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test the safety and efficacy of this new formulation in young children

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Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

The challenge

Sexually transmitted infections (STIs) are a major challenge in sub-Saharan Africa. As well as their direct impact, they can also increase the risk of HIV infection, while HIV can increase the risk of other STIs. In Rwanda, for example, almost 1% of HIV-negative women but nearly 5% of HIV-positive women are infected with syphilis, and certain groups are particularly vulnerable to infection.

In most low-resource settings, including Rwanda, STIs are treated though syndromic management. Treatment is based on clinician assessment of symptoms, without confirmatory diagnosis. Although simple, this can lead to both over-treatment, use of antibiotics that are not needed, and under-treatment. In women, under-treatment is a particular challenge as most STIs are asymptomatic but can have multiple long-term health consequences.

Since 2004, the Rinda Ubuzima NGO in Kigali, Rwanda, has operated a research clinic and laboratory specialising in women’s sexual and reproductive health. Rinda Ubuzima has hosted several EDCTP projects.

The WISH project took advantage of this newly established research capacity to explore the potential for improved diagnosis and management of STIs in women. An increasing number of point-of-care diagnostic tests are now available for key STIs, including HIV, Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, syphilis and bacterial vaginosis (disruptions to vaginal bacterial ecosystems).

The WISH project recruited 705 women from the community at risk of STIs, who were assessed by standard WHO approaches to diagnosis and specially developed WISH algorithms. Participants were also tested for T. vaginalis and bacterial vaginosis, and high-risk women were additionally screened for N. gonorrhoeae and Chlamydia. All samples underwent gold standard laboratory testing.

The results revealed that the prevalence of urogenital infections was high in the study population. Rwandan and WHO syndromic algorithms performed poorly, illustrating that reported symptoms and signs do not reliably predict the presence of urogenital infections. The performance of WISH algorithms was significantly better, although improved point-of-care tests are needed, particularly for vaginosis and candidiasis. Testing was also acceptable to both service providers and users.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The results were shared with policymakers at a workshop in Rwanda. The consensus was that use of diagnostic testing was desirable, programmatically feasible and acceptable to communities. However, the costs of diagnostic tests remain a significant obstacle to implementation.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact