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Background Empirical tuberculosis (TB) treatment in human immunodeficiency virus (HIV)–positive inpatients is common and may undermine the impact of new diagnostics. We sought to describe empirical TB treatment and compare characteristics and outcomes with patients treated for TB after screening. Methods This was a retrospective observational cohort study of HIV-positive inpatients treated empirically for TB prior to TB screening. Data on clinical characteristics, investigations, and outcomes were collected from medical records. Comparison cohorts with microbiologically confirmed or empirical TB treatment after TB screening with Xpert MTB/RIF and urine lipoarabinomannan assays were taken from South African Screening for Tuberculosis to Reduce AIDS-Related Mortality in Hospitalized Patients in Africa (STAMP) trial site. In-hospital mortality was compared using a competing-risks analysis adjusted for age, sex, and CD4 cell count. Results Between January 2016 and September 2017, 100 patients excluded from STAMP were treated for TB empirically prior to TB screening. After enrollment in STAMP and TB screening, 240 of 1177 (20.4%) patients received TB treatment, of whom 123 had positive TB tests and 117 were treated empirically. Characteristics were similar among early empirically treated patients and those treated after TB screening. 50% of early empirical TB treatment was based on radiological investigations, 22% on cerebrospinal or pleural fluid testing, and 28% on clinical features alone. Only 11 of 100 empirically treated patients had subsequent microbiological confirmation. In-hospital mortality was lower in patients with microbiologically confirmed TB compared to those treated empirically (adjusted subdistribution hazard ratio, 0.5 [95% confidence interval,.3–.9). Conclusions Empirical TB treatment remains common in severely ill HIV-positive inpatients. These patients may benefit from TB screening using existing rapid diagnostics, both to improve confirmation of TB disease and reduce overtreatment for TB. [ABSTRACT FROM AUTHOR]

Background Tuberculosis (TB) is the major killer of people living with human immunodeficiency virus (HIV) globally, with suboptimal diagnostics and management contributing to high case-fatality rates. Methods A prospective cohort of patients with confirmed TB (Xpert MTB/RIF and/or Determine TB-LAM Ag positive) identified through screening HIV-positive inpatients with sputum and urine diagnostics in Malawi and South Africa (Rapid urine-based Screening for Tuberculosis to reduce AIDS Related Mortality in hospitalized Patients in Africa [STAMP] trial). Urine was tested prospectively (intervention) or retrospectively (standard of care arm). We defined baseline clinical phenotypes using hierarchical cluster analysis, and also used Cox regression analysis to identify associations with early mortality (≤56 days). Results Of 322 patients with TB confirmed between October 2015 and September 2018, 78.0% had ≥1 positive urine test. Antiretroviral therapy (ART) coverage was 80.2% among those not newly diagnosed, but with median CD4 count 75 cells/µL and high HIV viral loads. Early mortality was 30.7% (99/322), despite near-universal prompt TB treatment. Older age, male sex, ART before admission, poor nutritional status, lower hemoglobin, and positive urine tests (TB-LAM and/or Xpert MTB/RIF) were associated with increased mortality in multivariate analyses. Cluster analysis (on baseline variables) defined 4 patient subgroups with early mortality ranging from 9.8% to 52.5%. Although unadjusted mortality was 9.3% lower in South Africa than Malawi, in adjusted models mortality was similar in both countries (hazard ratio, 0.9; P =.729). Conclusions Mortality following prompt inpatient diagnosis of HIV-associated TB remained unacceptably high, even in South Africa. Intensified management strategies are urgently needed, for which prognostic indicators could potentially guide both development and subsequent use. [ABSTRACT FROM AUTHOR]

