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Tuberculosis (TB) is a major killer, causing [approximately equal to] 1,4 million deaths worldwide annually (1), making it second only to coronavirus disease (COVID-19) as the biggest cause of infectious [...]

Tuberculosis (TB) is the leading infectious cause of death worldwide; there were an estimated 1.3 million deaths during 2017 (1). Approximately 25% of the world's population is infected with Mycobacterium [...]

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. Keywords: HIV testing, community-based HIV self-testing; cost-effectiveness; mathematical modelling; HIV; benefits and cost, 1 | INTRODUCTION The ambitious UNAIDS targets, set in 2014, of diagnosing 90% of people living with HIV, having 90% of those diagnosed on antiretroviral treatment (ART) and having virological [...]

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 additiona 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. Keywords: HIV testing; HIV self-testing; market shaping; scale-up; prevention; linkage to care; cost effectiveness, 1 | INTRODUCTION HIV testing is the gateway to treatment and care and expanded prevention coverage. The first of the United Nations' 90-90-90 Fast Track targets to end the HIV [...]

Introduction: HIV self-testing (HIVST) provides couples and individuals with a discreet, convenient and empowering testing option. As with all HIV testing, potential harms must be anticipated and mitigated to optimize individual and public health benefits. Here, we describe social harms (SHs) reported during HIVST implementation in Malawi, and propose a framework for grading and responding to harms, according to their severity. Methods: We report findings from six HIVST implementation studies in Malawi (2011 to 2017) that included substudies investigating SH reports. Qualitative methods included focus group discussions, in-depth interviews and critical incident interviews. Earlier studies used intensive quantitative methods (post-test questionnaires for intimate partner violence, household surveys, investigation of all deaths in HIVST communities). Later studies used post-marketing reporting with/without community engagement. Pharmacovigilance methodology (whereby potentially life-threatening/changing events are defined as 'serious') was used to grade SH severity, assuming more complete passive reporting for serious events. Results: During distribution of 175,683 HIVST kits, predominantly under passive SH reporting, 25 serious SHs were reported from 19 (0.011%) self-testers, including 15 partners in eight couples with newly identified HIV discordancy, and one perinatally infected adolescent. There were no deaths or suicides. Marriage break-up was the most commonly reported serious SH (sixteen individuals; eight couples), particularly among serodiscordant couples. Among new concordant HIV-positive couples, blame and frustration was common but rarely (one episode) led to serious SHs. Among concordant HIV-negative couples, increased trust and stronger relationships were reported. Coercion to test or disclose was generally considered 'well-intentioned' within established couples. Women felt empowered and were assertive when offering HIVST test kits to their partners. Some women who persuaded their partner to test, however, did report SHs, including verbal or physical abuse and economic hardship. Conclusions: After more than six years of large-scale HIVST implementation and in-depth investigation of SHs in Malawi, we identified approximately one serious reported SH per 10,000 HIVST kits distributed, predominantly break-up of married serodiscordant couples. Both 'active' and 'passive' reporting systems identified serious SH events, although with more complete capture by 'active' systems. As HIVST is scaled-up, efforts to support and further optimize community-led SH monitoring should be prioritized alongside HIVST distribution. Keywords: HIV/AIDS; HIV self-test; HIV testing; social harms; Malawi, 1 | INTRODUCTION Despite concerted efforts to scale-up HIV testing services, in 2017, approximately 25% of people with HIV remain undiagnosed [1]. Globally, men, young people and key populations are [...]

Introduction: HIV self-testing (HIVST) is recommended by the World Health Organization in addition to other testing modalities to increase uptake of HIV testing, particularly among harder-to-reach populations. This study provides the first empirica evidence of the costs of door-to-door community-based HIVST distribution in Malawi, Zambia and Zimbabwe. Methods: HIVST kits were distributed door-to-door in 71 sites across Malawi, Zambia and Zimbabwe from June 2016 to May 2017. Programme expenditures, supplemented by on-site observation and monitoring and evaluation data were used to estimate total economic and unit costs of HIVST distribution, by input and site. Inputs were categorized into start-up, capital and recurrent costs. Sensitivity and scenario analyses were performed to assess the impact of key parameters on unit costs. Results: In total, 152,671, 103,589 and 93,459 HIVST kits were distributed in Malawi, Zambia and Zimbabwe over 12, 11 and 10 months respectively. Across these countries, 43% to 51% of HIVST kits were distributed to men. The average cost per HIVST kit distributed was US$8.15, US$16.42 and US$13.84 in Malawi, Zambia and Zimbabwe, respectively, with pronounced intersite variation within countries driven largely by site-level fixed costs. Site-level recurrent costs were 70% to 92% of full costs and 20% to 62% higher than routine HIV testing services (HTS) costs. Personnel costs contributed from 26% to 52% of total costs across countries reflecting differences in remuneration approaches and country GDP. Conclusions: These early door-to-door community HIVST distribution programmes show large potential, both for reaching untested populations and for substantial economies of scale as HIVST programmes scale-up and mature. From a societal perspective, the costs of HIVST appear similar to conventional HTS, with the higher providers' costs substantially offsetting user costs. Future approaches to minimizing cost and/or maximize testing coverage could include unpaid door-to-door community-led distribution to reach end-users and integrating HIVST into routine clinical services via direct or secondary distribution strategies with lower fixed costs. Keywords: HIV self-testing; costs and cost analysis; community; Malawi; Zambia; Zimbabwe, 1 | INTRODUCTION In East and Southern Africa, freely available HIV services have led to a 42% reduction in AIDS-related deaths between 2010 and 2016. Despite such gains, 24% of [...]

