Impact of vaccine type on HIV-1 vaccine elicited antibody durability and B cell gene signature.

Efficacious HIV-1 vaccination requires elicitation of long-lived antibody responses. However, our understanding of how different vaccine types elicit durable antibody responses is lacking. To assess the impact of vaccine type on antibody responses, we measured IgG isotypes against four consensus HIV antigens from 2 weeks to 10 years post HIV-1 vaccination and used mixed effects models to estimate half-life of responses in four human clinical trials.

Age-Specific Risk Scores Do Not Improve HIV-1 Prediction Among Women in South Africa.

Background: HIV-1 risk scoring tools could help target provision of prevention modalities such as pre-exposure prophylaxis. Recent research suggests that risk scores for women aged 18-45 may not predict risk well among young women aged 18-24. We evaluated the predictive performance of age-specific risk scores compared with the existing non-age-specific VOICE risk score, developed for women aged 18-45.

Estimating the yield of tuberculosis from key populations to inform targeted interventions in South Africa: a scoping review.

Introduction: Tuberculosis (TB) case finding strategies are recommended to increase yield for TB in key populations. Several key populations are identified in the literature, but techniques for estimating yield and prioritising interventions are needed.

Methods: We conducted a scoping review of existing evidence on TB burden to assess contribution of key populations to the TB epidemic in South Africa.

"Knock Knock": a qualitative study exploring the experience of household contacts on home visits and their attitude towards people living with TB in South Africa.

Background: Household contract tracing (HHCT) is an important strategy for active tuberculosis case finding and offers an opportunity for testing of other diseases such as HIV. However, there is limited data on the patient-centered approach to HHCT. Our study aimed to describe experiences and preferences of household contacts (HHCs) for HHCT.

HIV prevalence and the cascade of care in five South African correctional facilities.

Background: South Africa is home to the world's largest HIV epidemic. Throughout the world, incarcerated individuals have a higher prevalence of HIV than the general public, and South Africa has one of the highest rates of incarceration in sub-Saharan Africa. In spite of this, little has been published about the burden of HIV and how care is delivered in South African correctional facilities.

Youth Preferences for HIV Testing in South Africa: Findings from the Youth Action for Health (YA4H) Study Using a Discrete Choice Experiment.

We conducted a discrete choice experiment (DCE) and quantified preferences for HIV testing among South African youth (Nov 2018 to Mar 2019). Six attributes and levels were identified through qualitative methods: source of HIV information; incentive amount and type; social support; testing method; and location. Each participant chose one of two options that comprised six attributes across 18 questions.

HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance.

We have previously reported on HIV-1 infected patients who fail anti-retroviral therapy but manage to re-suppress without a regimen change despite harbouring major drug resistance mutations. Here we explore phenotypic drug resistance in such patients in order to better understand this phenomenon. Patients (n = 71) failing a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, but who subsequently re-suppressed on the same regimen, were assessed for HIV-1 genotypic drug resistance through Sanger sequencing.

Outcomes of HIV-positive patients with non-tuberculous mycobacteria positive culture who received anti-tuberculous treatment in Botswana: Implications of using diagnostic algorithms without non-tuberculous mycobacteria.

Background: Patients with non-tuberculous mycobacteria (NTM) or Mycobacterium tuberculosis (MTB) pulmonary disease may have similar clinical presentation. The potential for misdiagnosis and inappropriate treatment exists in settings with limited testing capacity for Xpert® MTB/RIF (Xpert), phenotypic culture and NTM speciation. We describe treatment outcomes among people living with HIV (PLHIV) who received anti-tuberculosis treatment and were found to have NTM or MTB positive sputum cultures.

Predictors of silicosis and variation in prevalence across mines among employed gold miners in South Africa.

Background: The stated intention to eliminate silicosis from the South African goldmining industry as well as current programmes to find and compensate ex-miners with silicosis require an understanding of variation in silicosis prevalence across the industry. We aimed to identify the predictors of radiological silicosis in a large sample of working miners across gold mines in South Africa.

Methods: Routine surveillance chest radiographs were collected from 15 goldmine "clusters" in a baseline survey undertaken in preparation for a separate tuberculosis isoniazid prophylaxis trial.

Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials.

Background: DNA plasmids promise a pragmatic alternative to viral vectors for prime-boost HIV-1 vaccines. We evaluated DNA plasmid versus canarypox virus (ALVAC) primes in 2 randomized, double-blind, placebo-controlled trials in southern Africa with harmonized trial designs. HIV Vaccine Trials Network (HVTN) 111 tested DNA plasmid prime by needle or needleless injection device (Biojector) and DNA plasmid plus gp120 protein plus MF59 adjuvant boost.

Effects of Depot Medroxyprogesterone Acetate, Copper Intrauterine Devices, and Levonorgestrel Implants on Early HIV Disease Progression.

Limited data exist on the effects of contraceptives on HIV disease progression. We studied the association between intramuscular injectable depot medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (IUD), and the levonorgestrel (LNG) implant on markers of HIV disease progression at the time of HIV detection and 3 months postdetection and time from detection to CD4 count <350 cells/mm. Among women initiating antiretroviral therapy (ART), we studied the effect of contraceptive group on time from ART initiation to viral load (VL) <40 copies/mL.

Rapid TB diagnostic service and community action to FIND.TREAT.ALL#EndTB, Maputo, Mozambique, 2013-2018.

Finding and treating all tuberculosis (TB) patients is crucial for ending TB. We investigated whether rapid diagnostic turnaround time (TAT) and patient tracking could increase TB treatment initiation in Maputo, Mozambique. Among 3329 TB patients newly diagnosed by the University Eduardo Mondlane-Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling/Anti-Personnel Landmines Detection Product Development (APOPO) Laboratory between 2013 and 2018, on average 61% were verifiably linked to care.

Resistance-Conferring Mutations on Whole-Genome Sequencing of Fluoroquinolone-resistant and -Susceptible Mycobacterium tuberculosis Isolates: A Proposed Threshold for Identifying Resistance.

Background: Fluoroquinolone resistance in Mycobacterium tuberculosis (Mtb) is conferred by DNA gyrase mutations, but not all fluoroquinolone-resistant Mtb isolates have mutations detected. The optimal allele frequency threshold to identify resistance-conferring mutations by whole-genome sequencing is unknown.

Methods: Phenotypically ofloxacin-resistant and lineage-matched ofloxacin-susceptible Mtb isolates underwent whole-genome sequencing at an average coverage depth of 868 reads.

Sensitivity of the lateral flow urine lipoarabinomannan assay in ambulant adults with advanced HIV disease: data from the TB Fast Track study.

Background: WHO guidelines recommend the lateral flow urine lipoarabinomannan assay (LF-LAM) for TB diagnosis in hospitalised HIV-positive individuals. The role of LF-LAM among ambulant patients remains less well defined. We investigated the sensitivity of LF-LAM among ambulant HIV-positive adults in primary health clinics in South Africa.

Challenges influencing nurse-initiated management of antiretroviral therapy training and implementation in Ngaka Modiri Molema district, North West province.

Background: The increasing number of people testing human immunodeficiency virus positive and who demand antiretroviral therapy (ART) prompted the Department of Health to adopt World Health Organization's task shifting where professional nurses (PNs) initiate ART rather than doctors. This resulted in decentralisation of services to primary healthcare (PHC), generating a need to capacitate PNs on nurse-initiated-management of ART (NIMART). The impact of NIMART was assessed and even though there was an increased number of patients on ART, the quality of care is of serious concern.

'They are inconveniencing us' - exploring how gaps in patient education and patient centred approaches interfere with TB treatment adherence: perspectives from patients and clinicians in the Free State Province, South Africa.

Background: Tuberculosis (TB) treatment loss to follow up (LTFU) plays an important contributory role to the staggering TB epidemic in South Africa. Reasons for treatment interruption are poorly understood. Treatment interruption appears to be the culmination of poor health literacy of patients and inadequate health education provided by clinicians.

Once-weekly rifapentine and isoniazid for tuberculosis prevention in patients with HIV taking dolutegravir-based antiretroviral therapy: a phase 1/2 trial.

