Virological Response and Resistance Profiles After 18 to 30 Months of First- or Second-/Third-Line Antiretroviral Treatment: A Cross-Sectional Evaluation in HIV Type 1-Infected Children Living in the Central African Republic

Abstract

A total of 242 HIV-1-infected children were followed up at the Complexe Pédiatrique of Bangui, Central African Republic, including 165 receiving antiretroviral treatment in first- (n=150) or second-/third-line (n=15) regimens. They were prospectively included in a study, in 2009, to assess their virological status and prevalence of antiretroviral drug-resistance mutations in cases of virological failure, according to revised 2010 WHO criteria (e.g., HIV-1 RNA >3.7 log(10) copies/ml). Detectable plasma HIV-1 RNA was observed in 53% of children under first-line treatment, and virological failure was diagnosed in 40%, which was associated in 85% of cases with viruses harboring at least one drug-resistance mutation to nucleoside reverse transcriptase inhibitors (NRTI) or nonnucleoside reverse transcriptase inhibitors (NNRTI), and in 36% of cases with at least one major drug-resistance mutation to NRTI or NNRTI when excluding the M184V mutation. Overall, the proportion of children receiving a first-line regimen for a median of 18 months with virological failure associated with drug-resistance mutations, and thus eligible for a second-line treatment, was estimated at 34% of the whole cohort. In children under second-/third-line therapy, virological failure occurred in 47%, plus at least one major drug-resistance mutation to NRTI or NNRTI, though less commonly to protease inhibitors. Taken together, these findings argue in favor of the urgent need to improve distribution of pediatric antiretroviral drugs in the Central African Republic, to increase adherence by treated children, and to offer adequate HIV biological monitoring.

Short Communication: High Rates of Thymidine Analogue Mutations and Dual-Class Resistance Among HIV-Infected Ugandan Children Failing First-Line Antiretroviral Therapy

“…The rate of TAMs detected in our study is very high compared to previous reports among children in resource-limited settings where, as in Uganda, NNRTI-based first-line regimens are standard. 8,[20][21][22][23] This may be attributed to the fact that over half of children had a longer duration of treatment failure (i.e., longer than 1 month). Possibly, this reflects clinicians' reluctance to switch to second-line ART, due to regimen cost and subsequent loss of drug options.…”

Tackling virological failure in HIV-infected children living in Africa

“…A better response to second-line treatment occurs when the patient resistance profile is known before switching therapy [100]. Studies show a high rate (96.5%) of NRTI and NNRTI (98.6%) resistanceassociated mutations [100] in children failing first-line treatment in Uganda; similarly, in another study, a high rate of NNRTI (95%) and NRTI (98%) resistance-associated mutations were also observed [101] with the proportion of TAMs much higher than reported among children in other African countries [84,[102][103][104].…”

High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic

“…[10,11] Various factors are involved in the fact that HIV-infected children and adolescents are more vulnerable than adults to virological failure and drug resistance including the HIV resistance risk during prevention of mother-to-child transmission, [12] frequently high HIV-1 RNA plasma level in children, [13] limited number of available pediatric-formulated antiretroviral drugs for the different age classes, variable pharmacokinetics, rapid changes in body weight, frequently observed poor adherence, social environment, psychosocial factors, and frequent absence of biological monitoring. [8,14–25] Thus, recent studies in African children receiving 1st-line antiretroviral treatment according to the treatment guidelines of the World Health Organization (WHO) for resource-limited countries have reported generally high degrees of virological failure depending in part on treatment duration, ranging from 6% in Kwazulu-Natal (South Africa), [26,27] 15% in Cape Town (South Africa), [28] 17% [29] to 44% [30] in Ghana, 26% in Uganda, [31] 29% in Rwanda, [32] 34% in Kenya, [33] 35% in Ivory Coast, [16] 40% in the Central African Republic, [23] 53% in rural Cameroon, [34] 55% in Senegal, [24] 56% in Togo, [25] 58% in Tanzania [35,36] to 61% in Mali. [37] In addition, circulating virus resistant to at least 1 antiretroviral drug could be detected very frequently in 61% [33] to 98% [38] of children with a detectable viral load while receiving antiretroviral treatment.…”

“…[9] Finally, several studies have reported on the outcome of antiretroviral treatment in children in Africa, but only a few reports are available on long-term outcomes and in adolescents. [19,23–25,35,37,39,40] …”

“…[41–43] To evaluate the management of pediatric AIDS, an observational cohort of HIV-infected children was followed-up since 2007 in the “ Complexe Pédiatrique” of Bangui, the main health care clinic for HIV-infected children of the Central African Republic. [21,23] In 2009, Charpentier and colleagues [23] reported that one-third (34%) of children receiving 1st-line regimen (median of treatment = 18 months) was in virological failure with selection of drug resistance mutations (DRMs), and therefore eligible to 2nd-line treatment. In children under 2nd-line therapy, virological failure appeared more prevalent (47%), and the selection of at least 1 major DRM to nucleosidic reverse transcriptase inhibitor (NRTI) or non-nucleosidic reverse transcriptase inhibitor (NNRTI), and less frequently to protease inhibitor (PI).…”