Low risk of death, but substantial program attrition in pediatric HIV treatment cohorts in Sub-Saharan AfricaKIDS-ART-LINC CollaborationJ Acquir Immune Defic Syndr20084952353118989227
Background: To date, an estimated 10% of children eligible for antiretroviral treatment (ART) receive it, and the frequency of retention in programs is unknown. We evaluated the 2-year risks of death and loss to follow-up (LTFU) of children after ART initiation in a multicenter study in sub-Saharan Africa. Methods: Pooled analysis of routine individual data from 16 participating clinics produced overall Kaplan-Meier estimates of the probabilities of death or LTFU after ART initiation. Risk factors analysis used Weibull regression, accounting for between-cohort heterogeneity. Results: The median age of 2405 children at ART initiation was 4.9 years (12%, younger than 12 months), 52% were male, 70% had severe immunodeficiency, and 59% started ART with a nonnucleoside reverse transcriptase inhibitor. The 2-year risk of death after ART initiation was 6.9% (95% confidence interval [CI]: 5.9 to 8.1), independently associated with baseline severe anemia (adjusted hazard ratio [aHR]: 4.10 [CI: 2.36 to 7.13]), immunodeficiency (adjusted aHR: 2.95 [CI: 1.49 to 5.82]), and severe clinical status (adjusted aHR: 3.64 [CI: 1.95 to 6.81]); the 2-year risk of LTFU was 10.3% (CI: 8.9 to 11.9), higher in children with severe clinical status. Conclusions: Once on treatment, the 2-year risk of death is low but the LTFU risk is substantial. ART is still mainly initiated at advanced disease stage in African children, reinforcing the need for early HIV diagnosis, early initiation of ART, and procedures to increase program retention.
Available from: Jeffrey S Stringer
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ABSTRACT: To describe the pattern of incident illness in children after initiation of antiretroviral therapy (ART) in a large public health sector programme in Lusaka, Zambia.
Systematic chart review to retrospectively extract data from medical records of children (i.e. <15 years) initiating ART in the Lusaka, Zambia public sector. Incident conditions were listed separately and then grouped according to broad categories. Predictors for incident diagnoses were determined using univariate and multivariable analysis.
Between May 2004 and June 2006, 1705 HIV-infected children initiated ART. Of these, 1235 (72%) had their medical records reviewed. Median age at ART initiation was 77 months and 554 (45%) were females. Eight hundred and forty-one (68%) children had an incident condition during this period, with a median time of occurrence of 64 days from ART initiation. Twenty-eight incident conditions were documented. When categorized, the most common were mucocutaneous conditions [incidence rate (IR): 70.6 per 100 child-years, 95% CI: 64.5-77.2] and upper respiratory tract infection (IR: 70.1 per 100 child-years; 95% CI: 64.0-76.7). Children with severe immunosuppression (i.e. CD4 < 10%) were more likely to develop lower respiratory tract infection (16.3%vs. 10.2%; P = 0.003) and mucocutaneous conditions (43.9% vs. 35.3%; P = 0.005) than those with CD4 > or = 10%.
There is a high incidence of new illness after ART initiation, emphasizing the importance of close monitoring during this period. Early initiation of ART and use of antimicrobial prophylaxis may also help to reduce the occurrence of such co-morbidities.
Tropical Medicine & International Health 09/2009; 14(10):1190-8. DOI:10.1111/j.1365-3156.2009.02360.x · 2.33 Impact Factor
Available from: Kara Wools-Kaloustian
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ABSTRACT: To describe incidence rates (IR) and risk factors for loss-to-follow-up (LTFU) among HIV-infected and HIV-exposed children in a large HIV treatment programme in Western Kenya.
The USAID-AMPATH Partnership has enrolled >100,000 patients (20% children) at 23 clinic sites throughout western Kenya. LTFU is defined as being absent from the clinic for >3 months if on combination antiretroviral treatment (cART) and >6 months if not. Included in this analysis were children aged <14 years, HIV exposed or infected at enrollment, and enrolled between April 2002 and March 2009. The IR for LTFU are presented per 100 child-years (CY) of follow-up. Proportional hazards models with time-independent and time-dependent covariates were used to model factors associated with LTFU. Weight for height Z-scores were calculated using EpiInfo, with severe malnutrition being defined as a Z-score <or=-3.0. Immune suppression was defined as per WHO age-specific categories.
