Excellent retention, virologic and clinical outcomes after transitioning from an antiretroviral treatment clinical trial to locally-provided care and treatment in Africa
Keywords:HIV, Antiretroviral therapy, Post clinical trial care, Resource limited settings
Background: Little is known about outcomes among clinical trial participants following completion of study-provided care and treatment in resource limited settings. We sought to describe outcomes among HIV clinical trial participants after transitioning to local routine care in Africa.
Methods: In the OCTANE study, 741 women with CD4 <200 cells/mm3 in 7 African countries were randomized to initiate antiretroviral treatment (ART) with tenofovir/emtricitabine (TDF/FTC) plus either lopinavir/ritonavir (LPV/r) or nevirapine (NVP). When study-specified ART ended (48-191 weeks after study entry), participants transitioned to locally-provided HIV care and non-study ART. Consenting participants were interviewed and had toxicity labs, CD4 and HIV-1 RNA testing, and clinical outcomes assessed at 12 and 72 weeks after transition to local care.
Results: Five hundred thirteen (77%) of the 669 women in follow-up at completion of the interventional trial participate in the extended follow-up. 513 women, 476 (93%) had HIV-1 RNA <400 cp/mL at time of transition, and 489 (95%) completed follow-up. Seventy-seven women (19%) had a total of 99 antiretroviral regimen changes during post-trial follow-up. 30% of the 99 regimen changes-were due to lack of local drug availability. Thirteen (3%) women had Grade ≥3 laboratory abnormalities and 3 experienced worsening of the WHO HIV stage. Two women died. Eighty-nine percent of 484 with results had HIV-1 RNA ≤400 cp/mL at 72 weeks after transition to local non-study HIV care and treatment.
Conclusions: The vast majority of women were able to continue key components of their ART and to maintain virologic suppression through 72 weeks of locally-provided post-study care.
Trial registration: ClinicalTrials.gov NCT00089505
Centers for Disease Control and Prevention MMWR Morbidity Mortality Weekly Report. Scale-up of HIV Viral Load Monitoring — Seven Sub-Saharan African Countries. Centers for Disease Control and Prevention MMWR Morbidity Mortality Weekly. 2015;64(46):
Holmes CB, Sanne I. Changing models of care to improve progression through the HIV treatment cascade in different populations. Curr Opin HIV AIDS. 2015;10:447–50.
Khabala KB, Edwards JK, Baruani B, Sirengo M, Musembi P, Kosgei RJ, et al. Medication Adherence Clubs: a potential solution to managing large numbers of stable patients with multiple chronic diseases in informal settlements. Trop Med Int Health. 2015;20(10):1265-70.
Brennan AT, Long L, Maskew M, Sanne I, Jaffray I, MacPhail P, et al. Outcomes of stable HIV-positive patients down-referred from a doctor-managed antiretroviral therapy clinic to a nurse-managed primary health clinic for monitoring and treatment. AIDS. 2011;25:2027–36.
Dawson L, Klingman K, Marrazzo J. Addressing standards of care in resource-limited settings J Acquir Immune Defic Syndr. 2014;65(1):10-4.
Pratt B, Zion D, Lwin KM, Cheah PY, Nosten F, Loff B. Ancillary Care: From Theory to Practice in Int Clin Res Public Health Ethics. 2013;6(2):154–69.
Sofaer N. Reciprocity-Based Reasons For Benefiting Research Participants: Most Fail, The Most Plausible Is Problematic. Bioethics. 2014;28(9):456-71.
Millum J. Post-trial Access to Antiretrovirals: Who Owes What to Whom? Bioethics. 201125(3):145–54.
Dawson L, Zwerski S. Clinical Trial Design For Hiv Prevention Research: Determining Standards Of Prevention. 2015;29(5):316-23.
Iserson KV, Biros MH, James HC. Challenges in International Medicine: Ethical Dilemmas, Unanticipated Consequences, and Accepting Limitations. Acad Emergency Med. 2012;19(6):683-92.
Pratt B, Loff B. A framework to link international clinical research to the promotion of justice in global health. Bioethics. 2014;28(8):387-96.
Godfrey C, Payton M, Tasker S, Proestel S, Schouten JT. Ensuring Participant Safety and Trial Integrity with Clinical Trials Oversight. J Acquir Immune Defic Syndr. 2014;65(1):40–3.
Lockman S, Hughes MD, McIntyre J, Zheng Y, Chipato T, Conradie F, et al. Antiretroviral therapies in women after single-dose nevirapine exposure. N Engl J Med. 2010;363(16):1499-509.
Lockman S, Hughes M, Sawe F, Zheng Y, McIntyre J, Chipato T, et al. Nevirapine- versus lopinavir/ritonavir-based initial therapy for HIV-1 infection among women in Africa: a randomized trial. PLoS Med. 2012;9(6):e1001236.
The Belmont Report. 1979. Available at http://www.hhs.gov/ohrp/ humansubjects/guidance /belmont.html. Accessed on 23 November 2016.
Maman D, Zeh C, Mukui I, Masson BKS, Opolo V, Szumilin E, et al. Cascade of HIV care and population viral suppression in a high-burden region of Kenya. AIDS. 2015;29:1557–65.
Fox MP, Rosen S. Patient retention in antiretroviral therapy. programs up to three years on treatment in sub-Saharan Africa, 2007–2009: systematic review. Trop Med Intl Health. 2010;15(1):1–15.
National AIDS and STI Control Programme (NASCOP), Kenya. Kenya AIDS Indicator Survey 2012: Final Report. Nairobi, NASCOP. 2014.