all steps of the care cascade among people with advanced HIV in Ndhiwa in 2018 compared to 2012, with these changes observed only among men and not women. No significant changes were observed in Eshowe between the surveys, both overall and when comparing by sex.

Correction: Retention on ART and viral suppression among patients in alternative models of differentiated HIV service delivery in KwaZulu-Natal, South Africa.

[This corrects the article DOI: 10.1371/journal.pgph.0000336.].

Evidence of HIV incidence reduction in young women, but not in adolescent girls, in KwaZulu-Natal, South Africa.

Objectives: We estimated changes in the HIV incidence from 2013-2018 in Eshowe/Mbongolwane, KwaZulu-Natal, South Africa where Médecins Sans Frontières is engaged in providing HIV testing and care since 2011. Methods: Using data from two cross-sectional household-based surveys conducted in 2013 and 2018, with consenting participants aged 15-59 years, we applied the incidence estimation frameworks of Mahiane et al and Kassanjee et al. Results: In total, 5599 (62.4% women) and 3276 (65.9% women) individuals were included in 2013 and 2018, respectively. We found a mean incidence in women aged 20-29 years of 2.71 cases per 100 person-years (95% confidence interval [CI]: 1.23;4.19) in 2013 and 0.4 cases per 100 person-years (95% CI: 0.0;1.5) in 2018. The incidence in men aged 20-29 years was 1.91 cases per 100 person-years (95% CI: 0.87; 2.93) in 2013 and 0.53 cases per 100 person-years (95% CI: 0.0; 1.4) in 2018. The incidence decline among women aged 15-19 was -0.34 cases per 100 person-years (95% CI: -1.31;0.64). Conclusions: The lack of evidence of incidence decline among adolescent girls is noteworthy and disconcerting. Our findings suggest that large-scale surveys should seriously consider focusing their resources on the core group of women aged 15-19 years.

Experiences and perceptions of urine sampling for tuberculosis testing among HIV patients: a multisite qualitative descriptive study.

OBJECTIVES: Evidence on the acceptability of urine-based assays for tuberculosis (TB) diagnosis among patients remains limited. We sought to describe patients' experiences and perceptions of urine sampling for TB testing at point of care. SETTING: Study sites in Kenya, Uganda, Mozambique and South Africa. PARTICIPANTS: Adult ambulatory HIV patients enrolled in a TB diagnostic study were selected purposively. INTERVENTION: For this qualitative descriptive study, audiorecorded individual interviews conducted with consenting participants were translated, transcribed and analysed using content analysis. Ethical agreement was obtained from relevant ethical review committees. RESULTS: Fifty-eight participants were interviewed. Three domains were identified. Overall, participants described urine sampling as easy, rapid and painless, with the main challenge being lacking the urge. Urine was preferred to sputum sampling in terms of simplicity, comfort, stigma reduction, convenience and practicality. While perceptions regarding its trustworthiness for TB diagnosis differed, urine sampling was viewed as an additional mean to detect TB and beneficial for early diagnosis. Participants were willing to wait for several hours for same-day results to allay the emotional, physical and financial burden of having to return to collect results, and would rather not pay for the test. Facilitators of urine sampling included cleanliness and perceived privacy of sampling environments, comprehensive sampling instructions and test information, as well as supplies such as toilet paper and envelopes ensuring confort and privacy when producing and returning samples. Participants motivation for accepting urine-based TB testing stemmed from their perceived susceptibility to TB, the value they attributed to their health, especially when experiencing symptoms, and their positive interactions with the medical team. CONCLUSIONS: This study suggests that urine sampling is well accepted as a TB diagnostic method and provides insights on how to promote patients' uptake of urine-based testing and improve their sampling experiences. These results encourage the future broad use of urine-based assays at point of care.

Novel FujiLAM assay to detect tuberculosis in HIV-positive ambulatory patients in four African countries: a diagnostic accuracy study.

