Review
Effectiveness of antiretroviral therapy among HIV-infected children in sub-Saharan Africa

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Summary

Assessment of antiretroviral treatment programmes for HIV-infected children in sub-Saharan Africa is important to enable the development of effective care and improve treatment outcomes. We review the effectiveness of paediatric antiretroviral treatment programmes in sub-Saharan Africa and discuss the implications of these findings for the care and treatment of HIV-infected children in this region. Available reports indicate that programmes in sub-Saharan Africa achieve treatment outcomes similar to those in North America and Europe. However, progress in several areas is required to improve the care of HIV-infected children in sub-Saharan Africa. The findings emphasise the need for low-cost diagnostic tests that allow for earlier identification of HIV infection in infants living in sub-Saharan Africa, improved access to antiretroviral treatment programmes, including expansion of care into rural areas, and the integration of antiretroviral treatment programmes with other health-care services, such as nutritional support.

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

These are described in detail in the Methods section on page 477.

References (108)

  • W Stevens et al.

    Antiretroviral therapy in Africa

    BMJ

    (2004)
  • AJ De Baets et al.

    Care and treatment of HIV-infected children in Africa: issues and challenges at the district hospital level

    Pediatr Infect Dis J

    (2007)
  • D Fransman et al.

    Doctors' attitudes to the care of children with HIV in South Africa

    AIDS Care

    (2000)
  • F Rouet et al.

    Long-term survival and immuno-virological response of African HIV-1-infected children to highly active antiretroviral therapy regimens

    AIDS

    (2006)
  • ML Chaix et al.

    Genotypic human immunodeficiency virus type 1 drug resistance in highly active antiretroviral therapy-treated children in Abidjan, Côte d'Ivoire

    Pediatr Infect Dis J

    (2005)
  • A Elise et al.

    Assessment of adherence to highly active antiretroviral therapy in a cohort of African HIV-infected children in Abidjan, Côte d'Ivoire

    J Acquir Immune Defic Syndr

    (2005)
  • P Fassinou et al.

    Highly active antiretroviral therapies among HIV-1-infected children in Abidjan, Côte d'Ivoire

    AIDS

    (2004)
  • WM Nyandiko et al.

    Outcomes of HIV-infected orphaned and non-orphaned children on antiretroviral therapy in western Kenya

    J Acquir Immune Defic Syndr

    (2006)
  • C Ble et al.

    Efficacy of highly active antiretroviral therapy in HIV-infected, institutionalized orphaned children in Tanzania

    Acta Paediatr

    (2007)
  • DP O'Brien et al.

    In resource-limited settings good early outcomes can be achieved in children using adult fixed-dose combination antiretroviral therapy

    AIDS

    (2006)
  • MC Marazzi et al.

    Pediatric highly active antiretroviral therapy in Mozambique: an integrated model of care

    Minerva Pediatr

    (2006)
  • AS Walker et al.

    The impact of daily cotrimoxazole prophylaxis and antiretroviral therapy on mortality and hospital admissions in HIV-infected Zambian children

    Clin Infect Dis

    (2007)
  • B Eley et al.

    Initial experience of a public sector antiretroviral treatment programme for HIV-infected children and their infected parents

    S Afr Med J

    (2004)
  • M Zampoli et al.

    Tuberculosis during early antiretroviral-induced immune reconstitution in HIV-infected children

    Int J Tuberc Lung Dis

    (2007)
  • A Reddi et al.

    Preliminary outcomes of a paediatric highly active antiretroviral therapy cohort from KwaZulu-Natal, South Africa

    BMC Pediatr

    (2007)
  • JP Jooste et al.

    Antiretroviral treatment in the Northern Cape

    S Afr Med J

    (2005)
  • W Bikaako-Kajura et al.

    Disclosure of HIV status and adherence to daily drug regimens among HIV-infected children in Uganda

    AIDS Behav

    (2006)
  • MA Diack et al.

    Epidemiological and clinical aspects of paediatric HIV infections in Albert-Royer Paediatric Hospital (Dakar, Senegal)

    Arch Pediatr

    (2005)
  • N Nabukeera-Barungi et al.

    Adherence to antiretroviral therapy in children attending Mulago Hospital, Kampala

    Ann Trop Paediatr

    (2007)
  • Antiretroviral therapy for children in the routine setting in Malawi

    Trans R Soc Trop Med Hyg

    (2007)
  • CN Bong et al.

    Risk factors for early mortality in children on adult fixed-dose combination antiretroviral treatment in a central hospital in Malawi

    AIDS

    (2007)
  • B Eley et al.

    Antiretroviral treatment for children

    S Afr Med J

    (2006)
  • DC Wamalwa et al.

    Early response to highly active antiretroviral therapy in HIV-1-infected Kenyan children

    J Acquir Immune Defic Syndr

    (2007)
  • Nyandiko-Mokaya W, Ayaya S, Nabakwe E, et al. Outcomes of HIV-infected orphaned and non-orphaned children on...
  • Wiehe SE, Vreeman RC, Musick BS, et al. Orphan status and pediatric anti-retroviral therapy adherence in a...
  • Obimbo E, Wamalwa D, Inwani I, et al. Model of comprehensive care for HIV-infected children in Nairobi, Kenya....
  • Wamalwa D, Farquhar C, Obimbo E, et al. Adherence and early response to highly active antiretroviral therapy in Kenyan...
  • Olson D, Sauvageot D, Ferradini L, et al. Antiretroviral therapy (ART) outcomes in children <13 years of age in...
  • Humblet P, Calmy A, Pinoges L, et al. Offering HAART to children in resource-poor settings: the experience of Medecins...
  • Liotta G, Germano P, Palombi L, et al. Pediatric HAART in resource-limited settings: the DREAM model of care....
  • Nuttall J, Eley B, Davies MA, et al. Serious medical events in children during the first six months of HAART....
  • Eley B, Nuttall J, Davies MA, et al. Initial experience of a public sector antiretroviral treatment programme for...
  • Reddi A, Leeper S, Grobler A, et al. Outcomes of a paediatric highly active antiretroviral therapy cohort from...
  • Nkengasong J, Adje-Toure C, Hanson D, et al. Virologic and immunologic response to ART and predictors of HIV-1 drug...
  • Mahan L, Kouakoussui A, Toure S. Following-up a children HIV-infected cohort in the context of extending access to care...
  • Kline M, Anabwani G, Kekitiinwa A, et al. Catalyzing the care and treatment of HIV-infected children in sub-Saharan...
  • Carter R, Katyal M, Austin J, et al. Age and CD4 percentage at ART initiation: relationship to CD4 response over time...
  • Warren H, Bruce D, Armstrong D, et al. The effect of ARV treatment, counseling and adherence support on CD4 counts in...
  • Kamya MR, Mayanja-Kizza H, Kambugu A, et al. Predictors of long-term viral failure among Ugandan children and adults...
  • Nannyonga Musoke M, Morelli E, Atai B, et al. Efficacy of HAART in Ugandan HIV-infected children. Proceedings of the...
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