Stanzi M. le Roux

Adherence to isoniazid prophylaxis among HIV-infected children: a randomized controlled trial comparing two dosing schedules

BackgroundTuberculosis contributes significantly to morbidity and mortality among HIV-infected children in sub-Saharan Africa. Isoniazid prophylaxis can reduce tuberculosis incidence in this population. However, for the treatment to be effective, adherence to the medication must be optimized. We investigated adherence to isoniazid prophylaxis administered daily, compared to three times a week, and predictors of adherence amongst HIV-infected children.MethodsWe investigated adherence to study medication in a two centre, randomized trial comparing daily to three times a week dosing of isoniazid. The study was conducted at two tertiary paediatric care centres in Cape Town, South Africa. Over a 5 year period, we followed 324 HIV-infected children aged ≥ 8 weeks. Adherence information based on pill counts was available for 276 children. Percentage adherence was calculated by counting the number of pills returned. Adherence ≥ 90% was considered to be optimal. Analysis was done using summary and repeated measures, comparing adherence to the two dosing schedules. Mean percentage adherence (per child during follow-up time) was used to compare the mean of each group as well as the proportion of children achieving an adherence of ≥ 90% in each group. For repeated measures, percentage adherence (per child per visit) was dichotomized at 90%. A logistic regression model with generalized estimating equations, to account for within-individual correlation, was used to evaluate the impact of the dosing schedule. Adjustments were made for potential confounders and we assessed potential baseline and time-varying adherence determinants.ResultsThe overall adherence to isoniazid was excellent, with a mean adherence of 94.7% (95% confidence interval [CI] 93.5-95.9); similar mean adherence was achieved by the group taking daily medication (93.8%; 95% CI 92.1-95.6) and by the three times a week group (95.5%; 95% CI 93.8-97.2). Two-hundred and seventeen (78.6%) children achieved a mean adherence of ≥ 90%. Adherence was similar for daily and three times a week dosing schedules in univariate (odds ratio [OR] 0.88; 95% CI 0.66-1.17; P = 0.38) and multivariate (adjusted OR 0.85; 95% CI 0.64-1.11; P = 0.23) models. Children from overcrowded homes were less adherent (adjusted OR 0.71; 95% CI 0.54-0.95; P = 0.02). Age at study visit was predictive of adherence, with better adherence achieved in children older than 4 years (adjusted OR 1.96; 95% CI 1.16-3.32; P = 0.01).ConclusionAdherence to isoniazid was excellent regardless of the dosing schedule used. Intermittent dosing of isoniazid prophylaxis can be considered as an alternative to daily dosing, without compromising adherence or efficacy.Trial registrationClinical Trials NCT00330304

South African measles outbreak 2009 - 2010 as experienced by a paediatric hospital

INTRODUCTION Between 2009 and 2010, South Africa experienced a major measles outbreak, with more than 18 000 confirmed cases reported to the National Institute of Communicable Diseases. METHODS We studied measles admissions during the outbreak to Red Cross War Memorial Childrens Hospital, Cape Town, between 1 November 2009 and 31 July 2010. Factors associated with mortality were retrospectively identified from notification records and hospital admissions data. Multivariate logistic regression was used to investigate potential risk factors for death. RESULTS In total, 1 861 children were diagnosed with measles; 552 (30%) were admitted to hospital. The most common reason for admission was pneumonia (379 (68%)) and/or diarrhoea (262 (48%)). The median age at admission was 7.36 months (interquartile range (IQR) 5.0 - 10.7). The median duration of admission was 4 days (IQR 2 - 6); total hospital admission time was 3 746 days (10.3 child-years). HIV status was known in 404 (73%) children: 39/400 (14%) were HIV-infected. Eighteen children died (3% of all admissions); 15 (83%) of them were less than 1 year old. In the regression model, HIV-infection (adjusted odds ratio (aOR) 7.55, 95% confidence interval (CI) 2.27 - 25.12) and female sex (aOR 3.86, 95% CI 1.26 - 11.84) were associated with higher odds of death. CONCLUSIONS There was a large paediatric admission burden during the 2009 - 2010 measles outbreak in Cape Town; young children were predominantly affected. HIV-infected children had a significantly higher case fatality.

