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Objectives: Optimising medication adherence is one of the essential factors in reversing the tide of a TB-HIV syndemic in sub-Saharan Africa, especially South Africa. Impairment in key neurocognitive domains may impair patients' ability to maintain adherence to treatment, but the level of cognition and its relationship to HIV status has not been examined in individuals with drug-resistant TB. We therefore investigated performance on several key neurocognitive domains in relationship to HIV status in a multidrug-resistant tuberculosis patients (MDR-TB) sample.Methods: We enrolled microbiologically confirmed MDR-TB inpatients at a TB-specialist referral hospital in KwaZulu-Natal province, South Africa. We collected cross-sectional data on sociodemographic, clinical and neurocognitive function (e.g. attention, memory, executive functioning, language fluency, visual-spatial, eye-hand coordination). For the primary analysis, we excluded participants with major depressive episode/substance use disorder (MDE/SUD). We fitted adjusted Poisson regression models to explore the association between HIV and neurocognitive function.Results: We enrolled 200 people with MDR-TB; 33 had MDE/SUD, and data of 167 were analysed (151 HIV+, 16 HIV-). The mean age of participants was 34.2 years; the majority were female (83%), and 53% had not completed secondary school. There was evidence of impaired neurocognitive functioning across all domains in both HIV+/- study participants. Based on the regression analyses, individuals with co-infection (MDR-TB/HIV+), as well as those who had longer duration of hospital stays experienced significantly lower cognitive performance in several domains. Poor cognitive performance was significantly related to older age and lower educational attainment. The presence of major depression or substance use disorders did not influence the significance of the findings.Conclusions: Adults with MDR-TB have significant neurocognitive impairment, especially if HIV positive. An integrated approach is necessary in the management of MDR-TB as cognitive health influences the ability to adhere to chronic treatment, clinical outcomes and functionality. [ABSTRACT FROM AUTHOR]

To determine retention in HIV care for individuals not yet eligible for antiretroviral therapy (ART) and to explore factors associated with retention in a rural public health HIV program.HIV-infected adults (≥16 years) not yet eligible for ART, with CD4 cell count >200 cells per microliter from January 2007 to December 2007 were included in the analysis. Retention was defined by repeat CD4 count within 13 months. Factors associated with retention were assessed using logistic regression with clustering at clinic level.Four thousand two hundred twenty-three were included in the analysis (83.9% female). Overall retention was 44.9% with median time to return 201 days [interquartile range (IQR): 127-274]. Retention by initial CD4 count 201-350, 351-500, and >500 cells per microliter was 51.6% [95% confidence interval (CI): 49.1 to 54.0], 43.2% (95% CI: 40.5 to 45.9), and 34.9% (95% CI: 32.4 to 37.4), respectively. Compared with CD4 201-350 cells per microliter, higher initial CD4 count was significantly associated with lower odds of retention [CD4: 351-500 cells/μL adjusted odds ratio (aOR): 0.72, 95% CI: 0.62 to 0.84; CD4 >500 cells/μL aOR: 0.51, 95% CI: 0.44 to 0.60]. Male sex was independently associated with lower odds (aOR: 0.80, 95% CI: 0.67 to 0.96), and older age with higher odds of retention (for each additional year of age aOR: 1.03, 95% CI: 1.03 to 1.04).Retention in HIV care before eligibility for ART is poor, particularly for younger individuals and those at an earlier stage of infection. Further work to optimize and evaluate care and monitoring strategies is required to realize the full benefits of the rapid expansion of HIV programs in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background Medication adherence is known to challenge treatment of human immunodeficiency virus (HIV)/AIDS and multidrug-resistant tuberculosis (MDR-TB). We hypothesized that adherence using electronic dose monitoring (EDM) would identify an antiretroviral therapy (ART) adherence threshold for emergent ART resistance and predict treatment outcomes in patients with MDR-TB and HIV on ART and bedaquiline-containing TB regimens. Methods A prospective cohort of adults with MDR-TB and HIV on ART and initiating MDR-TB treatment with bedaquiline were enrolled at a public hospital in KwaZulu-Natal, South Africa (PRAXIS Study). Participants received separate EDM devices that measure adherence to bedaquiline and ART (nevirapine or lopinavir/ritonavir). Adherence was calculated cumulatively over 6 months. Participants were followed through completion of MDR-TB treatment. HIV genome sequencing was performed at baseline and 2 and 6 months on samples with HIV RNA ≥1000 copies/mL. Results From November 2016 through February 2018, 198 persons with MDR-TB and HIV were enrolled and followed (median, 17.2 months; interquartile range, 12.2–19.6). Eleven percent had baseline ART resistance mutations, and 7.5% developed emergent ART resistance at 6 months. ART adherence was independently associated with ART resistance and mortality. Modeling identified a significant (P <.001), linear association between ART adherence and emergent resistance, suggesting a strong association without a specific threshold. Conclusions Our findings highlight the need for ART resistance testing, especially in patients with MDR-TB and HIV, which is currently not the standard of care in resource-limited settings. Despite short follow-up duration, reduced ART adherence was significantly associated with emergent resistance and increased mortality. Clinical Trials Registration NCT03162107. [ABSTRACT FROM AUTHOR]

