These are described in detail in the Methods section on page 477.
ReviewEffectiveness of antiretroviral therapy among HIV-infected children in sub-Saharan Africa
Introduction
Sub-Saharan Africa is the epicentre of the HIV pandemic and is home to an estimated 2 million HIV-infected children aged under 15 years, representing 90% of all HIV-infected children globally.1 Without treatment, more than one-third of these children will not survive past their first birthday.2 In 2003, WHO launched the 3 by 5 Initiative and mobilised resources to increase access to effective antiretroviral therapy in resource-poor settings to reduce morbidity and mortality caused by HIV. Substantial improvements have been made in sub-Saharan Africa for adults, with the estimated 100 000 people receiving antiretroviral therapy in 2003, increasing to more than 1·3 million in 2006.3 Despite this success, progress has been uneven and coverage for children has lagged behind.4
Antiretroviral therapy programmes face many obstacles in sub-Saharan Africa. These include a lack of trained physicians and other health-care workers available to provide antiretroviral therapy, poorly developed drug procurement and distribution systems,5, 6 and unaffordable assays for monitoring response to therapy (particularly HIV-1 viral load) and medication side-effects. These obstacles can be even more challenging in the provision of care to HIV-infected children. The diagnosis of HIV infection in infancy requires a higher level of technology than is currently available in most resource-poor settings; paediatric drug formulations are not widely available; health-care personnel are scarce and often untrained in the treatment, adherence monitoring, or counselling of HIV-infected children; and many health-care facilities have not developed policies and protocols to care for HIV-infected children.7, 8
Reports on the initial experiences of treatment programmes for HIV-infected children are beginning to emerge from sub-Saharan Africa and their evaluation is crucial to overcoming obstacles and improving the care of HIV-infected children. We review the effectiveness of paediatric antiretroviral therapy programmes in sub-Saharan Africa, specifically treatment outcomes, adherence, and mortality, and discuss the implications of these findings to improve the care of HIV-infected children in this region.
Section snippets
Methods
We searched the online databases PubMed and Web of Science for articles published in English before Oct 1, 2007, with the following terms: “HIV” AND “Africa” AND “antiretroviral” AND (“treatment” or “therapy”) AND (“pediatric” or “child”). Subject headings (PubMed only), titles, and abstracts were searched. The search identified 258 potential articles from PubMed and 133 from Web of Science. Titles and abstracts were reviewed to identify eligible articles. Articles were eligible (1) if they
Characteristics of programmes and children
Information on treatment initiation and immunological or virological outcomes were available from 30 studies (table 1). 27 of 29 (one study did not provide this information49) studies reported a period of enrolment after 2000, and over half of the studies (65%) reported results on fewer than 200 children, with the largest consisting of multisite studies,17, 44, 45 or studies from large urban areas with 200–4062 children (table 1).15, 18, 30, 43, 47, 50, 56, 59, 60 All studies were done in urban
Antiretroviral therapy regimens
24 of 30 studies described the antiretroviral regimens used (table 1). The most common regimen (92% of studies) included two nucleoside reverse-transcriptase inhibitors plus one non-nucleoside reverse-transcriptase inhibitor, typically a combination of zidovudine or stavudine, lamivudine, and efavirenz or nevirapine. Five studies (21%) reported using adult fixed-dose combinations of stavudine, lamivudine, and nevirapine.17, 18, 19, 31, 49 Fixed-dose combinations were used in an additional six
Clinical outcomes
The nutritional and clinical status of children im-proved in the 17 studies that examined these factors.13, 15, 16, 18, 19, 23, 30, 31, 37, 48, 49, 50, 53, 55, 60, 65, 66 On average, children gained 1·8–3·6 kg in the first year of treatment.19, 53, 55, 60, 66 In general, the mean or median weight-for-age Z scores were −2 or below at baseline and improved substantially by approximately 1 SD by 12 months of treatment.16, 18, 19, 23, 30, 31, 37, 49, 50 These improvements were maintained 2–3 years
Adherence
Adherence was assessed in 12 studies by various methods, including caregiver recall, pill counts at scheduled visits, and unannounced pill counts at home (table 2).11, 15, 20, 23, 25, 27, 31, 33, 50, 67, 69, 71, 72, 76 Compliance with scheduled visits was only reported in two studies and was 55%71 and 88%.69 However, the provision of more than 1 month's supply of drugs complicated this measure.71 Adherence by caregiver recall was reported to be 29–82% for perfect adherence in the specified time
Adverse events
The proportion of children experiencing adverse events associated with antiretroviral therapy varied from 2·5% in South Africa to 29% in Côte d'Ivoire, and is probably because of the different methods of classifying adverse events (table 3).13, 17, 18, 20, 26, 31, 48, 50, 54, 58, 68 Four of 11 studies reported that more than 20% of children had adverse events.13, 18, 31, 58 Most adverse events were mild, and the most common were gastrointestinal problems and skin rashes. Severe adverse events
Mortality and loss to follow-up
Mortality during follow-up was generally low (table 1): seven of nine studies with a duration of less than 1 year reported a mortality greater or equal to 5% (range 3–9%),15, 17, 19, 23, 24, 28, 31, 55, 66 four of 14 studies of 1–2 years had a mortality greater than 10% (range 0–15·4%),16, 18, 28, 29, 30, 45, 47, 48, 50, 51, 59, 62, 75, 78 and one of three studies of 3 years reported a mortality greater than 10% (range 5·0–11·5%).9, 56, 65 The probability of survival 1 year after the start of
Discussion
We identified 30 studies that described the treatment of HIV-infected children in sub-Saharan Africa and that provided information on clinical, immunological, or virological outcomes. The early treatment outcomes reported in these studies are similar to those seen in observational studies in North America and Europe, despite greater obstacles to care and treatment. As with children in sub-Saharan Africa, treatment responses among HIV-infected children in North America and Europe vary, with
Search strategy and selection criteria
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