Secular trends in pediatric antiretroviral treatment programs in rural and urban Zambia: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Since 2003 pediatric antiretroviral treatment (ART) programs have scaled-up in sub-Saharan Africa and should be evaluated to assess progress and identify areas for improvement. We evaluated secular trends in the characteristics and treatment outcomes of children in three pediatric ART clinics in urban and rural areas in Zambia.</p> <p>Methods</p> <p>Routinely collected data were analyzed from three ART programs in rural (Macha and Mukinge) and urban (Lusaka) Zambia between program implementation and July 2008. Data were obtained from electronic medical record systems and medical record abstraction, and were categorized by year of program implementation. Characteristics of all HIV-infected and exposed children enrolled in the programs and all children initiating treatment were compared by year of implementation.</p> <p>Results</p> <p>Age decreased and immunologic characteristics improved in all groups over time in both urban and rural clinics, with greater improvement observed in the rural clinics. Among children both eligible and ineligible for ART at clinic enrollment, the majority started treatment within a year. A high proportion of children, particularly those ineligible for ART at clinic enrollment, were lost to follow-up prior to initiating ART. Among children initiating ART, clinical and immunologic outcomes after six months of treatment improved in both urban and rural clinics. In the urban clinics, mortality after six months of treatment declined with program duration, and in the rural clinics, the proportion of children defaulting by six months increased with program duration.</p> <p>Conclusions</p> <p>Treatment programs are showing signs of progress in the care of HIV-infected children, particularly in the rural clinics where scale-up increased rapidly over the first three years of program implementation. However, continued efforts to optimize care are needed as many children continue to enroll in ART programs at a late stage of disease and thus are not receiving the full benefits of treatment.</p

Severe morbidity and mortality in untreated HIV-infected children in a paediatric care programme in Abidjan, Côte d'Ivoire, 2004-2009

<p>Abstract</p> <p>Background</p> <p>Clinical evolution of HIV-infected children who have not yet initiated antiretroviral treatment (ART) is poorly understood in Africa. We describe severe morbidity and mortality of untreated HIV-infected children.</p> <p>Methods</p> <p>All HIV-infected children enrolled from 2004-2009 in a prospective HIV programme in two health facilities in Abidjan, Côte d'Ivoire, were eligible from their time of inclusion. Risks of severe morbidity (the first clinical event leading to death or hospitalisation) and mortality were documented retrospectively and estimated using cumulative incidence functions. Associations with baseline characteristics were assessed by competing risk regression models between outcomes and antiretroviral initiation.</p> <p>Results</p> <p>405 children were included at a median age of 4.5 years; at baseline, 66.9% were receiving cotrimoxazole prophylaxis, and 27.7% met the 2006 WHO criteria for immunodeficiency by age. The risk of developing a severe morbid event was 14% (95%CI: 10.7 - 17.8) at 18 months; this risk was lower in children previously exposed to any prevention of mother-to-child-transmission (PMTCT) intervention (adjusted subdistribution hazard ratio [sHR]: 0.16, 95% CI: 0.04 - 0.71) versus those without known exposure. Cumulative mortality reached 5.5% (95%CI: 3.5 - 8.1) at 18 months. Mortality was associated with immunodeficiency (sHR: 6.02, 95% CI: 1.28-28.42).</p> <p>Conclusions</p> <p>Having benefited from early access to care minimizes the severe morbidity risk for children who acquire HIV. Despite the receipt of cotrimoxazole prophylaxis, the risk of severe morbidity and mortality remains high in untreated HIV-infected children. Such evidence adds arguments to promote earlier access to ART in HIV-infected children in Africa and improve care interventions in a context where treatment is still not available to all.</p

Low Risk of Death, but Substantial Program Attrition, in Pediatric HIV Treatment Cohorts in Sub-Saharan Africa

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

Predictors of mortality among children on Antiretroviral Therapy at a referral hospital, Northwest Ethiopia: A retrospective follow up study

<p>Abstract</p> <p>Background</p> <p>An estimated 2.5 million children were living with HIV/AIDS at the end of 2009, 2.3 million (92%) in sub-Saharan Africa. Without treatment, a third of children with HIV will die of AIDS before their first birthday, half dying before two years of age. Hence, this study aimed to assess magnitude and predictors of mortality among children on Antiretroviral Therapy (ART) at a referral hospital in North-West Ethiopia.</p> <p>Methods</p> <p>Institution based retrospective follow up study was carried out among HIV-positive children from January 1^st, 2006 - March 31^st, 2011. Information on relevant variables was collected from patients’ charts and registries. Life table was used to estimate the cumulative survival of children. Log rank tests were employed to compare survival between the different categories of the explanatory variables. Multivariate Cox proportional hazards model was fitted to identify predictors of mortality.</p> <p>Results</p> <p>A total of 549 records were included in the analysis. The mean age at initiation of treatment was 6.35 ±3.78 SD years. The median follow up period was 22 months. At the end of the follow up, 41(7.5%) were dead and 384(69.9%) were alive. Mortality was 4.0 deaths per 100 child-years of follow-up period. The cumulative probabilities of survival at 3, 6, 12, 24, and 60 months of ART were 0.96, 0.94, 0.93, 0.92 and 0.83 respectively. Majority (90.2%) of the deaths occurred within the first year of treatment. Absence of cotrimoxazole preventive therapy (adjusted hazard ratio [AHR] = 4.74, 95% CI: 2.17, 10.34), anaemia (haemoglobin level < 10gm/dl) (AHR=2.44, 95% CI: 1.26, 4.73), absolute CD4 cell count below the threshold for severe immunodeficiency (AHR=2.24, 95% CI: 1.07, 4.69) and delayed or regressing developmental milestones at baseline (AHR=6.31, 95% CI: 2.52, 15.83) were predictors of mortality.</p> <p>Conclusions</p> <p>There was a high rate of early mortality. Hence, starting ART very early reduces disease progression and early mortality; close follow up of all children of HIV-positive mothers is recommended to make the diagnosis and start treatment at an earlier time before they develop severe immunodeficiency.</p