Clinical outcomes of HIV-exposed, HIV-uninfected children in sub-Saharan Africa.

HIV‐exposed but HIV‐uninfected (HEU) children are widely considered at increased risk of mortality and morbidity. Recent advances in prevention of mother‐to‐child HIV transmission (PMTCT) strategies, incorporating life‐long universal maternal antiretroviral therapy (ART, “Option B+”) with extended breastfeeding, may improve HEU child health substantially. We critically reviewed reports of mortality/morbidity among HEU and HIV‐unexposed (HU) children in sub‐Saharan Africa.

A randomized controlled trial of intermittent compared with daily cotrimoxazole preventive therapy in HIV-infected children.

Objective:Cotrimoxazole preventive therapy (CPT) reduces morbidity and mortality in HIV-infected children. The WHO recommends prolonged daily CPT for HIV-infected infants and children. In adults, intermittent CPT has been associated with less adverse events than daily, with increased tolerability and equal efficacy. We investigated the efficacy and tolerability of intermittent CPT compared with daily CPT in HIV-infected children over a 5-year period. Design:A prospective randomized controlled study. Methods:HIV-infected children aged at least 8 weeks were randomized to thrice weekly or daily CPT. Outcome measures were mortality, bacterial infections, hospitalizations and adverse events. Results:Three hundred and twenty-four children (median age 23 months) were followed for 672 child-years; 165 (51%) were randomized to intermittent CPT. Most children (287, 89%) were Centers for Disease Control and Prevention clinical category B or C; 207 (64%) received HAART during the study. Mortality (53 deaths, 16%) was similar in the intermittent CPT compared with the daily CPT group {24 (14%) vs. 29 (18%), hazard ratio 0.75 [95% confidence interval (CI) 0.44–1.29]}. The predominant causes of death in both groups were sepsis (17, 32%), pneumonia (13, 25%) or diarrhoea (8, 15%). Intermittent CPT was associated with more bacteraemias [incidence rate ratio 2.36 (95% CI 1.21–4.86)]. Children receiving intermittent CPT also spent more days in hospital [incidence rate ratio 1.15 (95% CI 1.04–1.28)]. The rate of serious adverse events was similar between groups [incidence rate ratio 1.07 (95% CI 0.58–2.02)]. Conclusion:Intermittent CPT was associated with more invasive bacterial disease than daily CPT, but survival was similar. Both regimens were well tolerated. On balance, daily CPT remains preferable to intermittent therapy for HIV-infected children.

Bacteremia in human immunodeficiency virus-infected children in Cape Town, South Africa

Bacteremia contributes to morbidity of HIV-infected children. In a randomized controlled trial evaluating trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, 47 bacteremias were detected. The incidence rate of bacteremia increased in the first 3 months after starting combination antiretroviral therapy (cART), but decreased by 74% once children were established on cART for more than 3 months. Children should be prioritized for early cART.

Antiretroviral therapy use during pregnancy and adverse birth outcomes in South African women