BACKGROUND: Development of rapid biomarker-based tests that can diagnose tuberculosis using non-sputum samples is a priority for tuberculosis control. We aimed to compare the diagnostic accuracy of the novel Fujifilm SILVAMP TB LAM (FujiLAM) assay with the WHO-recommended Alere Determine TB-LAM Ag test (AlereLAM) using urine samples from HIV-positive patients. METHODS: We did a diagnostic accuracy study at five outpatient public health facilities in Uganda, Kenya, Mozambique, and South Africa. Eligible patients were ambulatory HIV-positive individuals (aged ≥15 years) with symptoms of tuberculosis irrespective of their CD4 T-cell count (group 1), and asymptomatic patients with advanced HIV disease (CD4 count <200 cells per µL, or HIV clinical stage 3 or 4; group 2). All participants underwent clinical examination, chest x-ray, and blood sampling, and were requested to provide a fresh urine sample, and two sputum samples. FujiLAM and AlereLAM urine assays, Xpert MTB/RIF Ultra assay on sputum or urine, sputum culture for Mycobacterium tuberculosis, and CD4 count were systematically carried out for all patients. Sensitivity and specificity of FujiLAM and AlereLAM were evaluated against microbiological and composite reference standards. FINDINGS: Between Aug 24, 2020 and Sept 21, 2021, 1575 patients (823 [52·3%] women) were included in the study: 1031 patients in group 1 and 544 patients in group 2. Tuberculosis was microbiologically confirmed in 96 (9·4%) of 1022 patients in group 1 and 18 (3·3%) of 542 patients in group 2. Using the microbiological reference standard, FujiLAM sensitivity was 60% (95% CI 51-69) and AlereLAM sensitivity was 40% (31-49; p<0·001). Among patients with CD4 counts of less than 200 cells per µL, FujiLAM sensitivity was 69% (57-79) and AlereLAM sensitivity was 52% (40-64; p=0·0218). Among patients with CD4 counts of 200 cells per µL or higher, FujiLAM sensitivity was 47% (34-61) and AlereLAM sensitivity was 24% (14-38; p=0·0116). Using the microbiological reference standard, FujiLAM specificity was 87% (95% CI 85-89) and AlereLAM specificity was 86% (95 CI 84-88; p=0·941). FujiLAM sensitivity varied by lot number from 48% (34-62) to 76% (57-89) and specificity from 77% (72-81) to 98% (93-99). INTERPRETATION: Next-generation, higher sensitivity urine-lipoarabinomannan assays are potentially promising tests that allow rapid tuberculosis diagnosis at the point of care for HIV-positive patients. However, the variability in accuracy between FujiLAM lot numbers needs to be addressed before clinical use. FUNDING: ANRS and Médecins Sans Frontières.

Increase in HIV viral suppression in KwaZulu-Natal, South Africa: Community-based cross sectional surveys 2018 and 2013. What remains to be done?

INTRODUCTION: High coverage of antiretroviral therapy (ART) in people living with HIV (PLHIV) increases viral suppression at population level and may reduce incidence. Médecins sans Frontières, in collaboration with the South African Department of Health, has been working in Eshowe/Mbongolwane (KwaZulu Natal) since 2011 to increase access to quality HIV services. Five years after an initial survey, we conducted a second survey to measure progress in HIV diagnosis and viral suppression and to identify remaining gaps. METHODS: A cross-sectional, population-based, stratified two-stage cluster survey was implemented in 2018, using the same design as in 2013. Consenting participants aged 15-59 years were interviewed and tested for HIV at home. Those HIV-positive were tested for HIV viral load (viral suppression defined as <1000 copies/mL). RESULTS: Overall, 3,278 individuals were included. The proportion of HIV-positive participants virally suppressed was 83.8% in 2018 compared to 57.1% in 2013 (p<0.001), with increases in all subpopulations. The largest gap remained in men aged 15-29 years, among whom viral suppression was 51.5%. Nevertheless, of the total unsuppressed participants, 60.3% were women, and 57.4% were individuals aged 30-59 years. Between 2013 and 2018, HIV-positive status awareness progressed from 75.2% to 89.9% and ART coverage among those aware from 70.4% to 93.8%, respectively. Among those on ART, 94.5% were virally suppressed in 2018. CONCLUSIONS: Viral suppression improved significantly from 2013 to 2018, in all age and gender groups of PLHIV. However, almost half of HIV-positive young men remained unsuppressed, while the majority of virally unsuppressed PLHIV were women and older adults. To continue lowering HIV transmission, specific strategies are needed to increase viral suppression in those groups.