Introduction: Social, structural and systems barriers inhibit uptake of HIV testing. HIV self-testing (HIVST) has shown promising uptake by otherwise underserved priority groups including men, young people and first-time testers. Here, we use characteristics of HIVST kit recipients to investigate delivery to these priority groups during HIVST scale-up in three African countries. Methods: Kit distributors collected individual-level age, sex and testing history from all clients. These data were aggregated and analysed by country (Malawi, Zambia and Zimbabwe) for five distribution models: local community-based distributor (CBD: door-to-door, street and local venues), workplace distribution (WD), integration into HIV testing services (IHTS), or pubic health facilities (IPHF) and during demand creation for voluntary male medical circumcision (VMMC). Used kits were collected and re-read from CBD and IHTS recipients. Results: Between May 2015 and July 2017, 628,705 HIVST kits were distributed in Malawi (172,830), Zambia (190,787) and Zimbabwe (265,091). Community-based models, the first to be established, accounted for 519,658 (82.7%) of kits distributed, with 275,419 (53.0%) used kits returned. Subsequent model diversification delivered 54,453 (8.7%) test-kits through IHTS, 23,561 (3.7%) through VMMC, 21,183 (3.4%) through IPHF and 9850 (1.7%) through WD. Men took 294,508 (48.2%) kits, and 263,073 (43.1%) went to young people (16 to 24 years). A higher proportion of male self-testers (65,577; 22.3%) were first-time testers than women (54,096; 17.1%) with this apparent in Zimbabwe (16.2% vs. 11.4%), Zambia (25.4% vs. 17.7%) and Malawi (27.9% vs. 25.9%). The highest proportions of first-time testers were in young (16 to 24 years) and older (>50 years) men (country-ranges: 18.7% to 35.9% and 13.8% to 26.8% respectively). Most IHTS clients opted for HIVST in preference to standard HTS in each of 12 delivery sites, with those selecting HIVST having lower HIV prevalence, potentially due to self-selection. Conclusions: HIVST delivered at scale using several different models reached a high proportion of men, young people and first-time testers in Malawi, Zambia and Zimbabwe, some of whom may not have tested otherwise. As men and young people have limited uptake under standard facility-and community-based HIV testing, innovative male- and youth-sensitive approaches like HIVST may be essential to reaching UNAIDS fast-track targets for 2020. Keywords: HIV self-testing; HIV testing; men; adolescents; stigma; Malawi; Zambia; Zimbabwe, 1 | INTRODUCTION In 2016, 36.7 million people were living with HIV (PLHIV), with 1.8 million new HIV infections and one million HIV/AIDS-related deaths [1]. Despite substantial progress toward the [...]

Introduction: New HIV testing strategies are needed to reach the United Nations' 90-90-90 target. HIV self-testing (HIVST) can increase uptake, but users' perspectives on optimal models of distribution and post-test services are uncertain. We used discrete choice experiments (DCEs) to explore the impact of service characteristics on uptake along the testing cascade. Methods: DCEs are a quantitative survey method that present respondents with repeated choices between packages of service characteristics, and estimate relative strengths of preferences for service characteristics. From June to October 2016, we embedded DCEs within a population-based survey following door-to-door HIVST distribution by community volunteers in two rural Zimbabwean districts: one DCE addressed HIVST distribution preferences; and the other preferences for linkage to confirmatory testing (LCT) following self-testing. Using preference coefficients/utilities, we identified key drivers of uptake for each service and simulated the effect of changes of outreach and static/public clinics' characteristics on LCT. Results: Distribution and LCT DCEs surveyed 296/329 (90.0%) and 496/594 (83.5%) participants; 81.8% and 84.9% had ever-tested, respectively. The strongest distribution preferences were for: (1) free kits - a $1 increase in the kit price was associated with a disutility (U) of --2.017; (2) door-to-door kit delivery (U = +1.029) relative to collection from public/outreach clinic; (3) telephone helpline for pretest support relative to in-person or no support (U = +0.415); (4) distributors from own/local village (U = +0.145) versus those from external communities. Participants who had never HIV tested valued phone helpines more than those previously tested. The strongest LCT preferences were: (1) immediate antiretroviral therapy (ART) availability: U = +0.614 and U = +1.052 for public and outreach clinics, respectively; (2) free services: a $1 user fee increase decreased utility at public (U = -0.381) and outreach clinics (U = -0.761); (3) proximity of clinic (U = -0.38 per hour walking). Participants reported willingness to link to either location; but never-testers were more averse to LCT. Simulations showed the importance of availability of ART: ART unavailability at public clinics would reduce LCT by 24%. Conclusions: Free HIVST distribution by local volunteers and immediately available ART were the strongest relative preferences identified. Accommodating LCT preferences, notably ensuring efficient provision of ART, could facilitate 'resistant testers' to test while maximizing uptake of post-test services. Keywords: discrete choice experiments; HIV self-testing; HIV testing; Zimbabwe; HIV; preferences, 1 | INTRODUCTION HIV testing is an important entry point for uptake of prevention, treatment and care services. The United Nations 90-90-90 targets are that by 2020, 90% of people [...]