Background: Short-course preventive therapy with 12 doses of once-weekly rifapentine (900 mg) plus isoniazid (900 mg) could greatly improve tuberculosis control, especially in areas with high co-endemicity with HIV. However, a small previous trial of such therapy with dolutegravir in healthy, HIV-negative adults was halted early after two of the four patients developed serious adverse events. Because of the potential use of this therapy, and variable safety outcomes of tuberculosis drugs seen in patients with and without HIV, we aimed to characterise safety, pharmacokinetics, and virological suppression in adults who are HIV positive.

Examining Approaches to Estimate the Prevalence of Catastrophic Costs Due to Tuberculosis from Small-Scale Studies in South Africa.

Background And Objective: In context of the End TB goal of zero tuberculosis (TB)-affected households encountering catastrophic costs due to TB by 2020, the estimation of national prevalence of catastrophic costs due to TB is a priority to inform programme design. We explore approaches to estimate the national prevalence of catastrophic costs due to TB from existing datasets as an alternative to nationally representative surveys.

Methods: We obtained, standardized and merged three patient-level datasets from existing studies on patient-incurred costs due to TB in South Africa.

Symptom and digital chest X-ray TB screening in South African prisons: yield and cost-effectiveness.

Correctional inmates are at a high risk of tuberculosis (TB). The optimal approach to screening this population is unclear. We retrospectively reviewed records from TB screening in 64 correctional facilities in South Africa between January 2015 and July 2016.

Observational study of continuity of HIV care following release from correctional facilities in South Africa.

Background: We sought to describe linkage to care, ART continuity, and factors associated with linkage to care among people with HIV following release from incarceration in South Africa.

Methods: We conducted a study of South African correctional service community reentrants who were receiving ART at the time of release. The study was implemented in three of 46 correctional service management areas.

Conceptual framework for strengthening nurse-initiated management of antiretroviral therapy training and implementation in North West province.

Background: The implementation of nurse-initiated management of antiretroviral therapy (NIMART) management training is a challenge in the primary health care (PHC). It is evident from the literature reviewed and the data obtained from the North West province that gaps still exist. There is no conceptual framework providing guidance to NIMART training and implementation.

Effect of Xpert MTB/RIF testing introduction and favorable outcome predictors for tuberculosis treatment among HIV infected adults in rural southern Mozambique. A retrospective cohort study.

Background: Global roll out of Xpert MTB/RIF technology has resulted in dramatic changes in TB diagnosis. However, benefits in resource-limited, high-burden TB/HIV settings, remain to be verified. In this paper we describe the characteristics of a large cohort of TB patients in a rural hospital in Southern Mozambique before and after Xpert MTB/RIF introduction, together with some determinants of favorable treatment outcome.

Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines.

Background: HVTN 100 evaluated the safety and immunogenicity of an HIV subtype C pox-protein vaccine regimen, investigating a 12-month booster to extend vaccine-induced immune responses.

Methods And Findings: A phase 1-2 randomized double-blind placebo-controlled trial enrolled 252 participants (210 vaccine/42 placebo; median age 23 years; 43% female) between 9 February 2015 and 26 May 2015. Vaccine recipients received ALVAC-HIV (vCP2438) alone at months 0 and 1 and with bivalent subtype C gp120/MF59 at months 3, 6, and 12.

Lessons learnt conducting minimally invasive autopsies in private mortuaries as part of HIV and tuberculosis research in South Africa.

Current estimates of the burden of tuberculosis (TB) disease and cause-specific mortality in human immunodeficiency virus (HIV) positive people rely heavily on indirect methods that are less reliable for ascertaining individual-level causes of death and on mathematical models. Minimally invasive autopsy (MIA) is useful for diagnosing infectious diseases, provides a reasonable proxy for the gold standard in cause of death ascertainment (complete diagnostic autopsy) and, used routinely, could improve cause-specific mortality estimates. From our experience in performing MIAs in HIV-positive adults in private mortuaries in South Africa (during the Study), we describe the challenges we faced and make recommendations for the conduct of MIA in future studies or surveillance programmes, including strategies for effective communication, approaches to obtaining informed consent, risk management for staff and efficient preparation for the procedure.