Background: Current diagnostics for HIV-associated tuberculosis are suboptimal, with missed diagnoses contributing to high hospital mortality and approximately 374 000 annual HIV-positive deaths globally. Urine-based assays have a good diagnostic yield; therefore, we aimed to assess whether urine-based screening in HIV-positive inpatients for tuberculosis improved outcomes.Methods: We did a pragmatic, multicentre, double-blind, randomised controlled trial in two hospitals in Malawi and South Africa. We included HIV-positive medical inpatients aged 18 years or more who were not taking tuberculosis treatment. We randomly assigned patients (1:1), using a computer-generated list of random block size stratified by site, to either the standard-of-care or the intervention screening group, irrespective of symptoms or clinical presentation. Attending clinicians made decisions about care; and patients, clinicians, and the study team were masked to the group allocation. In both groups, sputum was tested using the Xpert MTB/RIF assay (Xpert; Cepheid, Sunnyvale, CA, USA). In the standard-of-care group, urine samples were not tested for tuberculosis. In the intervention group, urine was tested with the Alere Determine TB-LAM Ag (TB-LAM; Alere, Waltham, MA, USA), and Xpert assays. The primary outcome was all-cause 56-day mortality. Subgroup analyses for the primary outcome were prespecified based on baseline CD4 count, haemoglobin, clinical suspicion for tuberculosis; and by study site and calendar time. We used an intention-to-treat principle for our analyses. This trial is registered with the ISRCTN registry, number ISRCTN71603869.Findings: Between Oct 26, 2015, and Sept 19, 2017, we screened 4788 HIV-positive adults, of which 2600 (54%) were randomly assigned to the study groups (n=1300 for each group). 13 patients were excluded after randomisation from analysis in each group, leaving 2574 in the final intention-to-treat analysis (n=1287 in each group). At admission, 1861 patients were taking antiretroviral therapy and median CD4 count was 227 cells per μL (IQR 79-436). Mortality at 56 days was reported for 272 (21%) of 1287 patients in the standard-of-care group and 235 (18%) of 1287 in the intervention group (adjusted risk reduction [aRD] -2·8%, 95% CI -5·8 to 0·3; p=0·074). In three of the 12 prespecified, but underpowered subgroups, mortality was lower in the intervention group than in the standard-of-care group for CD4 counts less than 100 cells per μL (aRD -7·1%, 95% CI -13·7 to -0·4; p=0.036), severe anaemia (-9·0%, -16·6 to -1·3; p=0·021), and patients with clinically suspected tuberculosis (-5·7%, -10·9 to -0·5; p=0·033); with no difference by site or calendar period. Adverse events were similar in both groups.Interpretation: Urine-based tuberculosis screening did not reduce overall mortality in all HIV-positive inpatients, but might benefit some high-risk subgroups. Implementation could contribute towards global targets to reduce tuberculosis mortality.Funding: Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, and the Wellcome Trust. [ABSTRACT FROM AUTHOR]

Background: Although HIV testing and counseling (HTC) uptake has increased dramatically in Africa, facility-based services are unlikely to ever meet ongoing need to the full. A major constraint in scaling up community and home-based HTC services is the unacceptability of receiving HTC from a provider known personally to prospective clients. We investigated the potential of supervised oral HIV self-testing from this perspective. Methods and Findings: Adult members of 60 households and 72 members of community peer groups in urban Blantyre, Malawi, were selected using population-weighted random cluster sampling. Participants were offered self-testing plus confirmatory HTC (parallel testing with two rapid finger-prick blood tests), standard HTC alone, or no testing. 283 (95.6%) of 298 selected adults participated, including 136 (48.0%) men. 175 (61.8%) had previously tested (19 known HIV positive), although only 64 (21.5%) within the last year. HIV prevalence was 18.5%. Among 260 (91.9%) who opted to self-test after brief demonstration and illustrated instructions, accuracy was 99.2% (two false negatives). Although 98.5% rated the test "not hard at all to do," 10.0% made minor procedural errors, and 10.0% required extra help. Most participants indicated willingness to accept self-test kits, but not HTC, from a neighbor (acceptability 94.5% versus 46.8%, p = 0.001). Conclusions: Oral supervised self-testing was highly acceptable and accurate, although minor errors and need for supervisory support were common. This novel option has potential for high uptake at local community level if it can be supervised and safely linked to counseling and care. [ABSTRACT FROM AUTHOR]

The effect of HIV-1 on other infectious diseases in Africa is an increasing public health concern. In this review, we describe the role that three major infectious diseases-malaria, sexually transmitted diseases (STDs), and tuberculosis- have had in the HIV-1 epidemic. The high prevalence of untreated STD infections has been a major factor facilitating the spread of HIV-1 in Africa; with the synergistic interaction between HIV-1 transmission and genital herpes being of especial concern for control of both diseases. Increased susceptibility to tuberculosis after infection with HIV-1 has led to a rising incidence and threat of increased transmission of tuberculosis. Clinical malaria occurs with an increased frequency and severity in HIV-1-infected individuals, especially during pregnancy. As with tuberculosis, STDs, and other communicable HIV-1-associated diseases, the net effect of HIV-1 might include increased rates of malaria transmission across communities. In addition to enhancing access to HIV-1 prevention and care, public health surveillance and control programmes should be greatly intensified to cope with the new realities of infectious disease control in Africa. [ABSTRACT FROM AUTHOR]

