ArticlesCryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: an open-label, randomised controlled trial
Introduction
About 10 million people in Africa are now receiving antiretroviral therapy (ART) for the treatment of HIV infection. Mortality in Africans during the first year of ART is higher than in Europeans, particularly during the first few months of treatment.1 Additionally, in Africa, mortality2, 3 and loss to follow-up4 are high during the pretreatment period between a patient's first presentation to clinic and ART initiation. About a third of Africans still begin ART with advanced disease,5, 6 and have a very high disease burden.
Tuberculosis and cryptococcal meningitis account for most deaths in people with HIV infection presenting at health facilities in Africa.7, 8, 9 For tuberculosis, the median diagnostic delay is about 2 months overall10 and diagnosis in people co-infected with HIV presenting with advanced HIV disease is particularly challenging.11 In autopsy studies, tuberculosis has been detected in more than 50% of adults with HIV infection.12 Cryptococcal meningitis occurs mostly in individuals with a CD4 count of less than 100 cells per μL13 and is associated with 25–50% mortality in clinical trials and well functioning clinical settings.9, 14 The mortality associated with cryptococcal meningitis has remained high in some settings despite increased access to ART.15, 16
The biggest challenge facing health-care delivery in Africa is the severe shortage of qualified health-care workers, particularly doctors.17 Findings of a cluster-randomised trial18 showed that home-based care delivered by trained lay workers was as effective as standard clinic-based care in a predominately rural setting where access to clinics was difficult.
In this trial, we assessed the effect of a short period of community-based support provided to individuals with HIV infection who presented at health centres with advanced disease combined with screening for cryptococcal meningitis, compared with standard care.
Section snippets
Study design and participants
This study was an open-label, randomised controlled trial that took place in six public clinics serving urban and peri-urban populations: three in Dar es Salaam, Tanzania, and three in Lusaka, Zambia.
Recruitment began in February, 2012, when consecutive individuals with HIV infection were invited to join the trial if they were older than 18 years, presented with a CD4 count of less than 100 cells per μL, lived in the trial clinic catchment population, were able to communicate with staff, and
Results
Between Feb 9, 2012, and Sept 30, 2013, 26 (1%) of 3186 patients assessed for eligibility declined to join the trial and 1999 (63%) of 3186 were eligible and randomly assigned to either clinic plus community support (n=1001) or standard care (n=998; figure 1). Each participant was followed up for up to 12 months; and the last follow-up ended on Sept 30, 2014. 89 (9%) of 1001 participants in the clinic plus community support group did not receive the intervention (ie, a cryptococcal antigen
Discussion
In this trial, just four short home visits by lay workers to provide adherence support combined with screening for cryptococcal meningitis led to a significant reduction in mortality in patients infected with HIV starting ART with advanced disease. Mortality was about 30% less than in individuals who did not receive this simple supportive package. These findings were robust to sensitivity analyses. The trial was large, done under real-life conditions, had a low loss to follow-up, and the
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