Acceptability of unsupervised peer-based distribution of HIV oral self-testing for the hard-to-reach in rural KwaZulu Natal, South Africa: Results from a demonstration study.

BACKGROUND: Innovative models to distribute oral HIV self-tests (HIVST) provide an opportunity to increase access to HIV testing, especially for hard-to-reach populations. This study aimed to describe the acceptability of unsupervised peer-distribution of HIVST as a method to scale-up HIV testing. METHODS: In this study, lay counsellors or community health workers provided HIVST kits to primary recipients (PRs) for distribution to their sexual partners, anyone in their social network (termed secondary recipients) or for self-testing, from September 2018 to March 2020. The study was conducted in Eshowe and Mbongolwane areas in KwaZulu-Natal, South Africa. A structured questionnaire was administered during the recruitment and passive follow-up, when people came for confirmatory HIV testing. Electronic records were retrospectively examined to determine initiation of antiretroviral treatment (ART) for all HIVST users and non-users. RESULTS: Among 36,708 people approached to be primary recipients, 9,891 (26.9%) accepted; 31,341 HIVST kits were distributed with a median of three (IQR: 2-4) per peer. PRs were predominately recruited at primary health clinics (PHCs). However, acceptability of HIVST was thrice as high at community-based testing sites compared to PHCs (64.5% vs. 21.0%; p<0.001). During the study period, 34,715 adults were tested for HIV at both PHCs and community-based testing sites; of these, 1,089 individuals reported HIVST use. Among HIVST users, 893 (82.0%) returned to the clinic for confirmatory testing after testing negative on HIVST; 196 (17.9%) were confirmed HIV positive following a positive HIVST. After excluding 36/196 (18.4%) participants for whom clinical records could not be found in electronic register and 25/160 (15.6%) who were already on ART before receiving HIVST, 129/135 (95.5%) initiated ART, whereas 2,362/2685 (88%) of HIV positive HIVST non-users-initiated ART. CONCLUSION: Unsupervised peer-distribution of HIVST was feasible and acceptable, with more than 25% accepting to be peer-distributors. Acceptability of HIVST was thrice as high in community sites compared to clinics.

Retention on ART and viral suppression among patients in alternative models of differentiated HIV service delivery in KwaZulu-Natal, South Africa.

Differentiated models of HIV care (DMOC) aim to improve health care efficiency. We describe outcomes of five DMOC in KwaZulu-Natal, South Africa: facility adherence clubs (facility AC) and community adherence clubs (community AC), community antiretroviral treatment (ART) groups (CAG), spaced fast lane appointments (SFLA), and community pick up points (PuP). This retrospective cohort study included 8241 eligible patients enrolled into DMOC between 1/1/2012 and 31/12/2018. We assessed retention in DMOC and on ART, and viral load suppression (<1000 copies/mL). Kaplan-Meier techniques were applied to describe crude retention. Mixed effects parametric survival models with Weibull distribution and clustering on health center and individual levels were used to assess predictors for ART and DMOC attrition, and VL rebound (≥1000 copies/mL). Overall DMOC retention was 85%, 80%, and 76% at 12, 24 and 36 months. ART retention at 12, 24 and 36 months was 96%, 93%, 90%. Overall incidence rate of VL rebound was 1.9 episodes per 100 person-years. VL rebound rate was 4.9 episodes per 100 person-years among those enrolled in 2012-2015, and 0.8 episodes per 100 person-years among those enrolled in 2016-2018 (RR 0.12; 95% CI, 0.09-0.15, p<0.001). Prevalence of confirmed virological failure was 0.6% (38/6113). Predictors of attrition from DMOC and from ART were male gender, younger age, shorter duration on ART before enrollment. Low level viremia (>200-399 copies/mL) was associated with higher hazards of VL rebound and attrition from ART. Concurrent implementation of several DMOC in a large ART program is feasible and can achieve sustained retention on ART and VL suppression.