Background Studies of antiretroviral therapy (ART) use during pregnancy in HIV-infected women have suggested that ART exposure may be associated with adverse birth outcomes. However, there are few data from sub-Saharan Africa where HIV is most common, and few studies involving the World Health Organizations (WHOs) recommended first-line regimens. Methods We enrolled consecutive HIV-infected pregnant women and a comparator cohort of uninfected women at a primary-level antenatal care facility in Cape Town, South Africa. Gestational assessment combined clinical history, examination and ultrasonography; outcomes included preterm (PTD), low birthweight (LBW) and small for gestational age (SGA) deliveries. In analysis we compared birth outcomes between HIV-infected and -uninfected women, and HIV-infected women who initiated ART before vs during pregnancy. Results In 1554 women (mean age 29 years) with live singleton births at time of analysis, 82% were HIV-infected, 92% of whom received a first-line regimen of tenofovir, emtricitabine and efavirenz. Overall, higher levels of PTD [22% vs 13%; odds ratio (OR) 1.94, 95% confidence interval (CI): 1.34, 2.82] and LBW (14% vs 9%; OR 1.62, 95% CI: 1.05, 2.29) were observed in HIV-infected vs uninfected women, although SGA deliveries were similar (9% vs 11%; OR 1.06, 95% CI: 0.71, 1.61). Adjusting for demographic characteristics and HIV disease measures, HIV-infected (vs HIV-uninfected) women had persistently increased odds of PTD [adjusted odds ratio (AOR) 2.03; CI 1.33, 3.10]; associations with LBW were attenuated (AOR 1.47; CI 0.90, 2.40). Among all HIV-infected women, there appeared to be no association between the timing of ART initiation (before or during pregnancy) and adverse birth outcomes. Conclusions These findings suggest that current WHO-recommended ART regimens appear relatively safe in pregnancy, although more data are required to understand the aetiology of preterm delivery in HIV-infected women using ART.

Rethinking the HIV-exposed, uninfected child: epidemiologic perspectives

Division of Epidemiology & Biostatistics, School of Public Health & Family Medicine, University of Cape Town, Anzio Road, Observatory 7925 Cape Town, South Africa Centre for Infectious Diseases Epidemiology & Research, School of Public Health & Family Medicine, University of Cape Town, South Africa ICAP, Columbia University Mailman School of Public Health, 10032 NY, USA *Author for correspondence: stanzi.leroux@uct.ac.za

Prevalence and determinants of unplanned pregnancy in HIV-positive and HIV-negative pregnant women in Cape Town, South Africa: a cross-sectional study

Objectives Prevention of unplanned pregnancy is a crucial aspect of preventing mother-to-child HIV transmission. There are few data investigating how HIV status and use of antiretroviral therapy (ART) may influence pregnancy planning in high HIV burden settings. Our objective was to examine the prevalence and determinants of unplanned pregnancy among HIV-positive and HIV-negative women in Cape Town, South Africa. Design Cross-sectional analysis. Settings Single primary-level antenatal care clinic in Cape Town, South Africa. Participants HIV-positive and HIV-negative pregnant women, booking for antenatal care from March 2013 to August 2015, were included. Main outcome measures Unplanned pregnancy was measured at the first antenatal care visit using the London Measure of Unplanned Pregnancy (LMUP). Analyses examined LMUP scores across four groups of participants defined by their HIV status, awareness of their HIV status prior to the current pregnancy and/or whether they were using antiretroviral therapy (ART) prior to the current pregnancy. Results Among 2105 pregnant women (1512 HIV positive; 593 HIV negative), median age was 28 years, 43% were married/cohabiting and 20% were nulliparous. Levels of unplanned pregnancy were significantly higher in HIV-positive versus HIV-negative women (50% vs 33%, p<0.001); and highest in women who were known HIV positive but not on ART (53%). After adjusting for age, parity and marital status, unplanned pregnancy was most common among women newly diagnosed and women who were known HIV positive but not on ART (compared with HIV-negative women, adjusted OR (aOR): 1.43; 95% CI 1.05 to 1.94 and aOR: 1.57; 95% CI 1.13 to 2.15, respectively). Increased parity and younger age (<24 years) were also associated with unplanned pregnancy (aOR: 1.42; 95% CI 1.25 to 1.60 and aOR: 1.83; 95% CI 1.23 to 2.74, respectively). Conclusions We observed high levels of unplanned pregnancy among HIV-positive women, particularly among those not on ART, suggesting ongoing missed opportunities for improved family planning and counselling services for HIV-positive women.