HUMAN immunodeficiency virus (HIV) infection is a potent risk factor for tuberculosis (TB). Not only does HIV increase the risk of reactivating latent Mycobacterium tuberculosis (MTB) infection,¹ it also increases the risk of rapid TB progression soon after infection or reinfection with MTB.^2,3 In persons infected with MTB only, the lifetime risk of developing TB ranges between 10% and 20%.^4,5 In persons coinfected with MTB and HIV, however, the annual risk can exceed 10%.^1,6,7 The TB burden in countries with a generalized HIV epidemic has therefore increased rapidly over the past decade, especially in the severely affected countries of eastern and southern Africa.^8-12 Tuberculosis is one of the most common causes of morbidity and the most common cause of death in HIV-positive adults living in less-developed countries,^13-26 yet it is a preventable and treatable disease.

Smoking is the leading preventable cause of premature death in the United States. Previous studies of financial incentives for smoking cessation in work settings have not shown that such incentives have significant effects on cessation rates, but these studies have had limited power, and the incentives used may have been insufficient.

The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule. We identified 12 studies that had systematically collected sputum specimens regardless of signs or symptoms, at least one mycobacterial culture, clinical symptoms, and HIV and TB disease status. Bivariate random-effects meta-analysis and the hierarchical summary relative operating characteristic curves were used to evaluate the screening performance of all combinations of variables of interest. TB disease was diagnosed in 557 (5.8%) of 9,626 people living with HIV. The primary analysis included 8,148 people living with HIV who could be evaluated on five symptoms from nine of the 12 studies. The median age was 34 years. The best performing rule was the presence of any one of: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of this rule was 78.9% (95% confidence interval [CI] 58.3%–90.9%) and specificity was 49.6% (95% CI 29.2%–70.1%). Its sensitivity increased to 90.1% (95% CI 76.3%–96.2%) among participants selected from clinical settings and to 88.0% (95% CI 76.1%–94.4%) among those who were not previously screened for TB. Negative predictive value was 97.7% (95% CI 97.4%–98.0%) and 90.0% (95% CI 88.6%–91.3%) at 5% and 20% prevalence of TB among people living with HIV, respectively. Abnormal chest radiographic findings increased the sensitivity of the rule by 11.7% (90.6% versus 78.9%) with a reduction of specificity by 10.7% (49.6% versus 38.9%). Absence of all of current cough, fever, night sweats, and weight loss can identify a subset of people living with HIV who have a very low probability of having TB disease. A simplified screening rule using any one of these symptoms can be used in resource-constrained settings to identify people living with HIV in need of further diagnostic assessment for TB. Use of this algorithm should result in earlier TB diagnosis and treatment, and should allow for substantial scale-up of IPT. Please see later in the article for the Editors' Summary

