Long-term virological outcome in children receiving first-line antiretroviral therapy

AIDS Research and Therapy

Ramalingam Srinivasan¹  Karunaianantham Ramesh¹  Sudha Subramanyan¹  Luke E. Hanna¹  Padmapriyadarsini Chandrasekaran¹  Navaneethan Poornagangadevi¹  Chockalingam Chandrasekar²  Soumya Swaminathan³  G. N. Sanjeeva⁴  Elumalai Suresh⁵  Anita Shet⁶  Bindu Gopalan⁷  Suba Sunderesan⁷  Christine Wanke⁸ 

[1]Department of Clinic Research, ICMR-National Institute for Research in Tuberculosis

[2]Government Hospital of Thoracic Medicine

[3]Indian Council of Medical Research

[4]Indira Gandhi Institute of Child Health

[5]Institute of Child Health and Government Hospital for Children

[6]Johns Hopkins Bloomberg School of Public Health

[7]St Johns Research Institute

[8]Tufts University School of Medicine

关键词: Antiretroviral therapy;    Pediatrics;    First-line;    Treatment outcome;    Viral load;   

DOI  :  10.1186/s12981-018-0208-9

来源: DOAJ

【 摘 要 】

Abstract Background Studies relating to long-term virological outcomes among children on first-line antiretroviral therapy (ART) from low and middle-income countries are limited. Methods Perinatally HIV infected, ART-naive children, between 2 and 12 years of age, initiating NNRTI-based ART during 2010–2015, with at least 12 months of follow-up, were included in the analysis. CD4 cell counts and plasma HIV-1 RNA were measured every 24 weeks post-ART initiation. Immunologic failure was defined as a decrease in the CD4 count to pre-therapy levels or below and virologic failure as HIV-RNA of > 1000 copies/ml at 48 weeks after ART initiation. Genotypic resistance testing was performed for children with virologic failure. Logistic regression analysis was done to identify predictors of virologic failure. Results Three hundred and ninety-three ART-naïve children living with HIV [mean (SD) age: 7.6 (3) years; mean (SD) CD4%: 16% (8); median (IQR) HIV-RNA: 5.1 (3.5–5.7) log10 copies/ml] were enrolled into the study. At 48 weeks, significant improvement occurred in weight-for-age and height-for-age z-scores from baseline (all p < 0.001). The immunologic response was good; almost 90% of children showing an increase in their absolute CD4+ T cell count to more than 350 cells/mm3. Immunological failure was noted among 11% (28/261) and virologic failure in 29% (94/328) of children. Of the 94 children with virologic failure at 12 months, 36 children showed immunologic failure while the rest had good immunologic improvement. There was no demonstrable correlation between virologic and immunologic failure. 62% had reported > 90% adherence to ART. At the time of virologic failure, multiple NNRTI-associated mutations were observed: 80%—K103N and Y181C being the major NNRTI mutations—observed. Sensitivity (95% CI) of immunologic failure to detect virologic failure was 7% (2–12), specificity 97% (92.4–98.9), PPV 44% (13.7–78.8) and NPV was 72% (65–77.9). There were no statistically significant predictors to detect children who will develop virologic failure on treatment. Conclusions Considerable immunological improvement is seen in children with ART initiation, but may not be an effective tool to monitor treatment response in the long-term. There is a lack of correlation between immunologic and virologic response while on ART, which may lead to a delay in identifying treatment failures. Periodic viral load monitoring is, therefore, a priority.

【 授权许可】

Unknown