There were 13,510 children eligible for analysis, comprising 3106 children who at enrollment were HIV infected and 10,404 children who were HIV exposed. The overall IR of LTFU was 18.4 (17.8-18.9) per 100 CY. Among HIV-infected children, 15.2 (13.8-16.7) and 14.1 (13.1-15.8) per 100 CY became LTFU, pre- and post-cART initiation, respectively. The only independent risk factor for becoming LTFU among the HIV-infected children was severe immune suppression (AHR: 2.17, 95% CI: 1.51-3.12). Among the HIV-exposed children, 20.1 per 100 (19.4-20.7) became LTFU. Independent risk factors for LTFU among them were being severely low weight for height (AHR: 1.69, 95% CI: 1.25-2.28), being orphaned at enrollment (AHR: 1.57, 95% CI: 1.23-1.64), being CDC Class B or C (AHR: 1.41, 95% CI: 1.14-1.74), and having received cART (AHR: 1.56, 95% CI: 1.23-1.99). Protective against becoming LTFU among the HIV exposed were testing HIV positive (AHR: 0.26, 95% CI: 0.21-0.32), older age (AHR: 0.90, 95% CI: 0.85-0.96), enrolling in later time periods, and receiving food supplementation (AHR: 0.58, 95% CI: 0.32-1.04).
There is a high rate of LTFU among these highly vulnerable children, particularly among the HIV exposed. These data suggest that HIV-infected and HIV-exposed children are at especially high risk for LTFU if they are sick or malnourished.
Tropical Medicine & International Health 07/2010; 15(7):833-41. DOI:10.1111/j.1365-3156.2010.02539.x · 2.33 Impact Factor
Available from: Suerie Moon
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ABSTRACT: Important advances in the development and production of quality-certified pediatric antiretroviral (ARV) formulations have recently been made despite significant market disincentives for manufacturers. This progress resulted from lobbying and innovative interventions from HIV/AIDS activists, civil society organizations, and international organizations. Research on uptake and dispersion of these improved products across countries and international organizations has not been conducted but is needed to inform next steps towards improving child health.
We used information from the World Health Organization Prequalification Programme and the United States Food and Drug Administration to describe trends in quality-certification of pediatric formulations and used 7,989 donor-funded, pediatric ARV purchase transactions from 2002-2009 to measure uptake and dispersion of new pediatric ARV formulations across countries and programs. Prices for new pediatric ARV formulations were compared to alternative dosage forms.
Fewer ARV options exist for HIV/AIDS treatment in children than adults. Before 2005, most pediatric ARVs were produced by innovator companies in single-component solid and liquid forms. Five 2-in1 and four 3-in-1 generic pediatric fixed-dose combinations (FDCs) in solid and dispersible forms have been quality-certified since 2005. Most (67%) of these were produced by one quality-certified manufacturer. Uptake of new pediatric FDCs outside of UNITAID is low. UNITAID accounted for 97-100% of 2008-2009 market volume. In total, 33 and 34 countries reported solid or dispersible FDC purchases in 2008 and 2009, respectively, but most purchases were made through UNITAID. Only three Global Fund country recipients reported purchase of these FDCs in 2008. Prices for pediatric FDCs were considerably lower than liquids but typically higher than half of an adult FDC.
Pediatric ARV markets are more fragile than adult markets. Ensuring a long-term supply of quality, well-adapted ARVs for children requires ongoing monitoring and improved understanding of global pediatric markets, including country-based research to explain and address low uptake of new, improved formulations. Continued innovation in pediatric ARV development may be threatened by outdated procurement practices failing to connect clinicians making prescribing decisions, supply chain staff dealing with logistics, donors, international organizations, and pharmaceutical manufacturers. Perceptions of global demand must be better informed by accurate estimates of actual country-level demand.
BMC Pediatrics 10/2010; 10(1):74. DOI:10.1186/1471-2431-10-74 · 1.93 Impact Factor
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