• The early COVID-19 epidemic in South Africa was highly heterogeneous looking at the epidemiological progression between major provinces. • Early transmission in KwaZulu-Natal (KZN) was associated with multiple international introductions of SARS-CoV-2. • The dominating lineages during this time of the epidemic were B.1 and B, which mainly originated from Europe. • Evidence for transmission clusters during the first month of the epidemic suggested locally acquired infection. • A clustered outbreak was linked to a major hospital outbreak in Durban, which inflated the early mortality in KZN. The Network for Genomic Surveillance in South Africa (NGS-SA) was formed to investigate the introduction and understand the early transmission dynamics of the SARS-CoV-2 epidemic in South-Africa. This paper presents the first results from this group, which is a molecular epidemiological study of the first 21 SARS-CoV-2 whole genomes sampled in the first port of entry – KwaZulu-Natal (KZN) – during the first month of the epidemic. By combining this with calculations of the effective reproduction number (R), it aimed to shed light on the patterns of infections in South Africa. Two of the largest provinces – Gauteng and KZN – had a slow growth rate for the number of detected cases, while the epidemic spread faster in the Western Cape and Eastern Cape. The estimates of transmission potential suggested a decrease towards R = 1 since the first cases and deaths, but a subsequent estimated R average of 1.39 between 6–18 May 2020. It was also demonstrated that early transmission in KZN was associated with multiple international introductions and dominated by lineages B1 and B. Evidence for locally acquired infections in a hospital in Durban within the first month of the epidemic was also provided. The COVID-19 pandemic in South Africa was very heterogeneous in its spatial dimension, with many distinct introductions of SARS-CoV2 in KZN and evidence of nosocomial transmission, which inflated early mortality in KZN. The epidemic at the local level was still developing and NGS-SA aimed to clarify the dynamics in South Africa and devise the most effective measures as the outbreak evolved. [ABSTRACT FROM AUTHOR]

Participatory visual research can offer critical insight into the experiences of those most affected by health issues. As these methods are increasingly used to research sensitive topics, there is a need for a clear ethical framework to guide best practice on the part of researchers and research ethics committees. Here we reflect on a project where we used digital storytelling as a participatory visual methodology to explore HIV treatment adherence in rural South Africa, with a focus on the ethical issues we encountered during the lifetime of the project. To ground our reflections, we use the framework for ethical research developed by Emanuel et al., and the adaptation of this framework for social science proposed by Wassenaar and Mamotte. We suggest that fellow PVM practitioners and REC members draw on this holistic framework to support the optimal application of PVM in health research. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission. It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level. This trial aims to evaluate the effect of ART initiated immediately after identification/diagnosis of HIV-infected individuals, regardless of CD4 count, on HIV incidence in the surrounding population. The primary outcome of the overall trial will be HIV incidence over two years. Secondary outcomes will include i) socio-behavioural outcomes (acceptability of repeat HIV counselling and testing, treatment acceptance and linkage to care, sexual partnerships and quality of life); ii) clinical outcomes (mortality and morbidity, retention into care, adherence to ART, virologic failure and acquired HIV drug resistance), iii) cost-effectiveness of the intervention. The first phase will specifically focus on the trial's secondary outcomes.Methods/design: A cluster-randomised trial in 34 (2 × 17) clusters within a rural area of northern KwaZulu-Natal (South Africa), covering a total population of 34,000 inhabitants aged 16 years and above, of whom an estimated 27,200 would be HIV-uninfected at start of the trial. The first phase of the trial will include ten (2 × 5) clusters. Consecutive rounds of home-based HIV testing will be carried out. HIV-infected participants will be followed in dedicated trial clinics: in intervention clusters, they will be offered immediate ART initiation regardless of CD4 count and clinical stage; in control clusters they will be offered ART according to national treatment eligibility guidelines (CD4 <350 cells/μL, World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis). Following proof of acceptability and feasibility from the first phase, the trial will be rolled out to further clusters.Discussion: We aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level. Data collected from the participants at home and in the clinics will inform understanding of socio-behavioural, economic and clinical impacts of the intervention as well as feasibility and generalizability.Trial Registration: Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974. [ABSTRACT FROM AUTHOR]

Unlabelled: Background: Although access to life-saving treatment for patients infected with HIV in South Africa has improved substantially since 2004, treating all eligible patients (universal access) remains elusive. As the prices of antiretroviral drugs have dropped over the past years, availability of human resources may now be the most important barrier to achieving universal access to HIV treatment in Africa. We quantify the number of HIV health workers (HHWs) required to be added to the current HIV workforce to achieve universal access to HIV treatment in South Africa, under different eligibility criteria.Methods: We performed a time and motion study in three HIV clinics in a rural, primary care-based HIV treatment program in KwaZulu-Natal, South Africa, to estimate the average time per patient visit for doctors, nurses, and counselors. We estimated the additional number of HHWs needed to achieve universal access to HIV treatment within one year.Results: For universal access to HIV treatment for all patients with a CD4 cell count of ≤350 cells/μl, an additional 2,200 nurses, 3,800 counselors, and 300 doctors would be required, at additional annual salary cost of 929 million South African rand (ZAR), equivalent to US$ 141 million. For universal treatment ('treatment as prevention'), an additional 6,000 nurses, 11,000 counselors, and 800 doctors would be required, at an additional annual salary cost of ZAR 2.6 billion (US$ 400 million).Conclusions: Universal access to HIV treatment for patients with a CD4 cell count of ≤350 cells/μl in South Africa may be affordable, but the number of HHWs available for HIV treatment will need to be substantially increased. Treatment as prevention strategies will require considerable additional financial and human resources commitments. [ABSTRACT FROM AUTHOR]