Introduction: HIV self‐testing (HIVST) was first proposed as an additional option to standard HIV testing services in the 1980s. By 2015, two years after the first HIVST kit was approved for the American market and the year in which Unitaid invested in the "HIV Self‐Testing AfRica (STAR) Initiative," HIVST remained unexplored with negligible access in low‐ and middle‐income countries (LMIC). However, rapid progress had been made. This commentary outlines the interlinked market, regulatory and policy barriers that had inhibited product development and kept HIVST out of LMIC policy. We detail the components of STAR that enabled rapid HIVST scale‐up, including critical investments in implementation, research, market forecasting, and engagement with manufacturers and regulators. Discussion: The STAR Initiative has generated crucial information about how to distribute HIVST products effectively, ethically and efficiently. Service delivery models range from clinic‐based distribution to workplace and partner‐delivered approaches to reach first‐time male testers, to community outreach to sex workers and general population "hotspots." These data directly informed supportive policy, notably the 2016 WHO guidelines strongly recommending HIVST as an additional testing approach, and regulatory change through support for WHO prequalification of the first HIVST kit in 2017. In July 2015, only two countries had national HIVST policies and were implementing HIVST. Three years later, 59 countries have policies, actively implemented in 28, with an additional 53 countries reporting policies under development. By end‐November 2018 several quality‐assured HIVST products had been registered, including two WHO prequalified tests. STAR Initiative countries have drafted regulations governing in vitro diagnostics, including HIVST products. With enabling policies, pre‐qualification and regulations in place, donor procurement of kits has increased rapidly, to a forecasted estimate of 16 million HIVST kits procured by 2020. Conclusions: The STAR Initiative provided a strong foundation to introduce HIVST in LMICs and allow for rapid scale‐up based on the wealth of multi‐country evidence gathered. Together with sustained coordination and acceleration of market development work, HIVST can help address the testing gap and provide a focused and cost‐effective means to expand access to treatment and prevention services. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of undiagnosed HIV is declining in Africa, and various HIV testing approaches are finding lower positivity rates. In this context, the epidemiological impact and cost‐effectiveness of community‐based HIV self‐testing (CB‐HIVST) is unclear. We aimed to assess this in different sub‐populations and across scenarios characterized by different adult HIV prevalence and antiretroviral treatment programmes in sub‐Saharan Africa. Methods: The synthesis model was used to address this aim. Three sub‐populations were considered for CB‐HIVST: (i) women having transactional sex (WTS); (ii) young people (15 to 24 years); and (iii) adult men (25 to 49 years). We assumed uptake of CB‐HIVST similar to that reported in epidemiological studies (base case), or assumed people use CB‐HIVST only if exposed to risk (condomless sex) since last HIV test. We also considered a five‐year time‐limited CB‐HIVST programme. Cost‐effectiveness was defined by an incremental cost‐effectiveness ratio (ICER; cost‐per‐disability‐adjusted life‐year (DALY) averted) below US$500 over a time horizon of 50 years. The efficiency of targeted CB‐HIVST was evaluated using the number of additional tests per infection or death averted. Results: In the base case, targeting adult men with CB‐HIVST offered the greatest impact, averting 1500 HIV infections and 520 deaths per year in the context of a simulated country with nine million adults, and impact could be enhanced by linkage to voluntary medical male circumcision (VMMC). However, the approach was only cost‐effective if the programme was limited to five years or the undiagnosed prevalence was above 3%. CB‐HIVST to WTS was the most cost‐effective. The main drivers of cost‐effectiveness were the cost of CB‐HIVST and the prevalence of undiagnosed HIV. All other CB‐HIVST scenarios had an ICER above US$500 per DALY averted. Conclusions: CB‐HIVST showed an important epidemiological impact. To maximize population health within a fixed budget, CB‐HIVST needs to be targeted on the basis of the prevalence of undiagnosed HIV, sub‐population and the overall costs of delivering this testing modality. Linkage to VMMC enhances its cost‐effectiveness. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is now established in Africa, with more than 63 000 cases and 2200 deaths in 53 countries, as of May 11, 2020.[1] Fragile health systems leave African countries vulnerable to the anticipated surge in severely ill patients with COVID-19, despite much younger populations. We used Spiegelhalter's approach to compare age-group specific infection fatality ratios from COVID-19 to background (non-COVID-19) mortality risk in Malawi, South Africa, the UK, and India.[[3]] This assumes COVID-19 infection fatality ratios similar to China, but true age-specific case-fatality rates might be higher with fragile health systems. [Extracted from the article]