Retrospective cohort analysis of antiretroviral therapy initiation timelines and clinical outcomes in adults with HIV and TB disease in KwaZulu-Natal, South Africa.

BackgroundWe aimed to determine antiretroviral therapy (ART) initiation timing and outcomes in people living with HIV (PLHIV) receiving tuberculosis treatment in KwaZulu-Natal, South Africa.MethodsWe performed a retrospective cohort analysis of routinely collected de-identified data from 62 clinics including PLHIV not already receiving ART aged ≥16 years, starting tuberculosis treatment between October 2016-November 2019. Multivariable Poisson regression models with robust standard errors evaluated associations between timing of ART initiation (after starting tuberculosis treatment) and successful tuberculosis treatment, and 6-month HIV viral load (VL) < 50 copies/mL.

Safety and immunogenicity of investigational tuberculosis vaccine M72/AS01 in people living with HIV in South Africa: an observer-blinded, randomised, controlled, phase 2 trial.

Background: M72/AS01 is a recombinant fusion protein vaccine candidate derived from two Mycobacterium tuberculosis antigens (Mtb32A and Mtb39A) and AS01 adjuvant. We evaluated safety and immunogenicity of M72/AS01 in people living with HIV in South Africa.

Methods: In this observer-blinded, randomised, controlled, phase 2 trial, participants aged 16-35 years with well controlled HIV were enrolled from urban, semi-urban, and semi-rural settings in South Africa, including sites with high tuberculosis and HIV prevalence, as well as agricultural and mining communities.

Feasibility and acceptability of GeneXpert MTB/XDR implementation among healthcare workers in three low-middle income African countries.

Background: Xpert MTB/XDR (Xpert-XDR) testing can significantly shorten time to initiating appropriate drug-resistant tuberculosis (DR-TB) treatment, but its introduction may impact laboratory workflow, especially in laboratories not currently performing drug susceptibility testing. This study evaluated the feasibility and acceptability of implementing the Xpert-XDR for rapid triage and selection of all-oral regimens for DR-TB.

Method: This was a multi-country, multi-site qualitative study conducted between July and November 2023, as part of the larger TriAD (Triage test for All oral DR TB drugs) study implemented in South Africa, Ethiopia, and Nigeria.

BCG Revaccination for the Prevention of Infection.

Background: In a previous phase 2 trial, bacille Calmette-Guérin (BCG) revaccination was not shown to provide protection from primary infection but prevented sustained infection, defined by an initial conversion on a QuantiFERON-TB (QFT) test (an interferon- release assay) from negative to positive, followed by two additional positive QFT tests at 3 and 6 months after the initial conversion (a secondary end point). A vaccine efficacy of 45% (95% confidence interval [CI], 6 to 68) was observed.

Methods: We performed a phase 2b, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of BCG revaccination, as compared with placebo, for the prevention of sustained QFT test conversion (primary end point) in QFT test-negative, human immunodeficiency virus (HIV)-negative adolescents.

Impact of increasing CD4 count threshold eligibility for antiretroviral therapy initiation on advanced HIV disease and tuberculosis prevalence and incidence in South Africa: an interrupted time series analysis.

Introduction: We investigated the impact of increasing CD4 count eligibility for antiretroviral therapy (ART) initiation on advanced HIV disease (AHD) and tuberculosis (TB) prevalence and incidence among people living with HIV (PLHIV) in South Africa.

Methods: We conducted an interrupted time series analysis with de-identified data of PLHIV aged ≥15 years initiating ART between April 2012 and February 2020 at 65 primary healthcare clinics in KwaZulu-Natal, South Africa. Outcomes included monthly proportions of new ART initiators presenting with AHD (CD4 count <200 cells/µL) and TB disease.

High mortality among patients with tuberculosis accessing primary care facilities: secondary analysis from an open-label cluster-randomised trial.

Background: Tuberculosis (TB) mortality remains persistently high, despite global TB control efforts. The aim of this study was to assess if a quality improvement (QI) intervention reduced deaths in TB patients accessing primary healthcare (PHC) services.

Methods: In this pre specified secondary analysis of a cluster-randomized controlled study conducted in 2016-2018 in South Africa (Clinicaltrials.

IgG antibody response to Mycobacterium tuberculosis curli pili (MTP) in people from different geographical regions in Sub-Saharan Africa.

Previously, a slot blot or an indirect enzyme-linked immunosorbent assay (ELISA) using a synthetic or purified MTP antigen, conceptually demonstrated IgG antibody induction in pulmonary TB patients, albeit with small sample sizes and differing sensitivity. Therefore, we evaluated an IgG MTP ELISA in larger populations from The Gambia (n = 549), Uganda (n = 161), and South Africa (n = 193), comprising human immunodeficiency virus (HIV) positive and negative, with microbiologically confirmed active TB. The association between the IgG level and demographic characteristics was determined by multivariate logistic regression.