Home-based HIV testing and counselling (HTC) achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST). The aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population. Following enumeration of 14 neighbourhoods in urban Blantyre, Malawi, trained resident volunteer-counsellors offered oral HIVST kits (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test) to adult (≥16 y old) residents (n = 16,660) and reported community events, with all deaths investigated by verbal autopsy. Written and demonstrated instructions, pre- and post-test counselling, and facilitated HIV care assessment were provided, with a request to return kits and a self-completed questionnaire. Accuracy, residency, and a study-imposed requirement to limit HIVST to one test per year were monitored by home visits in a systematic quality assurance (QA) sample. Overall, 14,004 (crude uptake 83.8%, revised to 76.5% to account for population turnover) residents self-tested during months 1–12, with adolescents (16–19 y) most likely to test. 10,614/14,004 (75.8%) participants shared results with volunteer-counsellors. Of 1,257 (11.8%) HIV-positive participants, 26.0% were already on antiretroviral therapy, and 524 (linkage 56.3%) newly accessed care with a median CD4 count of 250 cells/μl (interquartile range 159–426). HIVST uptake in months 13–24 was more rapid (70.9% uptake by 6 mo), with fewer (7.3%, 95% CI 6.8%–7.8%) positive participants. Being “forced to test”, usually by a main partner, was reported by 2.9% (95% CI 2.6%–3.2%) of 10,017 questionnaire respondents in months 1–12, but satisfaction with HIVST (94.4%) remained high. No HIVST-related partner violence or suicides were reported. HIVST and repeat HTC results agreed in 1,639/1,649 systematically selected (1 in 20) QA participants (99.4%), giving a sensitivity of 93.6% (95% CI 88.2%–97.0%) and a specificity of 99.9% (95% CI 99.6%–100%). Key limitations included use of aggregate data to report uptake of HIVST and being unable to adjust for population turnover. Community-based HIVST achieved high coverage in two successive years and was safe, accurate, and acceptable. Proactive HIVST strategies, supported and monitored by communities, could substantially complement existing approaches to providing early HIV diagnosis and periodic repeat testing to adolescents and adults in high-HIV settings. Every year, about 2.1 million people (70% of whom live in sub-Saharan Africa) are newly infected with HIV, the virus that causes AIDS, and 1.5 million people (again, mainly in sub-Saharan Africa) die as a result. HIV, which is usually transmitted through unprotected sex with an infected individual, gradually destroys CD4 lymphocytes and other immune system cells, leaving HIV-positive individuals susceptible to other serious infections and to unusual cancers. HIV is diagnosed by looking for antibodies to HIV in blood or saliva. After diagnosis, the progression of HIV infection is monitored by regularly counting the number of CD4 cells in the blood. Initiation of antiretroviral therapy—a combination of drugs that keeps HIV replication in check but that does not cure the infection—is recommended when an individual’s CD4 count falls below 500 cells/μl or when he or she develops an AIDS-defining condition. HIV-positive individuals need to know their status so that they can take steps to avoid transmitting the virus to other people (for example, by always using a condom during sexual intercourse) and so that they can begin treatment. Treatment helps to keep HIV-positive individuals healthy but also reduces their chances of transmitting the virus to their sexual partners. Unfortunately, many HIV-positive individuals are unaware of their status. The situation is particularly bad in sub-Saharan Africa, where, despite major investments in facility-based and community-based HIV testing and counseling (HTC) programs, only a quarter of adults have had a recent HIV test, and only half of the people living with HIV know they are HIV positive. Barriers to facility-based HTC include concern about lack of confidentiality and fears of stigmatization. Home-based HTC avoids some of these barriers and can achieve high uptake of testing, but doubts have been expressed about the sustainability of this approach to testing. Here, the researchers evaluate an alternative to home-based HTC—HIV self-testing (HIVST)—by undertaking a community-based prospective study of HIVST in Blantyre, Malawi. HIVST involves individuals performing and interpreting their own HIV test and has the potential to be widely implemented with minimal involvement of trained healthcare workers. Trained resident volunteer-counselors offered one oral HIVST kit (a kit that measures HIV in saliva) per year for a two-year period to 16,660 adult residents in 14 neighborhoods in urban Blantyre. All the participants received instructions on how to use the kits, pre- and post-counseling, and, for participants self-testing HIV positive, a referral card to attend an HIV care clinic. The residents also completed a questionnaire about their experience of HIVST. Three-quarters of the residents self-tested in the first and second year of the study. HIVST uptake was more rapid in the second year than in the first year and was high among men and adolescents, two hard-to-reach populations. Three-quarters of the residents who self-tested during the first year of the study shared their results with a volunteer-counselor. Of the 1,257 participants who discovered they were HIV positive during the first year of the study, more than half accessed HIV care. Importantly, 94.4% of the participants reported that they were happy with HIVST even though 2.9% reported being forced to take the test, usually by a main partner; no HIVST-related partner violence or suicides were reported by the study’s community surveillance system. Finally, HIVST and repeat HTC results agreed in 99.4% of participants selected as a quality assurance sample (one in 20 of the participants). These findings show that, in urban neighborhoods in Malawi, coverage with community-based HIVST was high (particularly among adolescents and men) in two successive years and that HIVST was safe, accurate, and acceptable. Importantly, HIVST using a delivery model based on trained volunteers led to acceptable linkage into HIV care services, and the approach had a very low incidence of major social harms such as partner violence. Uncertainty about estimates of uptake and linkage to care and other aspects of the study design may limit the accuracy of these results. Nevertheless, these findings suggest that scaling up HIVST could complement existing strategies for providing early HIV diagnosis and periodic repeat testing and could thus have a sustained impact on the coverage of HIV testing and care in Africa and on the control of the HIV/AIDS epidemic. This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001873.

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. 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). 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. Please see later in the article for the Editors' Summary