Adherence and Viral Suppression Among Infants and Young Children Initiating Protease Inhibitor-based Antiretroviral Therapy

Overview

Journal Pediatr Infect Dis J

Specialty Pediatrics

Date 2012 Dec 20

PMID 23249913

Citations 13

Authors

Chloe A Teasdale

Elaine J Abrams

Ashraf Coovadia

Renate Strehlau

Leigh Martens

Louise Kuhn

Affiliations

Soon will be listed here.

Abstract

Background: High levels of adherence to antiretroviral therapy are considered necessary to achieve viral suppression. We analyzed data from a cohort of HIV-infected children who were <2 years of age receiving protease inhibitor-based antiretroviral therapy to investigate associations between viral suppression and adherence ascertained using different methods.

Methods: Data were from the prerandomization phase of a clinical trial in South Africa of HIV-infected children initiating either ritonavir-boosted lopinavir (LPV/r) or ritonavir-based antiretroviral therapy. At scheduled visits during the first 24 weeks of enrollment, study pharmacists measured quantities of medications returned to the clinic. Caregivers answered questionnaires on missed doses and adherence barriers. Associations between adherence and viral suppression (HIV-1 RNA <400 copies/mL) were investigated by regimen.

Results: By 24 weeks, 197 of the 269 (73%) children achieved viral suppression. There was no association between viral suppression and caregiver reported missed doses or adherence barriers. For children receiving the LPV/r-based regimen, medication return adherence to each of the 3 drugs in the regimen (LPV/r, lamivudine or stavudine) individually or together was associated with viral suppression at different adherence thresholds. For example, <85% adherence to any of the 3 medications significantly increased odds of lack of viral suppression (odds ratio: 2.30, 95% confidence interval: 1.30-4.07, P = 0.004). In contrast, for children receiving the ritonavir-based regimen, there was no consistent pattern of association between medication return and viral suppression.

Conclusions: Caregiver reports of missed doses did not predict virologic response to treatment. Pharmacist medication reconciliation correlated strongly with virologic response for children taking a LPV/r-based regimen and appears to be a valid method for measuring pediatric adherence.

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References

Gross R, Yip B, Lo Re 3rd V, Wood E, Alexander C, Harrigan P . A simple, dynamic measure of antiretroviral therapy adherence predicts failure to maintain HIV-1 suppression. J Infect Dis. 2006; 194(8):1108-14. DOI: 10.1086/507680. View

Patel K, Hernan M, Williams P, Seeger J, McIntosh K, Van Dyke R . Long-term effectiveness of highly active antiretroviral therapy on the survival of children and adolescents with HIV infection: a 10-year follow-up study. Clin Infect Dis. 2008; 46(4):507-15. DOI: 10.1086/526524. View

Farley J, Montepiedra G, Storm D, Sirois P, Malee K, Garvie P . Assessment of adherence to antiretroviral therapy in perinatally HIV-infected children and youth using self-report measures and pill count. J Dev Behav Pediatr. 2008; 29(5):377-84. PMC: 6677401. DOI: 10.1097/DBP.0b013e3181856d22. View

Chesney M, Ickovics J, Chambers D, Gifford A, Neidig J, Zwickl B . Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: the AACTG adherence instruments. Patient Care Committee & Adherence Working Group of the Outcomes Committee of the Adult AIDS Clinical Trials Group.... AIDS Care. 2000; 12(3):255-66. DOI: 10.1080/09540120050042891. View

Haberer J, Cook A, Walker A, Ngambi M, Ferrier A, Mulenga V . Excellent adherence to antiretrovirals in HIV+ Zambian children is compromised by disrupted routine, HIV nondisclosure, and paradoxical income effects. PLoS One. 2011; 6(4):e18505. PMC: 3080873. DOI: 10.1371/journal.pone.0018505. View

Coovadia A, Abrams E, Stehlau R, Meyers T, Martens L, Sherman G . Reuse of nevirapine in exposed HIV-infected children after protease inhibitor-based viral suppression: a randomized controlled trial. JAMA. 2010; 304(10):1082-90. PMC: 4540068. DOI: 10.1001/jama.2010.1278. View

Reitz C, Coovadia A, Ko S, Meyers T, Strehlau R, Sherman G . Initial response to protease-inhibitor-based antiretroviral therapy among children less than 2 years of age in South Africa: effect of cotreatment for tuberculosis. J Infect Dis. 2010; 201(8):1121-31. PMC: 2946637. DOI: 10.1086/651454. View

