The long-term effectiveness of generic adult fixed-dose combination antiretroviral therapy for HIV-infected Ugandan children

Abstract

Background: Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs. Objective: To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment. Methods: Clinical, immunologic, and virologic outcomes of HIV-infected ART-naïve children aged six months to 12 years, were evaluated up to 96 weeks post-ART initiation. Results: From March 2004 to June 2006, 104 children were followed with a median age of 5.4 years, median CD4 cell percent and HIV-1 RNA were 11.0% (IQR 6.7-13.9) and 348,846copies/mL (IQR 160,941-681,313) respectively at baseline. Using Kaplan-Meir estimates, 75% of children had undetectable viral loads (<400copies/mL) at 96weeks of ART. Children with a baseline CD4 cell percent >15% were 3 times more likely to achieve viral load <400copies/mL than those with baseline CD4 cell percent <5% after adjusting for baseline age {aHR = 3.03 (1.10-8.32), p=0.03}; no difference was found among those with CD4 cell percent >5-14.9% and <5%. Conclusion: Treatment with generic adult FDC for HIV-infected Ugandan children led to sustained clinical, immunologic and virologic response during 96 weeks of ART. Early initiation of ART is key to achieving virological success.

Growth reconstitution following antiretroviral therapy and nutritional supplementation

“…Types of supplementation included: rice/corn and vegetable oil (Haiti [29]), high-energy protein (Zambia [24]), Plumpy’nut (Malawi [23]), other ready-to-use therapeutic food (Malawi [30]), nutritional porridge (Kenya [18, 31]), corn-soy blend ready-to-eat meal supplement (South Africa [32]), fortified amylase-enriched maize product (South Africa [28]), food supplementation or support (Malawi/Mozambique/Guinea [10], Ethiopia [8], Cambodia [33]), and multivitamins (Kenya [18], South Africa [32], Uganda [34], Uganda/Zimbabwe [35], and India [36]). One (Kenya [18]) study evaluated receipt and duration of nutritional supplementation in growth analyses, while a second (Malawi [30]) evaluated 6-month nutritional recovery in malnourished children initiating ART with ready-to-use therapeutic food.…”

“…A few studies provided information on nutritional supplements, all from RLS [5, 8, 10, 18, 23, 24, 29-32, 34, 37]. While many ART programs in RLS provide nutritional supplements during ART, most studies did not clearly specify eligibility criteria or duration of supplementation, and only two evaluated the impact of supplements on growth.…”

The Need for Pediatric Formulations to Treat Children with HIV

“…Many children have to take three or more pills or a combination of pills and liquids, every day, twice a day. The advent of fixed-dose combinations (FDCs), which combine two or three antiretroviral medications into one pill, has been shown to increase adherence in older children who are able to swallow pills [ 25 , 26 ]. Few FDCs exist in nonpill form, therefore limiting their administration to older children who are able to swallow large pills [ 27 ].…”

Immunologic and Virologic Responses to Nevirapine Based Antiretroviral Therapy (ART) Among HIV-tuberculosis Co-infected Ugandan Children on Rifampicin Based Anti-tubercular Treatment

“…Although a study done in Zambia and Malawi demonstrated that children who received half or quarter tablet of Triomune FDC were more likely to be under dosed with NVP as compared to those who received a full tablet findings from this observational cohort of Ugandan children showed sustained clinical, immunologic and virologic response in children who received the divided adult Triomune tablet. 11 Other studies in Sub Saharan Africa have demonstrated similar immunologic and virologic outcomes among children on Triomune FDC followed for 6-12 months as well as other newer NVP based pediatric FDCs. 26,27 The strengths of this study include the longitudinal laboratory and clinical monitoring as well as high rates of follow up in the parent study.…”

“…Exclusion criteria for the study included known hypersensitivity to Nevirepine (NVP), malignancy, or on current cytotoxic chemotherapy. 10,11 Before enrollment into the study, children underwent the standard screening procedures for the ART program as earlier described. Specifically for the study, these included adherence counseling, clinical and psychosocial assessments, details on history of single dose nevirapine (sdNVP) exposure and a home visit.…”