Introduction: Scale-up of HIV self-testing (HIVST) will play a key role in meeting the United Nation's 90-90-90 targets. Delayed re-reading of used HIVST devices has been used by early implementation studies to validate the performance of self-test kits and to estimate HIV positivity among self-testers. We investigated the stability of results on used devices under controlled conditions to assess its potential as a quality assurance approach for HIVST scale-up. Methods: 444 OraQuick[R] HIV-1/2 rapid antibody tests were conducted using commercial plasma from two HIV-positive donors and HIV-negative plasma (high-reactive n = 148, weak-reactive n = 148 and non-reactive n = 148) and incubated them for six months under four conditions (combinations of high and low temperatures and humidity). Devices were reread daily for one week, weekly for one subsequent month and then once a month by independent readers unaware of the previous results. We used multistage transition models to investigate rates of change in device results, and between storage conditions. Results and discussion: There was a high incidence of device instability. Forty-three (29%) of 148 initially non-reactive results became false weak-reactive results. These changes were observed across all incubation conditions, the earliest on Day 4 (n = 9 kits). No initially HIV-reactive results changed to a non-reactive result. There were no significant associations between storage conditions and hazard of results transition. We observed substantial statistical agreement between independent re-readers over time (agreement range: 0.74 to 0.96). Conclusions: Delayed re-reading of used OraQuick[R] HIV-1/2 rapid antibody tests is not currently a valid methodologica approach to quality assurance and monitoring as we observed a high incidence (29%) of true non-reactive tests changing to false weak-reactive and therefore its use may overestimate true HIV positivity. Keywords: HIV self-testing; Quality assurance; Delayed re-reading; Visual stability; False reactive; Misdiagnosis; HIV testing, 1 | INTRODUCTION HIV self-testing (HIVST) is being scaled-up using a variety of distribution models throughout Africa, the Americas, Asia and Europe [1-4]. No clear monitoring and evaluation or external [...]

Introduction: HIV self-testing (HIVST) is being introduced as a new way for more undiagnosed people to know their HIV status. As countries start to implement HIVST, assuring the quality and regulating in vitro diagnostics, including HIVST, are essential. We aimed to document the emerging regulatory landscape and perceptions of key stakeholders involved in HIVST policy and regulation prior to implementation in three low- and middle-income countries. Methods: Between April and August 2016, we conducted semi-structured interviews in Malawi, Zambia and Zimbabwe to understand the relationships between different stakeholders on their perceptions of current and future HIVST regulation and the potential impact on implementation. We purposively sampled and interviewed 66 national-level key stakeholders from the Ministry of Health and the regulatory, laboratory, logistical, donor and non-governmental sectors. We used a thematic approach to analysis with an inductively developed common coding framework to allow inter-country comparison of emerging themes. Results: In all countries, the national reference laboratory was monitoring the quality of HIVST kits entering the public sector. In Malawi, there was no legal mandate to regulate medical devices, in Zambia one regulatory body with a clear mandate had started developing regulations and in Zimbabwe the mandate to regulate was overlapping between two bodies. Stakeholders indicated that they had a poor understanding of the process and requirements for HIVST regulation, as well as lack of clarity and coordination between organizational roles. The need for good collaboration between sectors, a strong post-market surveilance model for HIVST and technical assistance to develop regulators capacity was noted as priorities. Key informants identified technical working groups as a potential way collaboration could be improved upon to accelerate the regulation of HIVST. Conclusion: Regulation of in vitro diagnostic devices, including HIVST, is now being recognized as important by regulators after a regional focus on pharmaceuticals. HIVST is providing an opportunity for each country to develop similar regulations to others in the region leading to a more coherent regulatory environment for the introduction of new devices. Keywords: quality assurance; policy; in vitro diagnostics; post market; implementation; harmonization, 1 | INTRODUCTION The World Health Organization (WHO) defines HIV self-testing (HIVST) as 'a process in which a person collects his or her own specimen (oral fluid or blood) and [...]

Introduction: The ability to achieve an accurate test result and interpret it correctly is critical to the impact and effectiveness of HIV self-testing (HIVST). Simple and easy-to-use devices, instructions for use (IFU) and other support tools have been shown to be key to good performance in sub-Saharan Africa and may be highly contextual. The objective of this study was to explore the utility of cognitive interviewing in optimizing the local understanding of manufacturers' IFUs to achieve an accurate HIVST result. Methods: Functionally literate and antiretroviral therapy-naive participants were purposefully selected between May 2016 and June 2017 to represent intended users of HIV self-tests from urban and rural areas in Malawi and Zambia. Participants were asked to follow IFUs for HIVST. We then conducted cognitive interviews and observed participants while they attempted to complete the HIVST steps using a structured guide, which mirrored the steps in the IFU. Qualitative data were analysed using a thematic approach. Results: Of a total of 61 participants, many successfully performed most steps in the IFU. Some had difficulties in understanding these and made errors, which could have led to incorrect test results, such as incorrect use of buffer and reading the results prematurely. Participants with lower levels of literacy and inexperience with standard pictorial images were more likely to struggle with IFUs. Difficulties tended to be more pronounced among those in rural settings. Ambiguous terms and translations in the IFU, unfamiliar images and symbols, and unclear order of the steps to be followed were most commonly linked to errors and lower comprehension among participants. Feedback was provided to the manufacturer on the findings, which resulted in further optimization of IFUs. Conclusions: Cognitive interviewing identifies local difficulties in conducting HIVST from manufacturer-translated IFUs. It is a useful and practical methodology to optimize IFUs and make them more understandable. Keywords: HIV self-test; performance; in vitro diagnosis; instructions for use; Zambia; Malawi, 1 | INTRODUCTION HIV self-testing (HIVST) is increasingly being introduced as a testing approach recommended by the World Health Organization (WHO) to reach those who may not otherwise test [1,2]. [...]

