Growth response to antiretroviral treatment in HIV‐infected children: a cohort study from Lilongwe,Malawi

Objective Malnutrition is common in HIV‐infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public‐sector clinic in Malawi. Methods All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008. Weight and height were measured at regular intervals from 1 year before to 2 years after the start of ART. Sex‐ and age‐standardized z‐scores were calculated for weight‐for‐age (WAZ) and height‐for‐age (HAZ). Predictors of growth were identified in multivariable mixed‐effect models. Results A total of 497 children started ART and were followed for 972 person‐years. Median age (interquartile range; IQR) was 8 years (4–11 years). Most children were underweight (52% of children), stunted (69%), in advanced clinical stages (94% in WHO stages 3 or 4) and had severe immunodeficiency (77%). After starting ART, median (IQR) WAZ and HAZ increased from ?2.1 (?2.7 to ?1.3) and ?2.6 (?3.6 to ?1.8) to ?1.4 (?2.1 to ?0.8) and ?1.8 (?2.4 to ?1.1) at 24 months, respectively (P < 0.001). In multivariable models, baseline WAZ and HAZ scores were the most important determinants of growth trajectories on ART. Conclusions Despite a sustained growth response to ART among children remaining on therapy, normal values were not reached. Interventions leading to earlier HIV diagnosis and initiation of treatment could improve growth response.     

Low mortality risk but high loss to follow‐up among patients in the Tanzanian national HIV care and treatment programme

Objective To analyse survival and retention rates of the Tanzanian care and treatment programme. Methods Routine patient‐level data were available from 101 of 909 clinics. Kaplan–Meier probabilities of mortality and attrition after ART initiation were calculated. Mortality risks were corrected for biases from loss to follow‐up using Egger’s nomogram. Smoothed hazard rates showed mortality and attrition peaks. Cox regression identified factors associated with death and attrition. Median CD4 counts were calculated at 6 month intervals. Results In 88,875 adults, 18% were lost to follow up 12 months after treatment initiation, and 36% after 36 months. Cumulative mortality reached 10% by 12 months (15% after correcting for loss to follow‐up) and 14% by 36 months. Mortality and attrition rates both peaked within the first six months, and were higher among males, those under 45 kg and those with CD4 counts below 50 cells/μl at ART initiation. In the first year on ART, median CD4 count increased by 126 cells/μl, with similar changes in both sexes. Conclusion Earlier diagnoses through expanded HIV testing may reduce high mortality and attrition rates if combined with better patient tracing systems. Further research is needed to explore reasons for attrition.     

Access to maternal and perinatal health services: lessons from successful and less successful examples of improving access to safe delivery and care of the newborn

The huge majority of the annual 6.3 million perinatal deaths and half a million maternal deaths take place in developing countries and are avoidable. However, most of the interventions aiming at reducing perinatal and maternal deaths need a health care system offering appropriate antenatal care and quality delivery care, including basic and comprehensive emergency obstetric care facilities. To promote the uptake of quality care, there are two possible approaches: influencing the demand and/or the supply of care. Five lessons emerged from experiences. First, it is difficult to obtain robust evidence of the effects of a particular intervention in a context, where they are always associated with other interventions. Second, the interventions tend to have relatively modest short‐term impacts, when they address only part of the health system. Third, the long‐term effects of an intervention on the whole health system are uncertain. Fourth, because newborn health is intimately linked with maternal health, it is of paramount importance to organise the continuum of care between mother and newborn. Finally, the transfer of experiences is delicate, and an intervention package that has proved to have a positive effect in one setting may have very different effects in other settings.     

Retention of HIV‐infected and HIV‐exposed children in a comprehensive HIV clinical care programme in Western Kenya

Background 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. Methods 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 enrolment, 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 ≤?3.0. Immune suppression was defined as per WHO age‐specific categories. Results There were 13 510 children eligible for analysis, comprising 3106 children who at enrolment 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 enrolment (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). Conclusions 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.     

How to improve the validity of sexual behaviour reporting: systematic review of questionnaire delivery modes in developing countries

Objectives To systematically review comparative research from developing countries on the effects of questionnaire delivery mode. Methods We searched Medline, EMbase and PsychINFO and ISSTDR conference proceedings. Randomized control trials and quasi‐experimental studies were included if they compared two or more questionnaire delivery modes, were conducted in a developing country, reported on sexual behaviours and occurred after 1980. Results A total of 28 articles reporting on 26 studies met the inclusion criteria. Heterogeneity of reported trial outcomes between studies made it inappropriate to combine trial outcomes. Eighteen studies compared audio computer‐assisted survey instruments (ACASI) or its derivatives [personal digital assistant (PDA) or computer‐assisted personal interview (CAPI)] against another self‐administered questionnaires, face‐to‐face interviews or random response technique. Despite wide variation in geography and populations sampled, there was strong evidence that computer‐assisted interviews lowered item‐response rates and raised rates of reporting sensitive behaviours. ACASI also improved data entry quality. A wide range of sexual behaviours were reported including vaginal, oral, anal and/or forced sex, age of sexual debut, condom use at first and/or last sex. Validation of self‐reports using biomarkers was rare. Conclusions These data reaffirm that questionnaire delivery modes do affect self‐reported sexual behaviours and that use of ACASI can significantly reduce reporting bias. Its acceptability and feasibility in developing country settings should encourage researchers to consider its use when conducting sexual health research. Triangulation of self‐reported data using biomarkers is recommended. Standardizing sexual behaviour measures would allow for meta‐analysis.     

Septicaemia in a population‐based HIV clinical cohort in rural Uganda, 1996–2007: incidence,aetiology, antimicrobial drug resistance and impact of antiretroviral therapy

Objectives To describe the incidence and aetiology of septicaemia, and antimicrobial drug resistance in HIV‐infected and uninfected individuals, and the impact of antiretroviral therapy (ART) on septicaemia. Methods Between 1996 and 2007, we followed up a rural population–based cohort of HIV‐infected and uninfected participants. The aetiology and incidence of septicaemia, and antimicrobial drug resistances were determined. ART became available in 2004, and its impact on the incidence of septicaemia was examined. Results The overall septicaemia incidence (per 1000 pyrs) was 32.4 (95% CI 26.2–40.6) but was only 2.6 (95% CI 1.3–6.2) in HIV‐negative patients and 67.1 (95% CI 53.4–85.4) in HIV‐positive patients not on ART. Among those on ART, the overall incidence was 71.5 (95% CI 47.1–114.3), although it was 121.4 (95%CI 77.9–200.4) in the first year on ART and 37.4 (95%CI 18.9–85.2) in the subsequent period. Septicaemia incidence was significantly associated with lower CD4 counts. The commonest isolates were Streptococcus pneumoniae (SPN, n = 68) and Non‐typhi salmonellae (NTS, n = 42). Most SPN isolates were susceptible to ceftriaxone and erythromycin, while resistance to cotrimoxazole and penicillin was common. All NTS isolates were susceptible to ciprofloxacin, but resistance to cotrimoxazole and chloramphenicol was common. Conclusions Septicaemia incidence was higher in HIV‐infected than in HIV‐uninfected participants, and it remained high for some time among those who started ART. Starting ART earlier at higher CD4 counts is likely to lead to lower septicaemia incidence. Both SPN and NTS, the commonest isolates, were resistant to most commonly available antimicrobials. Blood culture laboratory surveillance systems to monitor antibiotic susceptibility and inform treatment guidelines are needed in Africa.