Feasibility and acceptability of using the novel urine-based FujiLAM test to detect tuberculosis: A multi-country mixed-methods study.

Background: The novel urine-based FujiLAM test identifies tuberculosis in HIV-positive patients but may be challenging to use at point-of-care (POC). Objectives: We assessed the feasibility and acceptability of using the FujiLAM test at point of care in outpatient settings. Methods: We conducted a mixed methods study in four outpatient settings in Kenya, Mozambique, South Africa, and Uganda between November 2020 and September 2021. The test was performed at POC in existing clinic laboratories and consultation spaces. We performed direct observations in the four health facilities, individual questionnaires, proficiency testing evaluations, and individual interviews among healthcare workers performing the FujiLAM test (healthcare workers), and group discussions with programme managers. Results: Overall, 18/19 (95%) healthcare workers and 14/14 (100%) managers agreed to participate in the study. Most assessed healthcare workers, including lay health workers (10/11; 91%), met the minimum required theoretical knowledge and practical skill in performing the FujiLAM test. Most healthcare workers (17/18; 94%) found the FujiLAM test overall "Easy/Very easy" to perform. Some challenges were mentioned: many timed steps (5/18; 28%); ensuring correct incubation period (5/18; 28%); test result readability (4/18; 22%); and difficulties with cartridge buttons (3/18; 17%). Half of the healthcare workers regularly performing the test (4/7; 57%) found it "Easy" to integrate into routine activities. Most healthcare workers and managers believed that any healthcare worker could perform the test after adequate training. Conclusions: Implementing the FujiLAM test in outpatient POC settings is feasible and acceptable to healthcare workers and managers. This test can be performed in various clinic locations by any healthcare worker. The timed, multi-step test procedure is challenging and may affect the workload in resource-constrained health facilities.

"We are part of a family". Benefits and limitations of community ART groups (CAGs) in Thyolo, Malawi: a qualitative study.

INTRODUCTION: In 2012 Community ART Groups (CAGs), a community-based model of antiretroviral therapy (ART) delivery were piloted in Thyolo District, Malawi as a way to overcome patient barriers to accessing treatment, and to decrease healthcare workers' workload. CAGs are self-formed groups of patients on ART taking turns to collect ART refills for all group members from the health facility. We conducted a qualitative study to assess the benefits and challenges of CAGs from patients' and healthcare workers' (HCWs) perspectives. METHODS: Data were collected by means of 15 focus group discussions, 15 individual in-depth interviews, and participant observation in 2 health centres. The 94 study participants included CAG members, ART patients eligible for CAGs who remained in conventional care, former CAG members who returned to conventional care and HCWs responsible for providing HIV care. Patient participants were purposively selected from ART registers, taking into account age and gender. Narratives were audio-recorded, transcribed, and translated from Chichewa to English. Data were analyzed through a thematic analysis. RESULTS: Patients and HCWs spoke favourably about the practical benefits of CAGs. Patient benefits included a reduced frequency of clinic visits, resulting in reduced transportation costs and time savings. HCW benefits included a reduced workload. Additionally peer support was perceived as an added value of the groups allowing not only sharing of the logistical constraints of drugs refills, but also enhanced emotional support. Identified barriers to joining a CAG included a lack of information on CAGs, unwillingness to disclose one's HIV status, change of residence and conflicts among CAG members. Participants reported that HIV-related stigma persists and CAGs were seen as an effective strategy to reduce exposure to discriminatory labelling by community members. CONCLUSION: In this setting, patients and HCWs perceived CAGs to be an acceptable model of ART delivery. Despite addressing important practical barriers to accessing ART, and providing peer support, CAGs were not well known by patients and had a limited impact on reducing HIV-related stigma. The CAG model of ART delivery should be considered in similar settings. Further measures need to be devised and implemented to address HIV-related stigma.