: Background: HIV and tuberculosis are frequently diagnosed concurrently. In March 2021, World Health Organization recommended that antiretroviral therapy (ART) should be started within two weeks of tuberculosis treatment start, at any CD4 count. We assessed whether earlier ART improved outcomes in people with newly diagnosed HIV and tuberculosis. Methods: We did a systematic review by searching nine databases for trials that compared earlier ART to later ART initiation in people with HIV and tuberculosis. We included studies published from database inception to 12 March 2021. We compared ART within four weeks versus ART more than four weeks after TB treatment, and ART within two weeks versus ART between two and eight weeks, and stratified analysis by CD4 count. The main outcome was death; secondary outcomes included IRIS and AIDS‐defining events. We pooled effect estimates using random effects meta‐analysis. Results and discussion: We screened 2468 abstracts, and identified nine trials. Among people with all CD4 counts, there was no difference in mortality by earlier ART (≤4 week) versus later ART (>4 week) (risk difference [RD] 0%, 95% confidence interval [CI] −2% to +1%). Among people with CD4 count ≤50 cells/mm[sup.3], earlier ART (≤4 weeks) reduced risk of death (RD −6%, −10% to −1%). Among people with all CD4 counts earlier ART (≤4 weeks) increased the risk of IRIS (RD +6%, 95% CI +2% to +10%) and reduced the incidence of AIDS‐defining events (RD −2%, 95% CI −4% to 0%). Results were similar when trials were restricted to the four trials which permitted comparison of ART within two weeks to ART between two and eight weeks. Trials were conducted between 2004 and 2014, before recommendations to treat HIV at any CD4 count or to rapidly start ART in people without TB. No trials included children or pregnant women. No trials included integrase inhibitors in ART regimens. Discussion: Earlier ART did not alter risk of death overall among people living with HIV who had TB disease. For logistical and patient preference reasons, earlier ART initiation for everyone with TB and HIV may be preferred to later ART., Introduction Tuberculosis (TB) is the most important cause of morbidity and mortality among people living with HIV (PLHIV) globally [1,2]. All people with TB should be offered testing for HIV [...]

Introduction: HIV and tuberculosis (TB) remain leading causes of preventable death in low- and middle-income countries (LMICs). The World Health Organization (WHO) recommends HIV testing for all individuals with TB symptoms, but implementation has been suboptimal. We conducted a systematic literature review and meta-analyses to estimate HIV and TB prevalence, and short-term (two to six months) mortality, among adults with TB symptoms at community- and facility level. Methods: We searched Embase, Global Health and MEDLINE databases, and reviewed conference abstracts for studies reporting simultaneous HIV and TB screening of adults in LMICs published between January 2003 and December 2017. Meta-analyses were performed to estimate prevalence of HIV, undiagnosed TB and mortality risk at different health system eve Is. Results: Sixty-two studies including 260,792 symptomatic adults were identified, mostly from Africa and Asia. Median HIV prevalence was 19.2% (IQR: 8.3% to 40.4%) at community level, 55.7% (IQR: 20.9% to 71.2%) at primary care level and 80.7% (IQR: 73.8% to 84.6%) at hospital level. Median TB prevalence was 6.9% (IQR: 3.3% to 8.4%) at community, 20.5% (IQR: 11.7% to 46.4%) at primary care and 36.4% (IQR: 22.9% to 40.9%) at hospital level. Median short-term mortality was 22.6% (IQR: 15.6% to 27.7%) among inpatients, 3.1% (IQR: 1.2% to 4.2%) at primary care and 1.6% (95% CI: 0.45 to 4.13, n = 1 study) at community level. Conclusions: Adults with TB symptoms have extremely high prevalence of HIV infection, even when identified through community surveys. TB prevalence and mortality increased substantially at primary care and inpatient level respectively. Strategies to expand symptom-based TB screening combined with HIV and TB testing for all symptomatic individuals should be of the highest priority for both disease programmes in LMICs with generalized HIV epidemics. Interventions to reduce short-term mortality are urgently needed. Keywords: Tuberculosis; HIV; screening; mortality; policy; health systems, 1 | INTRODUCTION Tuberculosis (TB) and human immunodeficiency virus (HIV) are the two leading causes of adult infectious disease deaths worldwide. In 2016, there were 1.7 million deaths due to [...]

: Introduction: Strategies employing a single rapid diagnostic test (RDT) such as HIV self‐testing (HIVST) or “test for triage” (T4T) are proposed to increase HIV testing programme impact. Current guidelines recommend serial testing with two or three RDTs for HIV diagnosis, followed by retesting with the same algorithm to verify HIV‐positive status before anti‐retroviral therapy (ART) initiation. We investigated whether clients presenting to HIV testing services (HTS) following a single reactive RDT must undergo the diagnostic algorithm twice to diagnose and verify HIV‐positive status, or whether a diagnosis with the setting‐specific algorithm is adequate for ART initiation. Methods: We calculated (1) expected number of false‐positive (FP) misclassifications per 10,000 HIV negative persons tested, (2) positive predictive value (PPV) of the overall HIV testing strategy compared to the WHO recommended PPV ≥99%, and (3) expected cost per FP misclassified person identified by additional verification testing in a typical low‐/middle‐income setting, compared to the expected lifetime ART cost of $3000. Scenarios considered were as follows: 10% prevalence using two serial RDTs for diagnosis, 1% prevalence using three serial RDTs, and calibration using programmatic data from Malawi in 2017 where the proportion of people testing HIV positive in facilities was 4%. Results: In the 10% HIV prevalence setting with a triage test, the expected number of FP misclassifications was 0.86 per 10,000 tested without verification testing and the PPV was 99.9%. In the 1% prevalence setting, expected FP misclassifications were 0.19 with 99.8% PPV, and in the Malawi 2017 calibrated setting the expected misclassifications were 0.08 with 99.98% PPV. The cost per FP identified by verification testing was $5879, $3770, and $24,259 respectively. Results were sensitive to assumptions about accuracy of self‐reported reactive results and whether reactive triage test results influenced biased interpretation of subsequent RDT results by the HTS provider. Conclusions: Diagnosis with the full algorithm following presentation with a reactive triage test is expected to achieve PPV above the 99% threshold. Continuing verification testing prior to ART initiation remains recommended, but HIV testing strategies involving HIVST and T4T may provide opportunities to maintain quality while increasing efficiency as part of broader restructuring of HIV testing service delivery., Introduction Substantial scale‐up of HIV testing services (HTS) has contributed to tremendous progress towards global targets to diagnose 90% of people with HIV by 2020. In 2017, PEPFAR alone conducted [...]

