Search

Introduction: Little is known about virologic responses to early antiretroviral therapy (ART) in HIV-infected infants in resource-limited settings. We estimated the probability of achieving viral suppression within 2 years of ART initiation and investigated the factors associated with success., Methods: We analyzed all 190 infants from the Cameroon Pediacam who initiated ART by 12 months of age. The main outcome measure was viral suppression (<1000 copies/mL) on at least 1 occasion; the other outcome measures considered were viral suppression (<400 copies/mL) on at least 1 occasion and confirmed viral suppression (both thresholds) on 2 consecutive occasions. We used competing-risks regression for a time-to-event analysis to estimate the cumulative incidence of outcomes and univariate and multivariate models to identify risk factors., Results: During the first 24 months of ART, 20.0% (38) of the infants died, giving a mortality rate of 11.9 deaths per 100 infant-years (95% confidence interval: 8.1-15.7). The probability of achieving a viral load below 1000 or 400 copies/mL was 80.0% (69.0-81.0) and 78.0% (66.0-79.0), respectively. The probability of virologic suppression (with these 2 thresholds) on 2 consecutive occasions was 67.0% (56.0-70.0) and 60.0% (49.0-64.0), respectively. Virologic success was associated with not having missed any doses of treatment before the visit, but not with socioeconomic and living conditions., Conclusion: Many early treated children failed to achieve virologic suppression, likely due to a combination of adherence difficulties, drug dosing and viral resistance, which highlights the need for routine viral load monitoring. The high infant mortality despite early ART initiation needs to be addressed in sub-Saharan countries.

Objectives: To describe prevalence and risk factors for wasting and stunting among HIV-infected children with a median duration of 3 years of antiretroviral therapy (ART) at the time of their enrollment in the cohort study., Methods: Wasting and stunting at ART initiation and enrollment were defined as weight-for-height/body mass index-for-age Z scores < -2 and height-for-age Z scores < -2, respectively. Logistic regression was used to assess risk factors for wasting and stunting. Main predictive factors were age at enrollment, nutritional status and age (< or ≥5 years) at ART initiation and ART duration (< or ≥3 years on first-line, or ≥3 years including a switch to second-line ART)., Results: Two hundred forty-four children 2-16 years of age were enrolled. Overall, wasting and stunting prevalence dropped off consistently in children 2-10 years of age, between ART initiation and enrollment, while it remained at high levels, 52% and 42%, respectively, in children 10-16 years of age. Risk factors for wasting at enrollment were ART duration of ≥3 years including a switch to second-line [adjusted odds ratio (aOR): 3.9, 95% confidence interval (CI): 1.7-8.9] and wasting at ART initiation (aOR: 2.7, 95% CI: 1.4-5.2). The risk factor for stunting at enrollment was stunting at ART initiation (aOR: 11.6, 95% CI: 5.4-25.0), independent of ART duration., Conclusions: Malnutrition at the time of ART initiation was the main predictor of malnutrition at enrollment among HIV-infected children on ART. Longer duration on ART had no overall protective effect on wasting and stunting. Growth and virologic monitoring are of utmost importance in the comprehensive care of children with HIV infection.

Background: Although 90% of HIV-1-infected children live in sub-Saharan Africa, morbidity data after highly active antiretroviral therapy (HAART) initiation in these settings are limited. The objective of this study was to document the incidence of AIDS-defining events and non-AIDS-defining diseases in African children receiving HAART., Methods: Incidences rates (IRs) of AIDS-defining events and 10 other common diseases were estimated overall and by current CD4-strata (<15%, 15 - <25% and ≥25%) from 2 prospective cohorts of African children., Results: One hundred eighty-eight children contributing to 355 children-years were included. The documented morbidity IRs per 100 children-years were upper respiratory infections, 100 (87-114); infectious diarrhea, 37 (31-44); World Health Organization (WHO) stage 2 events, 22.9 (18.2-28.1); and WHO stage 3/4 events, 12.3 (9.1-16.7). IRs of WHO stage 2 events, severe bacterial infections, infectious diarrhea and pneumonia decreased linearly across all CD4%-strata, whereas WHO stage 3/4 events and viral infections occurred mostly when CD4% <15%. Overall, IRs decreased during the first 2 years on HAART except for upper respiratory infection, mycosis and oral candidiasis., Conclusion: This incidence of AIDS- and non-AIDS-defining diseases declined substantially after HAART in 2 African cohorts, although estimates remained high compared with high-resource settings. Without renewed efforts to increase antiretroviral scale-up, children in developing countries will continue to have a high burden of infections.

