Brief Report: Lopinavir Hair Concentrations Are the Strongest Predictor of Viremia in HIV-Infected Asian Children and Adolescents on Second-Line Antiretroviral Therapy

Abstract

Background Children/adolescents display suboptimal antiretroviral therapy (ART) adherence and outcomes versus adults. Hair ART concentrations are objective adherence measures that predict viremia in adults but longitudinal data on hair levels in pediatric populations is limited. We assessed the predictive utility of hair lopinavir levels on viremia among youth on second-line ART. Methods We examined predictors of viremia (HIV-1 RNA >400 and >1000 copies/ml) at least 24 weeks after switch to lopinavir-based second-line ART in a cohort of HIV-infected Asian children followed between 2011 and 2014. Small hair samples, HIV-1 RNA, and self-reported adherence were collected biannually. Hair concentrations of lopinavir were measured via liquid-chromatography/tandem-mass-spectrometry using validated methods. Time-to-first viremia was examined using discrete-time Cox models. Results Overall, 244 children met inclusion criteria for the present analysis. Approximately half (55%) were males and the median age 10 years (interquartile range [IQR] 7–13); 40% were >11 years. At switch to second-line ART, median CD4 count was 300 (IQR 146–547) cells/mm3 and median HIV-RNA level was 5.0 (IQR 4.3–5.6) log10/mL. Median time of study follow-up was 48 weeks and a median of 3 (range 1–5) hair samples collected from each participant. Adjusting for age, sex, country, self-reported adherence, CD4, and HIV-RNA, higher lopinavir hair concentrations were the strongest predictor of lower odds of viremia (HIV-RNA >400 copies/ml adjusted odds ratio [aOR]=0.41 per doubling in hair concentration, 95% 0.29–0.58, p<0.001; HIV-RNA >1000 copies/ml aOR=0.54, 95% CI 0.45–0.65, p<0.001). Conclusions Hair concentrations predict viremia among children with HIV on 2nd-line ART and could guide clinical decisions for this population.

Association of Hair Concentrations of Antiretrovirals with Virologic Outcomes Among People Living with HIV in Guangxi, China

“… 25–27 Interestingly, our study revealed that hair concentrations of 3TC and EFV, but not AZT, are the strongest independent predictor of virologic suppression. Our findings of hair concentrations of 3TC and EFV added evidence to existing studies that reported that hair concentrations of antiretrovirals (eg, TFV, 33 EFV, 43 , 45 NVP, 30 LPV, 31 , 32 , 34 ATV 28 , 34 ) were the strongest independent predictor of virologic suppression. Regarding the nonsignificant finding of hair AZT concentrations, the small sample size and lower hair AZT concentrations could contribute to this finding.…”

“…Furthermore, the simultaneous determination of hair concentrations of antiretrovirals in multiple classes is technically possible. [21][22][23][24] However, major of the previous studies only investigated the association of hair concentrations of a single antiretroviral 13,[25][26][27][28][29][30][31][32][33] or antiretrovirals in a single class 34 with virologic outcomes. Limited data are available on the association of hair concentrations of antiretrovirals in multiple classes with virologic outcomes.…”

LC-MS/MS Quantification of Nevirapine and Its Metabolites in Hair for Assessing Long-Term Adherence

“…As far as we know, this was the first successful attempt to determine 2-OH NVP and 3-OH NVP and evaluate long-term adherence based on the concentrations of metabolites in human hair. Previous studies were limited to the detection of NVP metabolites in other biological samples, such as human serum [28] and for the adherence evaluation based on drug prototypes in hair [22][23][24][25]. Additionally, we found that NVP's metabolites showed high consistency with NVP in evaluating long-term adherence.…”

“…Existing studies utilize the concentrations of the drugs' prototype in hair to evaluate long-term adherence [22][23][24][25]. However, the antiretroviral drugs are mostly metabolized in the circulating system once orally administered and only a fraction of them remain as the prototype structure.…”

Tenofovir and emtricitabine concentrations in hair are comparable between individuals on tenofovir disoproxil fumarate versus tenofovir alafenamide‐based ART

“…The University of California San Francisco‐Hair Analytical Laboratory (UCSF‐HAL) has quantified a number of ARVs in hair (e.g., atazanavir, 19 lopinavir, 20 ritonavir, 20 efavirenz, 20 nevirapine, 21 darunavir, raltegravir, dolutegravir, TFV/FTC, 22–29 ) for research projects over the past 15 years. Hair concentrations of ARVs have been shown to be strong predictors of virologic response for a variety of ARVs, including TFV/FTC 30–41 …”