Low prevalence of lipodystrophy in HIV-infected Senegalese children on long-term antiretroviral treatment: the ANRS 12279 MAGGSEN Pediatric Cohort Study.

BACKGROUND: The long-term benefits of antiretroviral treatment (ART) are associated with metabolic complications, especially lipodystrophy, which has been well described among HIV-infected adults and children on ART in developed settings. Specifically, stavudine, and to a lesser extent zidovudine and protease inhibitors (PI), have been consistently implicated in the development of lipodystrophy. In 2006, following advice from the WHO, Senegal began phasing out stavudine from first-line ART. The objectives of this cross-sectional analysis are to assess and identify risk factors affecting the prevalence of lipodystrophy in Senegalese children and adolescents on long-term ART participating in a cohort study. METHODS: Lipodystrophy was clinically assessed in two- to 18-year-old children on ART for at least six months and with no concurrent severe acute malnutrition. Risk factors for lipodystrophy were identified using stepwise multivariable logistic regression. Explanatory variables included clinical and personal data, immunovirologic status, and therapeutic history. RESULTS: Overall, 254 children were assessed for lipodystrophy. The median age was 10.9 years (IQR: 8.1-14.2) and the median duration on ART was 54 months (32-84). Only 18% had been previously treated with stavudine, with a median treatment duration of 8 months (5-25). Ongoing treatment included 76% of children receiving zidovudine (median duration of 48 months (26-74)) and 27% receiving PI (lopinavir/ritonavir; median duration of 49 months (23-59)). Mild signs of lipodystrophy were observed in 33 children (13%): 28 with lipoatrophy, 4 with lipohypertrophy and one with combined type. Boys were more likely to present with lipoatrophy than girls (aOR: 4.3, 95% CI: 1.6-11.7). Children previously treated with stavudine for ≥1 year had a greater risk for lipoatrophy than those never exposed (3.8, 1.0-14.0), although the association was weak. There was no association between lipodystrophy and age or current or cumulative treatment with lopinavir/ritonavir or zidovudine. CONCLUSIONS: We report low prevalence of mild lipodystrophy in children and adolescents on long-term ART receiving a stavudine-sparing regimen. These findings are reassuring for clinicians in low-income settings where zidovudine is massively prescribed and lopinavir/ritonavir is the only widely available PI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01771562 (registration date: 01/18/2013).

Risk Factors for Growth Retardation in HIV-infected Senegalese Children on Antiretroviral Treatment: The ANRS 12279 MAGGSEN Pediatric Cohort Study.

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.

Acceptability of Outpatient Ready-To-Use Food-Based Protocols in HIV-Infected Senegalese Children and Adolescents Within the MAGGSEN Cohort Study.

OBJECTIVES: To assess the acceptability of ready-to-use food (RUF)-based outpatient protocols in HIV-infected children and adolescents with severe acute malnutrition (SAM) and moderate acute malnutrition (MAM). METHODS: Plumpy Nut and Plumpy Sup were supplied every 2 weeks and prescribed by weight to SAM and MAM children, respectively. Forty-three children, 24 MAM and 19 SAM, were enrolled. Organoleptic appreciation, feeding modalities, and perceptions surrounding RUF were recorded at week 2. Sachets were counted to measure adherence throughout the study. RESULTS: Median age was 12.2 years (interquartile range: 9.3-14.8), and 91% were on antiretroviral treatment. Overall, 80%, 76%, 68%, and 68% of children initially rated RUF color, taste, smell, and mouth feeling as good. However, feelings of disgust, refusal to eat, fragmentation of intake, self-stigma, and sharing within the household were commonly reported. Eighteen MAM and 7 SAM experienced weight recovery. Recovery duration was 54 days (31-90) in MAM versus 114 days (69-151) in SAM children ( P = .02). Their rate of RUF consumption compared to amount prescribed was approximately 50% from week 2 to week 10. Nine failed to gain weight or consume RUF and were discontinued for clinical management, and 9 dropped out due to distance to the clinic. CONCLUSION: Initial RUF acceptability was satisfactory. More than half the children had successful weight recovery, although adherence to RUF prescription was suboptimal. However, further research is needed to propose therapeutic foods with improved palatability, alternative and simpler intervention design, and procedures for continuous and tailored psychosocial support in this vulnerable population. TRIAL REGISTRATION: NCT01771562 (Current Controlled Trials).

The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa.

The prevalence of human immunodeficiency virus (HIV) drug resistance mutations (DRMs) was estimated in 25 untreated infants who were living with HIV-1, younger than 13 months and living in Senegal. Antiretroviral DRMs were detected in 8 of 25 (32%) children. Non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs were present in all (100%) children whose viruses harboured DRMs: K103N in 43%; Y181C, K101E and V106M each in 29%; and Y188L in 14%. The D67N thymidine-analogue mutation was observed in only two children whose mothers had received chemoprophylaxis of mother-to-child transmission (MTCT). The proportion of children whose viruses harboured DRMs was then 6.5-fold higher in children whose mother-child couples had received nevirapine (NVP)-based chemoprophylaxis than in other couples without prophylaxis [7 of 13 (53.8%) vs. 1 of 12 (8.3%)]. These findings point to the absolute need to address primary resistance mutations in case of virological failure in young children treated by antiretroviral drugs, and to make more effective treatment regimens available to NVP-exposed infants living with HIV-1 in Senegal.