Pre-treatment loss to follow-up in tuberculosis patients in low- and lower-middle-income countries and high-burden countries: a systematic review and meta-analysis/Le manque de suivi avant le traitement chez les patients atteints de tuberculose dans les pays a revenu faible et a revenu moyen inferieur fortement touches par la maladie: meta-analyse et analyse systematique/ Perdida de seguimiento antes del tratamiento de pacientes con tuberculosis en paises de ingresos medios y bajos y en paises con carga alta: una revision sistematica y metanalisis. Objective To assess the magnitude of loss to follow-up in smear- or culture-positive tuberculosis patients before treatment initiation and outcomes among patients who were traced. Methods Ovid Medline and Global Health databases were searched for studies published between 1994 and January 2013 that described pre-treatment loss to follow-up in patients with smear- or culture-positive tuberculosis in routine national tuberculosis programmes (NTPs) in low- and lower-middle-income countries and in countries with a high burden of tuberculosis. Data on the proportion of patients who did not initiate treatment after their tuberculosis diagnosis were extracted from studies meeting inclusion criteria. Where available, data on causes and outcomes, including initiation of tuberculosis treatment at another facility, were investigated. Heterogeneity and publication bias were assessed and random-effects meta-analyses by subgroup (region) were performed. Findings Twenty-three eligible studies were identified, with a total of 34 706 smear- or culture-positive tuberculosis patients from 14 countries (8 in Africa, 5 in Asia and I in the western Pacific). Most studies were retrospective and linked laboratory and treatment registers to identify pre-treatment loss to follow-up. Pre-treatment loss to follow-up varied from 4 to 38% and was common in studies from Africa (random-effects weighted proportion, WP: 18%; 9.5% confidence interval, CI: 13-22) and Asia (WP: 13%; 95% CI: 10-15). Conclusion Pre-treatment loss to follow-up, common in most settings, can hinder tuberculosis control efforts. By not counting individuals who are lost to follow-up before treatment when reporting standard programme indicators, NTPs underestimate case detection rates and mortality and overestimate cure rates. Objectif Evaluer I'ampleur du manque de suivi chez les patients atteints d'une tuberculose a frottis positif ou culture positive avant le debut du traitement, ainsi que les resultats chez les patients qui ont ete suivis. Methodes Des etudes publiees entre 1994 etjanvier 2013, qui decrivaient le manque de suivi des patients atteints de tuberculose a frottis positif ou a culture positive dans des programmes nationaux courants de lutte contre la tuberculose (NTP) dans les pays a revenu faible et a revenu moyen inferieur fortement touches par la tuberculose ont ete recherchees dans les bases de donnees Ovid, Medline et Global Health. Des donnees concernant le taux de patients qui n'ont pas debute le traitement apres leur diagnostic de tuberculose ont ete extraites des etudes satisfaisant les criteres d'inclusion. Le cas echea nt, les donnees portant sur les causes et les resultats, y compris le debut d'un traitement contre la tuberculose dans un autre etablissement, ont ete examinees. L'heterogeneite et le parti pris dans les publications ont ete evalues, et des meta-analyses a effets aleatoires par sous-groupe (region) ont ete realisees. Resultats Vingt-trois etudes eligibles ont ete identifiees pour un total de 34 706 patients atteints de tuberculose a frottis positif ou a culture positive dans 14 pays (8 en Afrique, 5 en Asie et 1 dans le Pacifique occidental). La plupart des etudes etaient retrospectives et associaient des registres de laboratoire et de traitement pour identifier le manque de suivi avant le traitement. Celui-ci variait de 4% a 38% et s'est revele commun dans les etudes provenant d'Afrique (proportion ponderee a effets aleatoires, PP: 18%; intervalle de confiance a 95%, IC: 13-22) et d'Asie (PP: 13%; IC a 95%: 10-15). Conclusion Le manque de suivi avant le traitement, commun dans la plupart des contextes, peut entraver les efforts fournis en matiere de lutte contre la tuberculose. Comme les individus qui ne sont pas suivis avant le traitement ne sont pas pris en compre Iors de I'elaboration des rapports sur les indicateurs de programme standard, les programmes nationaux de lutte contre la tuberculose sous-estiment les taux de depistage des caset la mortalite, mais surestiment les taux de guerison. Objetivo Evaluar la magnitud de la perdida de seguimiento de los pacientes con tuberculosis que dieron positivo en el analisis o el cultivo antes del inicio del tratamiento y los resultados entre los pacientes que se sometieron a un seguimiento. Metodos Se realizo una busqueda en las bases de datos Ovid, Medline y Global Health deestudios publicados entre 1994y enerode 2013 que describian perdidas de seguimiento antes del tratamiento en pacientes que dieron positivo en el analisis o el cultivo de tuberculosis en los programas nacionales contra la tuberculosis (PNT) ordinarios en paises de ingresos medios y baios y en paises con carga alta de tuberculosis. Se extrajeron datos sobre la proporcion de pacientes que no inicio un tratamiento despues del diagnostico de la tuberculosis de estudios que cumplian los criterios de inclusion. Siempre que fue posible, se investigaron los datos sobre las causas y resultados, incluida la iniciadon del tratamiento de la tuberculosis en otro centro. Se evaluo el sesgo de las publicaciones y la heterogeneidad, y se realizaron metanalisis de erectos aleatorios por subgrupos (region). Resultados Se identificaron veintitres estudios que cumplian los criterios, con un total de 34 706 pacientes que dieron positivo enel analisis o cultivo de tuberculosis de 14 paises (8 de Africa, 5 de Asia y 1 del Pacifico occidental). La mayoria de los estudios eran retrospectivos y relacionaban los registros de laboratorio con los registros de tratamiento para identificar la perdida de seguimiento antes del tratamiento, que oscilo entre el 4 y 38% y fue frecuente en los estudios de Africa (proporcion ponderada de erectos aleatorios, WP: 18%; intervalo de confianza del 95%, IC: 13-22) y Asia (WP: 13%; IC del 95%: 10-15). Conclusion La perdida de seguimiento antes del tratamiento, comun en la mayoria de los entornos, puede obstaculizar los esfuerzos de control de la tuberculosis. Sin contar los pacientes cuyo seguimiento se pierde antes del tratamiento, los programas nacionales contra la tuberculosis subestiman la mortalidad y las tasas de deteccion de casos, a la vez que sobrestiman las rasas de curacion ai informar sobre los indicadores del programa estandar., Introduction Since tuberculosis was declared a global emergency in 1993 by the World Health Organization (WHO), new cases of tuberculosis and deaths from the disease have dropped dramatically in several [...]