Objective: To estimate the frequency of human immunodeficiency virus type 1 (HIV-1) displaying genotypic drug resistance in highly active antiretroviral therapy (HAART)-treated children in Abidjan., Methods: Among the 269 HIV-1-infected children enrolled in the ANRS 1278 prospective observational cohort between October 2000 and September 2003, 115 [median age, 6.35 years (range, 1.2-15)] required treatment and received HAART for at least 6 months. Treatment consisted of 2 nucleoside analogue reverse transcriptase inhibitors associated with nelfinavir (70.5%) or efavirenz (29.5%). Plasma HIV-1 RNA and CD4+ T cell counts were determined at baseline and every 6 months thereafter. Genotypic resistance tests were performed in cases of virologic failure (viral load >or=3 log10 copies/mL) after at least 6 months of HAART., Results: After a median of 10.2 months of HAART, 66% (76 of 115) of children were in virologic success. Most of these children were infected with CRF02 strains. Twenty-seven viruses displayed resistance to at least 1 antiretroviral drug (27 of 38, 71%). Thirteen, 9 and 5 children had viruses with resistance to 1, 2 or 3 of the drugs included in their regimen, respectively. Resistance to lamivudine and/or to non-nucleoside analogue reverse transcriptase inhibitors was frequent among the 38 children in virologic failure. The 90M, 46L, 88S or 54V mutations were found in 11 (38%) of the 29 children taking nelfinavir. The overall frequency of viruses showing genotypic resistance to at least 1 antiretroviral drug was 23% (27 of 115) among the treated children., Conclusion: These results are similar to what is generally observed in industrialized countries. Despite these encouraging results, efforts are needed to maximize the long-term efficiency of treatment and to minimize the risk of emergence of drug resistance in treated children.

Introduction: Most data on tuberculosis in human immunodeficiency virus (HIV)-infected children in Africa come from hospital-based and cross-sectional studies., Objectives: To estimate the incidence of tuberculosis in HIV-infected children participating in an observational cohort., Methods: HIV-infected children in Abidjan, Côte d'Ivoire, are followed in a prospective cohort. At enrollment, all children had a physical examination, CD4 lymphocyte counts, chest radiograph and a tuberculin test. Quarterly follow-up visits are organized. All patients with suspected tuberculosis undergo specific investigations including gastric aspiration and culture. All isolates are tested for susceptibility., Results: From October 2000 to December 2003, 129 girls and 153 boys were recruited. Of children without a current or previous diagnosis of tuberculosis, 6.5% (13 of 199) had a tuberculin test result of >5 mm, compared with 17.5% of children (10 of 57) with current or previous tuberculosis (P < 0.02). Forty-eight children (17%) had a history of treated tuberculosis, and 27 children were being treated for tuberculosis at enrollment or during the first month of follow-up. Eleven children were diagnosed with tuberculosis after the first month of follow-up, and the diagnosis of mycobacterial infection was confirmed in 7 cases. Of 5 tested isolates of Mycobacterium tuberculosis, 3 were resistant to at least 1 antitubercular drug. Cumulative incidence of tuberculosis was 2060/100,000 at 12 months, 3390/100,000 at 2 years and 5930/100,000 at 3 years. The 3-year risk was 12,400/100,000 in immunocompromised children (CD4 <15%) and 3300/100,000 in other children (P < 0.0001)., Conclusion: The risk of tuberculosis among HIV-infected children in Côte d'Ivoire is strongly associated with the degree of immunodeficiency in HIV infection.

Objective: To compare the anthropometric characteristics of children with and without HIV-1 infection., Methods: In a prospective cohort study of 218 children born to HIV-1 seropositive mothers and 218 children born to HIV-1 seronegative mothers in Kigali, Rwanda, 3 groups were compared: infected children (n = 46); uninfected children born to seropositive mothers (n = 140); and uninfected children born to seronegative mothers (n = 207). Weight, height and head circumference were measured at birth, every 3 months during the first year of life and every 6 months thereafter. The weight-for-age, height-for-age, weight-for-height and head circumference-for-age mean z scores were calculated., Results: The weight-for-age, height-for-age and head circumference-for-age mean z scores were lower among HIV-infected children than among uninfected ones at each time period. The reduction in the weight-for-age mean z score was the greatest between 12 and 36 months. The reduction in the height-for-age mean z score of HIV-infected children was persistently below 2 SD after 9 months of age. On the other hand the weight-for-height mean z score was not consistently lower in HIV-infected children when compared with uninfected ones. The anthropometric characteristics of uninfected children born to seropositive mothers were similar to those of children born to seronegative mothers., Conclusions: In this study HIV-infected children were more frequently stunted (low height-for-age) than uninfected ones. Wasting (low weight-for-height) was not common among HIV-infected children.