Tanakorn Apornpong1, Beatriz Grinsztejn2, Michael Hughes3, Justin Ritz3, Stephen J Kerr1,4,5, Courtney V Fletcher6, Kiat Ruxrungtham1,7, Catherine Godfrey8, Robert Gross9, Evelyn Hogg10, Carole L Wallis11, Sharlaa Badal-Faesen12, Mina C Hosseinipour13, Rosie Mngqbisa14, Breno R Santos15, Sarita Shah16, Laura J Hovind17, Sajeeda Mawlana15, Marije Van Schalkwyk18, Nuntisa Chotirosniramit19, Cecilia Kanyama13, Nagalingeswaran Kumarasamy20, Robert Salata21, Ann C Collier22, Monica Gandhi23. 1. HIV-NAT, TRCARC, Bangkok, Thailand. 2. Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil. 3. Harvard T.H. Chan School of Public Health, Boston, Maryland, USA. 4. Biostatistics Excellence Centre, Bangkok, Thailand. 5. The Kirby Institute, UNSW, Sydney, Australia. 6. University of Nebraska Medical Center, Omaha, Nebraska, USA. 7. Chulalongkorn University, Bangkok, Thailand. 8. Division of AIDS NIAID, NIH, Bethesda, Maryland. 9. University of Pennsylvania, Pennsylvania. 10. Social & Scientific Systems, Silver Spring, Maryland, USA. 11. BARC-SA and Lancet Laboratories, Johannesburg. 12. Clinical HIV Research Unit, Helen Joseph Hospital, University of the Witwatersrand, Johannesburg, South Africa. 13. Kamuzu Central Hospital, Lilongwe, Malawi. 14. Durban International CRS, Durban, South Africa. 15. Hospital Nossa Senhora da Conceicao CRS, Rio Grande do Sul, Brazil. 16. Emory University, Atlanta, Georgia. 17. Frontier Science & Technology Research Foundation, Inc., Amherst, Massachusetts, USA. 18. Family Centre for Research with Ubuntu (FAMCRU), Stellenbosch University, Cape Town, South Africa. 19. Research Institute for Health Sciences, Chiang Mai, Thailand. 20. CART, Clinical Research Site, VHS Infection Disease Medical Centre, Chennai, India. 21. Case Western Reserve University, Cleveland, Ohio. 22. University of Washington, Seattle, Washington. 23. University of California, San Francisco, California, USA.
Abstract
OBJECTIVE: To evaluate associations between hair antiretroviral hair concentrations as an objective, cumulative adherence metric, with self-reported adherence and virologic outcomes. DESIGN: Analysis of cohort A of the ACTG-A5288 study. These patients in resource-limited settings were failing second-line protease inhibitor-based antiretroviral therapy (ART) but were susceptible to at least one nucleoside reverse transcriptase inhibitor (NRTI) and their protease inhibitor, and continued taking their protease inhibitor-based regimen. METHODS: Antiretroviral hair concentrations in participants taking two NRTIs with boosted atazanavir (n = 69) or lopinavir (n = 112) were analyzed at weeks 12, 24, 36 and 48 using liquid-chromatography--tandem-mass-spectrometry assays. Participants' self-reported percentage of doses taken in the previous month; virologic failure was confirmed HIV-1 RNA at least 1000 copies/ml at week 24 or 48. RESULTS: From 181 participants with hair samples (61% women, median age: 39 years; CD4+ cell count: 167 cells/μl; HIV-1 RNA: 18 648 copies/ml), 91 (50%) experienced virologic failure at either visit. At 24 weeks, median hair concentrations were 2.95 [interquartile range (IQR) 0.49-4.60] ng/mg for atazanavir, 2.64 (IQR 0.73--7.16) for lopinavir, and 0.44 (IQR 0.11--0.76) for ritonavir. Plasma HIV-1 RNA demonstrated inverse correlations with hair levels (rs -0.46 to -0.74) at weeks 24 and 48. Weaker associations were seen with self-reported adherence (rs -0.03 to -0.24). Decreasing hair concentrations were significantly associated with virologic failure, the hazard ratio (95% CI) for ATV, LPV, and RTV were 0.69 (0.56-0.86), 0.77 (0.68-0.87), and 0.12 (0.06-0.27), respectively. CONCLUSION: Protease inhibitor hair concentrations showed stronger associations with subsequent virologic outcomes than self-reported adherence in this cohort. Hair adherence measures could identify individuals at risk of second-line treatment failure in need of interventions.
OBJECTIVE: To evaluate associations between hair antiretroviral hair concentrations as an objective, cumulative adherence metric, with self-reported adherence and virologic outcomes. DESIGN: Analysis of cohort A of the ACTG-A5288 study. These patients in resource-limited settings were failing second-line protease inhibitor-based antiretroviral therapy (ART) but were susceptible to at least one nucleoside reverse transcriptase inhibitor (NRTI) and their protease inhibitor, and continued taking their protease inhibitor-based regimen. METHODS: Antiretroviral hair concentrations in participants taking two NRTIs with boosted atazanavir (n = 69) or lopinavir (n = 112) were analyzed at weeks 12, 24, 36 and 48 using liquid-chromatography--tandem-mass-spectrometry assays. Participants' self-reported percentage of doses taken in the previous month; virologic failure was confirmed HIV-1 RNA at least 1000 copies/ml at week 24 or 48. RESULTS: From 181 participants with hair samples (61% women, median age: 39 years; CD4+ cell count: 167 cells/μl; HIV-1 RNA: 18 648 copies/ml), 91 (50%) experienced virologic failure at either visit. At 24 weeks, median hair concentrations were 2.95 [interquartile range (IQR) 0.49-4.60] ng/mg for atazanavir, 2.64 (IQR 0.73--7.16) for lopinavir, and 0.44 (IQR 0.11--0.76) for ritonavir. Plasma HIV-1 RNA demonstrated inverse correlations with hair levels (rs -0.46 to -0.74) at weeks 24 and 48. Weaker associations were seen with self-reported adherence (rs -0.03 to -0.24). Decreasing hair concentrations were significantly associated with virologic failure, the hazard ratio (95% CI) for ATV, LPV, and RTV were 0.69 (0.56-0.86), 0.77 (0.68-0.87), and 0.12 (0.06-0.27), respectively. CONCLUSION: Protease inhibitor hair concentrations showed stronger associations with subsequent virologic outcomes than self-reported adherence in this cohort. Hair adherence measures could identify individuals at risk of second-line treatment failure in need of interventions.
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