Suchergebnisse

IntroductionAs access to prevention of mother‐to‐child transmission (PMTCT) efforts has increased, the total number of children being born with HIV has significantly decreased. However, those children who do become infected after PMTCT failure are at particular risk of HIV drug resistance, selected by exposure to maternal or paediatric antiretroviral drugs used before, during or after birth. As a consequence, the response to antiretroviral therapy (ART) in these children may be compromised, particularly when non‐nucleoside reverse transcriptase inhibitors (NNRTIs) are used as part of the first‐line regimen. We review evidence guiding choices of first‐ and second‐line ART.DiscussionChildren generally respond relatively well to ART. Clinical trials show the superiority of protease inhibitor (PI)‐ over NNRTI‐based treatment in young children, but observational reports of NNRTI‐containing regimens are usually favourable as well. This is reassuring as national guidelines often still recommend the use of NNRTI‐based treatment for PMTCT‐unexposed young children, due to the higher costs of PIs. After failure of NNRTI‐based, first‐line treatment, the rate of acquired drug resistance is high, but HIV may well be suppressed by PIs in second‐line ART. By contrast, there are currently no adequate alternatives in resource‐limited settings (RLS) for children failing either first‐ or second‐line, PI‐containing regimens.ConclusionsAffordable salvage treatment options for children in RLS are urgently needed.

IntroductionPre‐treatment HIV drug resistance (PDR) is an increasing problem in sub‐Saharan Africa. Children are an especially vulnerable population to develop PDR given that paediatric second‐line treatment options are limited. Although monitoring of PDR is important, data on the paediatric prevalence in sub‐Saharan Africa and its consequences for treatment outcomes are scarce. We designed a prospective paediatric cohort study to document the prevalence of PDR and its effect on subsequent treatment failure in Nigeria, the country with the second highest number of HIV‐infected children in the world.MethodsHIV‐1‐infected children ≤12 years, who had not been exposed to drugs for the prevention of mother‐to‐child transmission (PMTCT), were enrolled between 2012 and 2013, and followed up for 24 months in Lagos, Nigeria. Pre‐antiretroviral treatment (ART) population‐based pol genotypic testing and six‐monthly viral load (VL) testing were performed. Logistic regression analysis was used to assess the effect of PDR (World Health Organization (WHO) list for transmitted drug resistance) on subsequent treatment failure (two consecutive VL measurements >1000 cps/ml or death).ResultsOf the total 82 PMTCT‐naïve children, 13 (15.9%) had PDR. All 13 children harboured non‐nucleoside reverse transcriptase inhibitor (NNRTI) mutations, of whom seven also had nucleoside reverse transcriptase inhibitor resistance. After 24 months, 33% had experienced treatment failure. Treatment failure was associated with PDR and a higher log VL before treatment initiation (adjusted odds ratio (aOR) 7.53 (95%CI 1.61–35.15) and 2.85 (95%CI 1.04–7.78), respectively).DiscussionPDR was present in one out of six Nigerian children. These high numbers corroborate with recent findings in other African countries. The presence of PDR was relevant as it was the strongest predictor of first‐line treatment failure.ConclusionsOur findings stress the importance of implementing fully active regimens in children living with HIV. This includes the implementation of protease inhibitor (PI)‐based first‐line ART, as is recommended by the WHO for all HIV‐infected children <3 years of age. Overcoming practical barriers to implement PI‐based regimens is essential to ensure optimal treatment for HIV‐infected children in sub‐Saharan Africa. In countries where individual VL or resistance testing is not possible, more attention should be given to paediatric PDR surveys.

AbstractIntroduction: The number of HIV‐infected children and adolescents requiring second‐line antiretroviral treatment (ART) is increasing in low‐ and middle‐income countries (LMIC). However, the effectiveness of paediatric second‐line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second‐line ART outcomes for children and assessed the need for paediatric third‐line ART.Methods: We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second‐line ART in LMIC, contacting the corresponding study groups and including patient‐level data on virologic and clinical outcomes. Kaplan–Meier survival estimates and Cox proportional hazard models were used to describe cumulative rates and predictors of virologic failure. Virologic failure was defined as two consecutive viral load measurements >1000 copies/ml after at least six months of second‐line treatment.Results: We included 12 cohorts representing 928 children on second‐line protease inhibitor (PI)‐based ART in 14 countries in Asia and sub‐Saharan Africa. After 24 months, 16.4% (95% confidence interval (CI): 13.9–19.4) of children experienced virologic failure. Adolescents (10–18 years) had failure rates of 14.5 (95% CI 11.9–17.6) per 100 person‐years compared to 4.5 (95% CI 3.4–5.8) for younger children (3–9 years). Risk factors for virologic failure were adolescence (adjusted hazard ratio [aHR] 3.93, p < 0.001) and short duration of first‐line ART before treatment switch (aHR 0.64 and 0.53, p = 0.008, for 24–48 months and >48 months, respectively, compared to <24 months).Conclusions: In LMIC, paediatric PI‐based second‐line ART was associated with relatively low virologic failure rates. However, adolescents showed exceptionally poor virologic outcomes in LMIC, and optimizing their HIV care requires urgent attention. In addition, 16% of children and adolescents failed PI‐based treatment and will require integrase inhibitors to construct salvage regimens. These drugs are currently not available in LMIC.