Non-Nucleoside Reverse Transcriptase Inhibitor–Based Antiretroviral Therapy in Perinatally HIV-Infected, Treatment-Naïve Adolescents in Asia

Abstract

Purpose About a third of untreated, perinatally HIV-infected children reach adolescence. We evaluated the durability and effectiveness of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in this population. Methods Data from perinatally HIV-infected, antiretroviral-naïve patients initiated on NNRTI-based ART aged 10–19 years who had ≥6 months of follow-up were analyzed. Competing risk regression was used to assess predictors of NNRTI substitution and clinical failure (WHO stage 3/4 event or death). Viral suppression was defined as a viral load <400 copies/ml. Results Data from 534 adolescents met our inclusion criteria (56.2% female; median age at treatment initiation 11.8 years). After five years of treatment, median height-for-age z-score increased from −2.3 to −1.6 and median CD4+ cell count increased from 131 to 580 cells/mm3. The proportion of patients with viral suppression after 6 months was 87.6% and remained >80% up to five years of follow-up. NNRTI substitution and clinical failure occurred at rates of 4.9 and 1.4 events per 100 patient-years, respectively. Not using cotrimoxazole prophylaxis at ART initiation was associated with NNRTI substitution (HR 1.5 versus using, 95%CI 1.0–2.2, p=0.05). Baseline CD4+ count ≤200 cells/mm3 (HR 3.3 versus >200, 95%CI 1.2–8.9, p=0.02) and not using cotrimoxazole prophylaxis at ART initiation (HR 2.1 versus using, 95%CI 1.0–4.6, p=0.05) were both associated with clinical failure. Conclusions Despite late ART initiation, adolescents achieved good rates of catch-up growth, CD4+ count recovery, and virological suppression. Earlier ART initiation and routine cotrimoxazole prophylaxis in this population may help to reduce current rates of NNRTI substitution and clinical failure.

Immuno-virological response and associated factors amongst HIV-1 vertically infected adolescents in Yaoundé-Cameroon

“…After a median of seven years of ART, ALWHIV could still be on a successful first-line regimen in RLS like Cameroon. With the median age of 13 years in a population apparently asymptomatic, these findings also demonstrate the benefits of ART amongst ALWHIV, and advocate for strategies toward improved management [ 12 – 14 ].…”

Choice of initial antiretroviral drugs and treatment outcomes among HIV-infected patients in sub-Saharan Africa: systematic review and meta-analysis of observational studies

“…A study done on comparison between NVP and lopinavir-ritonavir [ 36 ] was excluded as it was not the interest of this review. Other six papers were excluded as the studies were conducted among children [ 37 ], conducted outside of sub-Saharan Africa, [ 38 , 39 , 40 , 41 ], and systematic reviews and meta-analysis articles [ 20 ] were. Subsequently, of 79 full record articles, a total of 36 were eligible studies.…”

Growth and pubertal development in HIV-infected adolescents

“…Substantial increases in WAZ at ART initiation over time were observed among children in Central Africa, with mean z-scores increasing from −2.2 in 2004–2005 to −1.4 in 2012–2013 [24]; the percent underweight decreased from 56% to 36% over this period. However, it should be noted that younger children (<10 years) comprise the majority of the populations in the studies described above, and several studies which report growth measures specifically for adolescents (age 10–19) have identified more severe growth deficits than among younger children [17,19].…”

“…Among Chinese HIV-infected youth, a 2-year increase of about 0.4 in both HAZ and WAZ was observed, with corresponding decreases in prevalence of stunting from 42% to 34% and in underweight from 21% to 13% [18]. After 5 years on ART, adolescents in the TREAT Asia Pediatric HIV Observational Database (TApHOD) achieved increases in HAZ from −2.3 to −1.6 [17]. Similar improvement was observed in both HAZ and WAZ by 4 years after ART initiation among South African and West African youth [12] (see Table 2).…”

“…Mixed findings of catch-up growth by sex have been reported [18,20]. Multiple studies have observed that lower initial HAZ was a strong predictor of failure to achieve growth recovery [17,19 20…”