Objective To establish the proportion d adolescents among children infected with human immunodeficiency virus (HIV) in Zimbabwe who receive HIV care and support, and what clinic staff perceives to be the main problems faced by HIV-infected children and adolescents. Methods In July 2008, we sent a questionnaire to all 131 facilities providing HIV care in Zimbabwe. In it we requested an age breakdown of the children (aged 0-19 years) registered for care and asked what were the two major problems faced by younger children (0-5 years) and adolescents (10-19 years). Findings Nationally, 115 (88%) facilities responded. In 98 (75%) that provided complete data, 196 032 patients were registered and 24 958 (13%) of them were children. Of children under HIV care, 33% were aged 0-4 years; 25%, 5-9 years; 25%, 10-14 years; and 17%, 15-19 years. Staff highlighted differences in the problems most commonly faced by younger children and adolescents. For younger children, such problems were malnutrition and lack of appropriate drugs (cited by 46% and 40% of clinics, respectively); for adolescents they concerned psychosocial issues and poor drug adherence (cited by 56% and 36%, respectively). Conclusion Interventions for the large cohort of adolescents who are receiving HIV care in Zimbabwe need to target the psychosocial concerns and poor drug adherence reported by staff as being the main concerns in this age group. Une traduction en francais de ce resume figure a la fin de I'article. AI final del articulo se facilita una traduccion al espanol. Objectif Determiner la proportion d'adolescents parmi les enfants infectes par le virus de I'immunodeficience humaine (VIH) au Zimbabwe recevant des soins et un soutien en rapport avec le VIH et ce que le personnel des dispensaires percoit comme les principaux problemes rencontres par les enfants et les adolescents infectes par ce virus. Methodes En juillet 2008, nous avons envoye un questionnaire a I'ensemble des 131 etablissements delivrant des soins lies au VIH au Zimbabwe. II etait demande dans ce questionnaire de classer par age les enfants (0-19 ans) enregistres pour recevoir des soins et d'indiquer les deux principaux problemes se posant pour les plus jeunes (0-5 ans) et pour les adolescents (10-19 ans). Resultats A I'echelle du pays, 115 (88 %) etablissements ont repondu. Dans 98 etablissements (75 %) ayant fourni des donnees completes, 196 032 patients ont ete enregistres, dont 24 958 (13 %) enfants. Parmi les enfants soignes contre le VIH/sida, 33 % etaient ages de O a 4 ans, 25% de 5 a 9 ans, 25 % de 10 a 14 ans et 17 % de 15 a 19 ans. Le personnel a mis en lumiere des differences entre les problemes qui se posaient le plus frequemment pour les jeunes enfants et pour les adolescents. Pour les plus jeunes, ces problemes concernaient la malnutrition et le manque de medicaments adaptes (cites par 46 et 40 % des dispensaires respectivement) ; pour les adolescents, li s'agissait plutot de problemes psychosociaux et d'une mauvaise observance du traitement (cites par 56 et 36 % des dispensaires respectivement). Conclusion Les interventions destinees a I'importante cohorte d'adolescents qui recoit des soins lies au VlH au Zimbabwe doivent viser les difficultes psychosociales et les defauts d'observance du traitement rapportes par le personnel en tant que problemes les plus preoccupants dans cette tranche d'ages. Objetivo Determinar la proporcion de adolescentes que reciben atencion y apoyo contra el VIH entre los ninos infectados por el virus de la inmunodeficiencia humana (VlH) en Zimbabwe, asi como los principales problemas que, en opinion del personal de los dispensarios, afrontan los ninos y adolescentes infectados por el virus. Metodos En julio de 2008 enviamos un cuestionario a los 131 centros que atienden a pacientes con VIH en Zimbabwe. En el solicitamos un desglose por edades de los ninos (de O a 19 anos) registrados para recibir atencion y preguntamos cuales eran los dos problemas que mas afectaban a los ninos mas pequenos (0-5 anos) y a los adolescentes (10-19 anos). Resultados A nivel nacional, respondieron en total 115 centros (88%). En 98 (75%) que proporcionaron datos completos, habia registrados 196 032 pacientes, 24 958 (13%) de los cuales eran ninos. De los ninos atendidos por ser seropositivos, el 33% tenian entre O y 4 anos; el 25%, 5-9 anos, otro 25%, 10-14 anos; y el 17%, 15-19 anos. EI personal resalto las diferencias entre los problemas mas comunes sufridos por los ninos mas pequenos y los que afectaban a los adolescentes. Ente los primeros cabe destacar la malnutricion y la falta de medicamentos apropiados (citados por el 46% y el 40% de los dispensarios, respectivamente); y en el caso de los adolescentes, los problemas psicosociales y el escaso seguimiento de la medicacion (citados por el 56% y el 36%, respectivamente). Conclusion En las intervenciones aplicadas en la extensa cohorte de adolescentes que estan recibiendo atencion para el VlH en Zimbabwe se deberia centrar la atencion en los aspectos psicosociales y el cumplimiento del tratamiento, cuestiones identificadas por el personal como los principales motivos de preocupacion en ese grupo de edad., Introduction Infection with human immunodeficiency virus (HIV) is the leading cause of death in southern Africa, which has the highest prevalence of HIV infection in the world. (1) Without interventions, [...]