Cost-effectiveness of early infant HIV diagnosis of HIV-exposed infants and immediate antiretroviral therapy in HIV-infected children under 24 months in Thailand.

BACKGROUND: HIV-infected infants have high risk of death in the first two years of life if untreated. WHO guidelines recommend early infant HIV diagnosis (EID) of all HIV-exposed infants and immediate antiretroviral therapy (ART) in HIV-infected children under 24-months. We assessed the cost-effectiveness of this strategy in HIV-exposed non-breastfed children in Thailand. METHODS: A decision analytic model of HIV diagnosis and disease progression compared: EID using DNA PCR with immediate ART (Early-Early); or EID with deferred ART based on immune/clinical criteria (Early-Late); vs. clinical/serology based diagnosis and deferred ART (Reference). The model was populated with survival and cost data from a Thai observational cohort and the literature. Incremental cost-effectiveness ratio per life-year gained (LYG) was compared against the Reference strategy. Costs and outcomes were discounted at 3%. RESULTS: Mean discounted life expectancy of HIV-infected children increased from 13.3 years in the Reference strategy to 14.3 in the Early-Late and 17.8 years in Early-Early strategies. The mean discounted lifetime cost was $17,335,$22,583 and $29,108, respectively. The cost-effectiveness ratio of Early-Late and Early-Early strategies was$5,149 and $2,615 per LYG, respectively as compared to the Reference strategy. The Early-Early strategy was most cost-effective at approximately half the domestic product per capita per LYG ($4,420 in Thailand 2011). The results were robust in deterministic and probabilistic sensitivity analyses including varying perinatal transmission rates. CONCLUSION: In Thailand, EID and immediate ART would lead to major survival benefits and is cost- effective. These findings strongly support the adoption of WHO recommendations as routine care

A retrospective study of Human Immunodeficiency Virus transmission, mortality and loss to follow-up among infants in the first 18 months of life in a prevention of mother-to-child transmission programme in an urban hospital in KwaZulu-Natal, South Africa

<p>Abstract</p> <p>Background</p> <p>Follow up of Human Immunodeficiency Virus (HIV)-exposed infants is an important component of Prevention of Mother-to-Child Transmission (PMTCT) programmes in order to ascertain infant outcomes post delivery. We determined HIV transmission, mortality and loss to follow-up (LTFU) of HIV-exposed infants attending a postnatal clinic in an urban hospital in Durban, South Africa.</p> <p>Methods</p> <p>We conducted a retrospective cohort study of infants born to women in the PMTCT programme at McCord Hospital, where mothers paid a fee for service. Data were abstracted from patient records for live-born infants delivered between 1 May 2008 and 31 May 2009. The infants’ LTFU status and age was based on the date of the last visit. HIV transmission was calculated as a proportion of infants followed and tested at six weeks. Mortality rates were analyzed using Kaplan-Meier (K-M), with censoring on 15 January 2010, LTFU or death.</p> <p>Results</p> <p>Of 260 infants, 155 (59.6%) remained in care at McCord beyond 28 weeks: one died at < 28 days, three died between one to six months; 34 were LTFU within seven days, 60 were LTFU by six months. K-M mortality rate: 1.7% at six months (95% confidence interval (CI): 0.6% to 4.3%). Of 220 (83%) infants tested for HIV at six weeks, six (2.7%, 95% CI: 1.1% to 5.8%) were HIV-infected. In Cox regression analysis, late antenatal attendance (≥ 28 weeks gestation) relative to attending in the first trimester was a predictor for infant LTFU (adjusted hazards ratio = 2.3; 95% CI: 1.0 to 5.1; p = 0.044).</p> <p>Conclusion</p> <p>This urban PMTCT programme achieved low transmission rates at six weeks, but LTFU in the first six months limited our ability to examine HIV transmission up to 18 months and determinants of mortality. The LTFU of infants born to women who attended antenatal care at 28 weeks gestation or later emphasizes the need to identify late antenatal attendees for follow up care to educate and support them regarding the importance of follow up care for themselves and their infants.</p