Persaud D, Ray S, Kajdas J, Ahonkhai A, Siberry G, Ferguson K . Slow human immunodeficiency virus type 1 evolution in viral reservoirs in infants treated with effective antiretroviral therapy. AIDS Res Hum Retroviruses. 2007; 23(3):381-90. DOI: 10.1089/aid.2006.0175. View

Taylor B, Hunt G, Abrams E, Coovadia A, Meyers T, Sherman G . Rapid development of antiretroviral drug resistance mutations in HIV-infected children less than two years of age initiating protease inhibitor-based therapy in South Africa. AIDS Res Hum Retroviruses. 2011; 27(9):945-56. PMC: 3161115. DOI: 10.1089/aid.2010.0205. View

10.

Chadwick E, Capparelli E, Yogev R, Pinto J, Robbins B, Rodman J . Pharmacokinetics, safety and efficacy of lopinavir/ritonavir in infants less than 6 months of age: 24 week results. AIDS. 2007; 22(2):249-55. DOI: 10.1097/QAD.0b013e3282f2be1d. View

11.

Lima V, Harrigan R, Murray M, Moore D, Wood E, Hogg R . Differential impact of adherence on long-term treatment response among naive HIV-infected individuals. AIDS. 2008; 22(17):2371-80. DOI: 10.1097/QAD.0b013e328315cdd3. View

12.

Davies M, Boulle A, Fakir T, Nuttall J, Eley B . Adherence to antiretroviral therapy in young children in Cape Town, South Africa, measured by medication return and caregiver self-report: a prospective cohort study. BMC Pediatr. 2008; 8:34. PMC: 2533648. DOI: 10.1186/1471-2431-8-34. View

13.

Kalichman S, Amaral C, Swetsze C, Eaton L, Kalichman M, Cherry C . Monthly unannounced pill counts for monitoring HIV treatment adherence: tests for self-monitoring and reactivity effects. HIV Clin Trials. 2011; 11(6):325-31. PMC: 7737540. DOI: 10.1310/hct1106-325. View

14.

Ciaranello A, Chang Y, Margulis A, Bernstein A, Bassett I, Losina E . Effectiveness of pediatric antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis. Clin Infect Dis. 2009; 49(12):1915-27. PMC: 2787758. DOI: 10.1086/648079. View

15.

Muller A, Bode S, Myer L, Stahl J, von Steinbuchel N . Predictors of adherence to antiretroviral treatment and therapeutic success among children in South Africa. AIDS Care. 2010; 23(2):129-38. DOI: 10.1080/09540121003758523. View

16.

Haberer J, Kiwanuka J, Nansera D, Ragland K, Mellins C, Bangsberg D . Multiple measures reveal antiretroviral adherence successes and challenges in HIV-infected Ugandan children. PLoS One. 2012; 7(5):e36737. PMC: 3348916. DOI: 10.1371/journal.pone.0036737. View

17.

Kuhn L, Coovadia A, Strehlau R, Martens L, Hu C, Meyers T . Switching children previously exposed to nevirapine to nevirapine-based treatment after initial suppression with a protease-inhibitor-based regimen: long-term follow-up of a randomised, open-label trial. Lancet Infect Dis. 2012; 12(7):521-30. PMC: 4539971. DOI: 10.1016/S1473-3099(12)70051-8. View

18.

McIlleron H, Ren Y, Nuttall J, Fairlie L, Rabie H, Cotton M . Lopinavir exposure is insufficient in children given double doses of lopinavir/ritonavir during rifampicin-based treatment for tuberculosis. Antivir Ther. 2011; 16(3):417-21. DOI: 10.3851/IMP1757. View

19.

Nabukeera-Barungi N, Kalyesubula I, Kekitiinwa A, Byakika-Tusiime J, Musoke P . Adherence to antiretroviral therapy in children attending Mulago Hospital, Kampala. Ann Trop Paediatr. 2007; 27(2):123-31. DOI: 10.1179/146532807X192499. View

20.

Parienti J, Ragland K, Lucht F, de La Blanchardiere A, Dargere S, Yazdanpanah Y . Average adherence to boosted protease inhibitor therapy, rather than the pattern of missed doses, as a predictor of HIV RNA replication. Clin Infect Dis. 2010; 50(8):1192-7. PMC: 3591724. DOI: 10.1086/651419. View