Objective To assess the diagnostic value of provider-initiated symptom screening for tuberculosis (TB) and how HIV status affects it. Methods We performed a secondary analysis of randomly selected participants in a community-based TB-HIV prevalence survey in Harare, Zimbabwe. All completed a five-symptom questionnaire and underwent sputum TB culture and HIV testing. We calculated the sensitivity, specificity, and positive and negative predictive values of various symptoms and used regression analysis to investigate the relationship between symptoms and TB disease. Findings We found one or more symptoms of TB in 21.2% of 1858 HIV-positive (HIV+) and 9.9% of 7121 HIV-negative (HIV-) participants (P < 0 .001). TB was subsequently diagnosed in 48 HIV+ and 31 HIV-participants. TB was asymptomatic in 18 culture-positive individuals, 8 of whom (4 in each HIV status group) had positive sputum smears. Cough of any duration, weight loss and, for HIV+ participants only, drenching night sweats were independent predictors of TB. In HIV+ participants, cough of ≥ 2 weeks' duration, any symptom and a positive sputum culture had sensitivities of 48%, 81% and 65%, respectively; in HIV--participants, the sensitivities were 45%, 71% and 74%; respectively. Symptoms had a similar sensitivity and specificity in HIV+ and HIV- participants, but in HIV+ participants they had a higher positive and a lower negative predictive value. Conclusion Even smear-positive TB may be missed by provider-initiated symptom screening, especially in HIV+ individuals. Symptom screening is useful for ruling out TB, but better TB diagnostics are urgently needed for resource-poor settings. Objectif Evaluer la valeur diagnostique de la recherche des symptomes de la tuberculose (TB) a l'initiative du prestateur et comment le statut VIH influe sur cette valeur diagnostique. Methodes Nous avons realise une analyse secondaire sur des participants selectionnes au hasard parmi les sujets d'une enquete en communaute concernant la prevalence de la co-infection TB-VIH, menee a Harare, au Zimbabwe. Tous les participants ont repondu a un questionnaire portant sur cinq symptomes et ont fait l'objet d'une culture d'expectorations pour rechercher la tuberculose et d'un depistage du VIH. Nous avons calcule la sensibilite, la specificite et les valeurs predictives positive et negative des differents symptomes et etudie la relation entre ces symptomes et la tuberculose maladie en utilisant l'analyse par regression. Resultats Nous avons releve un ou plusieurs symptomes de la tuberculose chez 21,2 % des 1858 participants positifs pour le VIH (VIH+) et chez 9,9 % des 7121 participants negatifs pour ce virus (p < 0,001). La tuberculose a ensuite ete diagnostiquee chez 48 sujets VIH+ et chez 31 sujets VIH-. Cette maladie etait presente de maniere asymptomatique chez 18 individus positifs a la culture, dont 8 (4 pour chacun des statuts VIH) donnaient ales frottis d'expectorations positifs. La toux, quelle que soit sa duree, la perte de poids et pour les participants VIH+ uniquement, la sudation nocturne, constituaient des facteurs predictifs independants de la tuberculose. Chez les participants VIH+, la presence de toux pendant 2 semaines ou plus, chacun des symptomes et l'obtention d'une culture d'expectorations positive presentaient respectivement une sensibilite de 48, 81 et 65 %. Chez les participants VIH-, les sensibilites correspondantes valaient respectivement 45, 71 et 74 %. Les symptomes fournissaient donc une sensibilite et une specificite similaires chez les deux types de participants, mais chez les sujets VIH+, ils avaient une valeur predictive positive plus elevee et une valeur predictive negative plus faible. Conclusion La recherche des symptomes a l'initiative du prestateur peut laisser passer meme ales cas de tuberculose frottis positifs, en particulier chez les individus seropositifs pour le VIH. Le depistage sur la base des symptomes est utile pour exclure la tuberculose, mais les pays demunis ont besoin d'urgence d'un meilleur outil pour diagnostiquer cette maladie. Objetivo Determinar el valor diagnostico del cribado de sintomas de tuberculosis a instancias del profesional, asi como la influencia de la serologia VIH en dicho cribado. Metodos Realizamos un analisis secundario a partir de participantes seleccionados aleatoriamente en una encuesta comunitaria de prevalencia de la coinfeccion tuberculosis-VIH realizada en Harare, Zimbabwe. Todos ellos respondieron a un cuestionario sobre cinco sintomas y se sometieron a pruebas del VIH y de cultivo de esputo para la tuberculosis. Calculamos la sensibilidad, la especificidad y los valores predictivos positivo y negativo de Ios diversos sintomas y realizamos un analisis de regresion para investigar la relacion entre Ios sintomas y la tuberculosis. Resultados Detectamos uno o mas sintomas de tuberculosis en el 21,2% de 1858 pacientes VIH-positivos (VIH+) y el 9,9% de 7121 participantes VIH-negativos (VIH-) (p < 0,001). Posteriormente se diagnostico tuberculosis en 48 participantes VIH+ y 31 participantes VIH-. Sufrian tuberculosis asintomatica 18 personas con cultivo positivo, 8 de las cuales (4 en cada grupo serologico) presentaron esputo positivo. La tos de cualquier duracion, la perdida de peso y, solo en el caso de Ios participantes VIH+, la presencia de sudores nocturnos, fueron factores predictivos independientes de la tuberculosis. En las personas VIH+, la tos de mas de 2 semanas de duracion, la presencia de cualquiera de los sintomas y un cultivo de esputo positivo tuvieron una sensibilidad del 48%, 81% y 65%, respectivamente; entre los participantes VIH-, la sensibilidad fue del 45%, 71% y 74%, respectivamente. Los sintomas presentaron una sensibilidad y especificidad similares en Ios pacientes VIH+ y VIH-, pero en los primeros tenian un mayor valor predictivo positivo y un menor valor predictivo negativo. Conclusion Incluso la tuberculosis con baciloscopia positiva puede pasar desapercibida en el cribado de Ios sintomas realizado a instancias del profesional, especialmente en las personas VIH+. El cribado de los sintomas es util para descartar la tuberculosis, pero se necesitan urgentemente mejores medios de diagnostico de esta enfermedad para Ios entornos con recursos escasos., Introduction Symptom questionnaires provide a quick, cheap and convenient way to identify individuals at a high risk of tuberculosis (TB) disease, termed TB suspects, who then need investigation with more [...]

