Tackling virological failure in HIV-infected children living in Africa

Abstract

Drug resistance in HIV-infected children is one of the main contributors to antiretroviral treatment (ART) failure, especially in developing countries. Sub-Saharan Africa has the largest burden of pediatric HIV infection in the world. Herein, we systematically review the current status of ART failure in HIV-infected African children. A literature search for publications within 10 years was performed through PubMed to identify relevant articles. Included studies examined the impact of timing of ART initiation, criteria for diagnosing therapeutic failure, predictors of therapeutic failure, management strategies and future directions to minimize failure rates in these pediatric populations. Although there is scale-up of ART programs in Africa, novel therapeutic and management strategies are needed to overcome current challenges.

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

“…The impact of DRMs acquired via prevention of mother-to-child transmission could not be evaluated in our study, but we previously reported a moderate (between 5% and 15%) prevalence of DRMs in the Central African HIV-infected pediatric population of Bangui. [96] These observations support the use of lopinavir-based 1st-line regimens in children in Africa as recommended by the WHO, [7,8,46,82,85,90,97] especially with the recent national recommendations to implement lifelong antiretroviral treatment for mothers. However, only 1 (12.5%) of the 8 children aged below 5 years was on a 1st-line PI-based antiretroviral treatment regimen in 2013 as recommended by the WHO, illustrating that these guidelines have not yet been implemented.…”

“…During the last decade, the use of antiretroviral drugs was widespread in sub-Saharan Africa for preventing mother-to-child transmission, dramatically reversed the spread of HIV and significantly reduced the morbidity and mortality of this epidemic in the child population. [4–8] However, compared to adults, children living with HIV are less likely to receive antiretroviral treatment. [9] Furthermore, if the extension of access to antiretroviral drugs in African children has significantly reversed the infant mortality curve associated with AIDS, it has also facilitated emergence and spread of drug-resistant virus in sub-Saharan Africa.…”

“…[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.…”

Point-of-care viral load testing among adolescents and youth living with HIV in Haiti: a protocol for a randomised trial to evaluate implementation and effect

“…A high VL among a patient with perfect adherence may indicate potential drug resistance. [11][12][13] Returning and discussing VL results with patients has been shown to be a tool to support viral resuppression since it provides an opportunity for providers to reinforce adherence. [14][15][16] Since adolescents will require treatment for years longer than adults, poor adherence, treatment failure and drug resistance can have more serious consequences making VL monitoring particularly important for this population.…”

Impact of lopinavir-ritonavir exposure in HIV-1 infected children and adolescents in Madrid, Spain during 2000-2014

“…Treatment efficacy is compromised by an inappropriate adherence to treatment and by the selection of resistant virus [5]. Since approximately one-third of HIV-infected children experience virological failure within two years of initiating cART [6], drug resistance mutation (DRM) monitoring should be performed at diagnosis and after therapy failure to optimize first and second or more-line regimens. However, resistance studies in paediatric infections worldwide are still scarce [7].…”