Pharmacokinetics and safety of dolutegravir in children receiving rifampicin tuberculosis treatment in South Africa (ORCHID): a prospective cohort study.

Background: Data on the safety and pharmacokinetics of dolutegravir in children with HIV and tuberculosis are scarce. We aimed to determine the pharmacokinetics and safety of dolutegravir 50 mg twice daily in children receiving rifampicin, and to predict exposures for once-daily dolutegravir with rifampicin.

Methods: ORCHID is an open-label, sequential, prospective cohort study in children (<18 years) weighing 20-35 kg initiated on a rifampicin-based tuberculosis regimen and dolutegravir in Durban, South Africa.

Triage test for all-oral drug-resistant tuberculosis (DR-TB) regimen: a phase IV study to assess effectiveness, feasibility, acceptability and cost-effectiveness of the Xpert MTB/XDR assay for rapid triage and treatment of DR-TB.

Introduction: The TriAD study will assess the Xpert MTB/XDR (Xpert XDR; Cepheid) assay to detect tuberculosis (TB) drug resistance in sputum testing positive for TB to rapidly triage and treat patients with a short all-oral treatment regimen.

Methods And Analysis: In this study, approximately 4800 Xpert MTB/RIF or Ultra MTB-positive patients (irrespective of rifampicin (RIF) resistance (RR) status) from several clinical sites across South Africa, Nigeria and Ethiopia will be enrolled over 18-24 months and followed-up for approximately 6 months post-TB treatment completion. Participants will be enrolled into one of two cohorts based on Xpert MTB/RIF and Xpert XDR results: () positive participants with RR in Cohort 1 (n=880) and positive RIF susceptible TB patients with isoniazid mono-resistance irrespective of presence of resistance to fluoroquinolones, second-line injectable drugs or ethionamide in Cohort 2 (n=400).

Patterns of HIV-1 Drug Resistance Observed Through Geospatial Analysis of Routine Diagnostic Testing in KwaZulu-Natal, South Africa.

HIV-1 drug resistance (HIVDR) impedes treatment and control of HIV-1, especially in high-prevalence settings such as KwaZulu-Natal (KZN) province, South Africa. This study merged routine HIV-1 genotypic resistance test (GRT) data with Geographic Information Systems coordinates to assess patterns and geographic distribution of HIVDR in KZN, among ART-experienced adults with virological failure. We curated 3133 GRT records generated between 1 January 2018 and 30 June 2022, which includes the early phase of dolutegravir (DTG) rollout, of which 2735 (87.

Evaluating diagnostic accuracy of an RT-PCR test for the detection of SARS-CoV-2 in saliva.

Background And Objective: Saliva has been proposed as a potential more convenient, cost-effective, and easier sample for diagnosing SARS-CoV-2 infections, but there is limited knowledge of the impact of saliva volumes and stages of infection on its sensitivity and specificity.

Methods: In this study, we assessed the performance of SARS-CoV-2 testing in 171 saliva samples from 52 mostly mildly symptomatic patients (aged 18 to 70 years) with a positive reference standard result at screening. The samples were collected at different volumes (50, 100, 300, and 500 µl of saliva) and at different stages of the disease (at enrollment, day 7, 14, and 28 post SARS-CoV-2 diagnosis).

The impact of COVID-19 national lockdowns on drug-resistant tuberculosis in KwaZulu-Natal, South Africa: A spatial analysis.

Purpose: We sought to understand the impact of the initial COVID-19 mitigation strategies in 2020 on drug-resistant (DR) TB diagnoses in KwaZulu-Natal province (KZN), South Africa.

Methods: We compared the number, spatial distribution, and characteristics of DR TB diagnoses before and after the initial COVID-19 lockdown on March 26th, 2020. Information on DR TB diagnoses was collected from the CONTEXT prospective cohort study and municipality characteristics were collected from Statistics South Africa.

Geospatial and temporal mapping of detectable HIV-1 viral loads amid dolutegravir rollout in KwaZulu-Natal, South Africa.

South Africa rolled out dolutegravir (DTG) as first-line antiretroviral therapy (ART) in December 2019 to overcome high rates of pretreatment non-nucleoside reverse transcriptase inhibitor drug resistance. In the context of transition to DTG-based ART, this study spatiotemporally analysed detectable HIV viral loads (VLs) prior to- and following DTG rollout in public-sector healthcare facilities in KwaZulu-Natal (KZN) province, the epicentre of the HIV epidemic in South Africa. We retrospectively curated a HIV VL database using de-identified routine VL data obtained from the National Health Laboratory Service for the period January 2018 to June 2022.