Introduction: The World Health Organization (WHO) recommends that HIV‐positive adults with CD4 count ≤500 cells/mm[sup.3] initiate antiretroviral therapy (ART). In many countries of sub‐Saharan Africa, CD4 count is not widely available or consistently used and instead the WHO clinical staging system is used to determine ART eligibility. However, concerns have been raised regarding its discriminatory ability to identify patients eligible to start ART. We therefore reviewed the accuracy of WHO stage 3 or 4 assessment in identifying ART eligibility according to CD4 count thresholds for ART initiation. Methods: We systematically searched PubMed and Global Health databases and conference abstracts using a comprehensive strategy for studies that compared the results of WHO clinical staging with CD4 count thresholds. Studies performed in sub‐Saharan Africa and published in English between 1998 and 2013 were eligible for inclusion according to our predefined study protocol. Two authors independently extracted data and assessed methodological quality and risk of bias using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS‐2) tool. Summary estimates of sensitivity and specificity were derived for each CD4 count threshold and hierarchical summary receiver operator characteristic curves were plotted. Results: Fifteen studies met the inclusion criteria, including 25,032 participants from 14 countries. Most studies assessed individuals attending ART clinics prior to treatment initiation. WHO clinical stage 3 or 4 disease had a sensitivity of 60% (95% CI: 45–73%, Q=914.26, p Conclusions: When used for individual treatment decisions, WHO clinical staging misses a high proportion of individuals who are ART eligible by CD4 count, with sensitivity falling as CD4 count criteria rises. Access to accurate, accessible, robust and affordable CD4 count testing methods will be a pressing need for as long as ART initiation decisions are based on criteria other than seropositivity., Introduction At the end of 2012, an estimated 9.7 million HIV‐positive patients had initiated antiretroviral therapy (ART) worldwide, a 30‐fold increase since 2003 [1]. Despite this rapid scale‐up, 39% (under [...]

Introduction: Linkage from HIV testing and counselling (HTC) to initiation of antiretroviral therapy (ART) is suboptimal in many national programmes in sub‐Saharan Africa, leading to delayed initiation of ART and increased risk of death. Reasons for failure of linkage are poorly understood. Methods: Semi‐structured qualitative interviews were undertaken with health providers and HIV‐positive primary care patients as part of a prospective cohort study at primary health centres in Blantyre, Malawi. Patients successful and unsuccessful in linking to ART were included. Results: Progression through the HIV care pathway was strongly influenced by socio‐cultural norms, particularly around the perceived need to regain respect lost during a period of visibly declining health. Capacity to call upon the support of networks of families, friends and employers was a key determinant of successful progression. Over‐busy clinics, non‐functioning laboratories and unsuitable tools used for ART eligibility assessment (WHO clinical staging system and centralized CD4 count measurement) were important health systems determinants of drop‐out. Conclusions: Key interventions that could rapidly improve linkage include guarantee of same‐day, same‐clinic ART eligibility assessments; utilization of the support offered by peer‐groups and community health workers; and integration of HTC and ART programmes., Introduction Despite being one of the poorest countries in the world [1], with an HIV prevalence of 11% [1], Malawi has made impressive achievements in scaling up provision of HIV [...]

A comprehensive and up-to-date review of the treatment of patients coinfected with HIV and tuberculosis is provided. A scientific foundation for the devising management strategies for tuberculosis/HIV, in resource-poor settings, is discussed.

Human immunodeficiency virus (HIV) increases the risks of developing tuberculosis (TB) disease following infection, and speeds up disease progression. This has had a devastating effect on TB epidemics in sub-Saharan Africa, where incidence rates have more than trebled in the past twenty years. Current control methods for TB disease have failed to keep pace with this growth, and there is an urgent need to find TB control strategies that are effective in high-HIV prevalent settings. This article describes a discrete-event simulation model of endemic TB that includes the effects of HIV and of household structure on the transmission dynamics of TB. Incorporating a social structure allows us to compare the effectiveness of contact-tracing interventions with case-finding targeted at high risk groups. We describe the modeling of the household structure in some detail, as this has applications to the modeling of other infectious diseases. [ABSTRACT FROM AUTHOR]