Genotype-guided antiretroviral regimens in children with multidrug-resistant HIV-1 infection

Abstract

Background: Genotyping tests were developed to attenuate the impact of viral resistance. Information about the efficacy in genotype base antiretroviral therapy in children is rare and even more in low-and middle-income countries. Methods: Sixteen children with antiretroviral therapy (ART) failure and triple-class drug-resistant viruses were included in this study. Protease and retrotranscriptase genotypes were available for all patients. Switch of ART regimen was guided by genotyping data. The primary end point was virological suppression (<50 copies/ml) and immunological improvement after 48 wk of treatment with the new ART regimen. results: The median age of the patients was 14.5 y (interquartile range (IQR) 11-16.5). Median HIV-1 RNA viral load was 4.2 log 10 (IQR: 3.4-4.8). The primary end point was found in 11 children (69%), and 13 children (81%) had an HIV-1 RNA viral load <200 copies/ml. Median (IQR) for the baseline CD4 + cell count was 382 cells/μl (281-686 cells/μl), whereas after 48 wk of treatment with the new ART regimen, it was 640 cells/μl (361-936 cells/μl) (P < 0.001). conclusion: Darunavir/ritonavir, raltegravir, and etravirine were well tolerated in the present pediatric population. These drugs provide good options for children exposed to extensive ART. Regimens guided by genotyping data were effective for children who had ART failure and multidrug-resistant HIV-1 infection.i nfants and children who were infected perinatally are now surviving to adulthood with lifelong HIV infection and longterm exposure to combined antiretroviral therapy (ART) (1). Data from the United Kingdom Collaborative HIV Pediatric Study cohort demonstrated that over one-third of children had experienced virological treatment failure and were on a second or subsequent line of therapy at the time of their transition to adult care (2). In the pediatric setting, virological treatment failure occurs most frequently because of poor adherence to ART, and whenever viral replication is inefficiently controlled, virological treatment failure occurs more quickly, allowing the selection of HIV-1 quasispecies resistant to antiretroviral (ARV) drugs (3).Many innate and external factors have been associated with HIV drug resistance mutations in children, such as being infected perinatally, and extremely high viral load during the first steps of the infection, which can take longer to suppress than that in older children or adults, even when they are on fully active ART regimens (4).Interpretation of resistance tests in this context can be complex, particularly in the presence of expanding options for ARV drugs, and treatment decisions should be made with the support of pharmacists and clinicians who have expertise in the field (5).Currently, more than 20 different ARV drugs with six different classes of action have been approved for use in children or adolescents with HIV infection worldwide; most of them are used in Mexico (6).A good level of adherence is particularly difficult during adolescence, especially with a complex regimen ...

Effectiveness and safety of dolutegravir and raltegravir for treating children and adolescents living with HIV: a systematic review

“…One study (REALITY) included exclusively subjects on first‐line therapy, all of whom had CD4 counts <100 cells/μl at baseline [ 34 ]. Of note, four studies included populations where most were heavily pre‐treated (median of ≥3 lines of previous therapy) at start of raltegravir [ 35 , 36 , 39 , 41 , 43 ], while in a fifth study, raltegravir was used as part of a compassionate use programme for children who were virological non‐responders on previous regimens [ 38 ]. Eight studies included only subjects who were unsuppressed at baseline (Table 3 ).…”

“…Eight studies reported viral suppression data on 554 children (stratified into 13 sub‐populations) receiving raltegravir (Figure 3b ; File S2 , Table S2 )—one single‐arm trial and seven observational studies (Table 3 ) [ 17 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. There were limited data on raltegravir‐based first‐line therapy; in four children and adolescents in CHIPS [ 17 ], all achieved viral suppression at 48 weeks, while in infants with vertical transmission despite maternal/infant prophylaxis who had HIV RNA ≥1000 copies/ml at baseline (IMPAACT P1066), there was poor suppression (3/9, 33% at 24 weeks) [ 42 ].…”

“…Most of the raltegravir data were for populations on second‐ or subsequent‐line of therapy: one single‐arm trial [ 35 , 42 , 43 ] and seven observational studies [ 17 , 36 , 37 , 38 , 39 , 40 , 41 ]. At 1 year follow‐up, viral suppression ranged from 42% (5/12) to 83% (44/53) [ 17 , 41 ].…”

“…Six studies (one RCT, one single‐arm trial and four observational studies) reported on mortality in subjects on raltegravir (Figure 4 ) [ 34 , 35 , 36 , 38 , 39 , 41 , 42 , 43 ]. The REALITY trial reported mortality data for children and adolescents on a first‐line raltegravir‐intensified regimen (nevirapine or efavirenz‐based regimen, plus raltegravir) for 12 weeks with 24 weeks of follow‐up [ 34 ].…”

Adesão a terapia antiretroviral de crianças e adolescentes vivendo com HIV

“…Quando há falha na regularidade e no horário de tomar os medicamentos, a pressão que a droga exerce sobre o vírus é diminuída favorecendo o aparecimento de mutações de resistência. As cepas virais resistentes passam a não responder ao tratamento instituído, restringindo o arsenal terapêutico capaz de conter a infecção, agravando o problema existente 23,24 . Conclui-se que a adesão à TARV é melhor entre crianças que entre adolescentes provavelmente devido a adolescência ser um período crítico da TARV para o HIV.…”