High virological failure rates in HIV-1 perinatally infected children in South Africa: A retrospective cohort study

Abstract

The rapid scale-up of global HIV antiretroviral therapy (ART) in resource-limited settings has resulted in the successful enrolment of millions of HIV-infected children into care and treatment programmes. [1] South Africa (SA) has made great strides in HIV treatment, and has the largest ART programme in the world, with ~4.4 million people receiving ART. [2] The scale-up of ART has resulted in improvements in virological and immunological parameters, as well as reductions in mortality, morbidity and comorbidities. [3,4] However, viral load rebound may still occur in some patients, despite an initial good response to ART. Maintenance of maximal and durable suppression of plasma viraemia has been particularly challenging for HIV-infected children, and nonadherence is often the strongest predictor of failure to achieve viral suppression. [5-7] The challenges that limit high adherence in children include complex ART regimens, significant side-effects, limited availability of paediatric formulations, the lifelong duration ART, and dependence on a caregiver to administer the medication. [8-10] A systematic review of resistance data in children from developing world settings found that 90% of those failing first-line regimens had at least one detectable resistance mutation. [11] Virological failure rates of up to 50% have been reported in African children during the 12-24 months after ART initiation. [12-14] Studies that include long-term follow-up of children on combination ART (cART) are limited; it is therefore difficult to generate reliable estimates of the incidence of first-line failure in large paediatric cohorts in public sector settings and to identify the factors associated with virological failure. We therefore analysed data from a large cohort of HIV-positive children and adolescents receiving care in one of the largest public sector ART programmes in SA to estimate the cumulative incidence of virological failure, identify the determinants of virological failure, and evaluate the emergence of drug resistance. Methods Study population A retrospective cohort study of HIV-1 perinatally infected children was conducted at the Dr George Mukhari Academic Hospital (DGMAH) in Pretoria, SA. Patients included in the study were aged <17 years, initiated first-line ART between 1 January 2004 and 31 December 2013, and had at least 5 years of HIV viral load measurements. Longitudinal clinical and demographic data were collected from the clinical files until last follow-up review or up to a 5-year time point following the initiation of ART. Failure to achieve an HIV viral load below the limit of detection was assessed at multiple time points during a 5-year period. For the purposes of this study, virological failure was defined as a viral load of >1 000 copies/ mL 1 year after ART initiation. HIV drug resistance HIV genotyping was performed using an in-house drug resistance assay. Briefly, a 1.7 kb amplicon was generated by reverse transcriptase (RT)-initiated polymerase chain reaction of the entire protease (PR) and partial...

Virological failure of first-line antiretroviral therapy in children living with HIV in Indonesia and associated factors

“…The incidence density of treatment failure in our study was 3.3 children per 1,000 person-months, which was higher compared to that in a South African study reporting an incidence density of 18.7 per 100 person-years (equivalent to 1.5 per 1,000 personmonths). 15 The mean time from first-line therapy to virological failure was 29 months in our study, similar to that of 30 months reported by an Ethiopian study. 17 For the last 15 years in Indonesia, ARV backbone regimens have been limited to nevirapine and efavirenz; both of which were reported to be ineffective among African populations with high perinatal exposure.…”

“…17 For the last 15 years in Indonesia, ARV backbone regimens have been limited to nevirapine and efavirenz; both of which were reported to be ineffective among African populations with high perinatal exposure. 15 However, exposure risk was not a determinant of virological failure in our study, since almost all subjects had missed perinatal prevention. In subjects treated with nevirapine, the proportion of failure was much higher compared to those treated with efavirenz, but still comparable to findings of other studies reporting virological failure.…”

“…26 Prevalence of virological failure in our study (45.8%) was higher than reported in three studies in Africa and one study in India. [12][13][14][15] This difference could have been due to follow-up periods and study settings. The follow-up time for our cohort was 6 months to 18 years, which was longer than in other studies.…”

“…We expected data to be missing in several variables. The minimum required sample size was determined using a single population proportion formula, with the following statistical assumptions: an incidence rate of 1.5 per person months based on a study by Makatini et al 15 in South Africa, a margin of error of 5%, and a Za/2 of 1.96, which was the corresponded to a 95% confidence interval (95%CI). Precision was determined at 1% and time of observation (T) was 216 months, resulting in a minimum sample size of 267 subjects.…”

“…[12][13][14] In South Africa, the incidence rate of virological failure was 18.7 per 100 person years follow up, while India, as Asia's representative, reported a 29% prevalence of viral failure. 9,15 Several factors that are known to increase the risk of virological failure on CLHIV include younger age at diagnosis or treatment initiation, WHO stage 3 and 4, lower CD4 count, nevirapine (NVP)-based regimen, and treatment interruption. 10,11,[16][17][18][19][20][21] This study aimed to determine the incidence of treatment failure with first-line ART in situations of limited VL monitoring in Indonesia, as well as to identify the predictors of treatment failure in order to assist clinicians in monitoring their patients more closely.…”