The epidemiology, transmission, diagnosis, and management of drug-resistant tuberculosis-lessons from the South African experience.

Drug-resistant tuberculosis (DR-TB) threatens to derail tuberculosis control efforts, particularly in Africa where the disease remains out of control. The dogma that DR-TB epidemics are fueled by unchecked rates of acquired resistance in inadequately treated or non-adherent individuals is no longer valid in most high DR-TB burden settings, where community transmission is now widespread. A large burden of DR-TB in Africa remains undiagnosed due to inadequate access to diagnostic tools that simultaneously detect tuberculosis and screen for resistance.

Treatment of Multidrug-resistant or Rifampicin-resistant Tuberculosis With an All-oral 9-month Regimen Containing Linezolid or Ethionamide in South Africa: A Retrospective Cohort Study.

Background: In 2019, the South African tuberculosis program replaced ethionamide with linezolid as part of an all-oral 9-month regimen. We evaluated treatment outcomes for patients assigned to regimens including linezolid in 2019 and ethionamide in 2017.

Methods: This retrospective cohort study included patients treated for multidrug-resistant/rifampicin-resistant tuberculosis throughout South Africa between 1 January and 31 December 2017 and 1 January to 31 December 2019.

Differentiated service delivery framework for people with multidrug-resistant tuberculosis and HIV co-infection.

Introduction: For people living with HIV/AIDS, care is commonly delivered through Differentiated Service Delivery (DSD). Although people with multidrug-resistant tuberculosis (MDR-TB) and HIV/AIDS experience severe treatment associated challenges, there is no DSD model to support their treatment. In this study, we defined patterns of medication adherence and characterized longitudinal barriers to inform development of an MDR-TB/HIV DSD framework.

Incidence and prevalence of hypertension among HIV-TB co-infected participants accessing treatment: A five-year prospective cohort analysis.

Introduction: Hypertension is a leading risk factor for cardiovascular disease among people living with human immunodeficiency virus (PLWH). This study determined incidence and prevalence of hypertension among PLWH receiving antiretroviral therapy (ART).

Method: We prospectively followed-up 642 HIV and tuberculosis (TB) co-infected study participants from 2005-2013.

Rapid Diagnosis of Drug-Resistant Tuberculosis-Opportunities and Challenges.

Global tuberculosis (TB) eradication is undermined by increasing prevalence of emerging resistance to available drugs, fuelling ongoing demand for more complex diagnostic and treatment strategies. Early detection of TB drug resistance coupled with therapeutic decision making guided by rapid characterisation of pre-treatment and treatment emergent resistance remains the most effective strategy for averting Drug-Resistant TB (DR-TB) transmission, reducing DR-TB associated mortality, and improving patient outcomes. Solid- and liquid-based mycobacterial culture methods remain the gold standard for (MTB) detection and drug susceptibility testing (DST).

Opportunities and limitations of genomics for diagnosing bedaquiline-resistant tuberculosis: a systematic review and individual isolate meta-analysis.

Background: Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship with phenotypic Mycobacterium tuberculosis resistance. We did a systematic review to assess the maximal sensitivity of sequencing bedaquiline resistance-associated genes and evaluate the association between RAVs and phenotypic resistance, using traditional and machine-based learning techniques.

Clinical outcomes with second-line dolutegravir in people with virological failure on first-line non-nucleoside reverse transcriptase inhibitor-based regimens in South Africa: a retrospective cohort study.

Background: Dolutegravir (DTG) is recommended for second-line antiretroviral therapy (ART) after virological failure on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in people living with HIV in low-income and middle-income countries. We compared the effectiveness of DTG versus the previously recommended ritonavir-boosted lopinavir (LPV/r) regimen for second-line treatment in South Africa.

Methods: In this retrospective observational cohort study, we used routinely collected, de-identified data from 59 primary health-care facilities in eThekwini Municipality, KwaZulu-Natal, South Africa.

Drug-Resistant TB, HIV and COVID-19 Co-Infection: Case Reviews from Kwa-Zulu Natal, South Africa.

Background: Coronavirus disease (COVID-19) potentially exacerbates drug-resistant tuberculosis (DR-TB). We describe the clinical presentation and outcomes of three patients with human immunodeficiency virus (HIV), DR-TB and COVID-19.

Case One: A virologically suppressed 31-year-old man on antiretroviral therapy (ART) and multidrug-resistant (MDR)-TB treatment presented with mild COVID-19 and was hospitalised for 10 days of clinical monitoring, despite being clinically stable with normal baseline inflammatory markers.