Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis

Andreas D Haas; Olivia Keiser; Eric Balestre; Steve Brown; Emmanuel Bissagnene; Cleophas Chimbetete; François Dabis; Mary-Ann Davies; Christopher J Hoffmann; Patrick Oyaro; Rosalind Parkes-Ratanshi; Steven J Reynolds; Izukanji Sikazwe; Kara Wools-Kaloustian; D Marcel Zannou; Gilles Wandeler; Matthias Egger; IeDEA southern Africa, east Africa, and west Africa

doi:10.1016/S2352-3018(15)00087-9

Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis

Lancet HIV. 2015 Jul;2(7):e271-8. doi: 10.1016/S2352-3018(15)00087-9. Epub 2015 Jun 16.

Authors

Andreas D Haas¹, Olivia Keiser¹, Eric Balestre², Steve Brown³, Emmanuel Bissagnene⁴, Cleophas Chimbetete⁵, François Dabis², Mary-Ann Davies⁶, Christopher J Hoffmann⁷, Patrick Oyaro⁸, Rosalind Parkes-Ratanshi⁹, Steven J Reynolds¹⁰, Izukanji Sikazwe¹¹, Kara Wools-Kaloustian³, D Marcel Zannou¹², Gilles Wandeler¹³, Matthias Egger¹⁴; IeDEA southern Africa, east Africa, and west Africa

Collaborators

IeDEA southern Africa, east Africa, and west Africa:
Frank Tanser, Christopher Hoffmann, Benjamin Chi, Denise Naniche, Robin Wood, Desmond Tutu, Kathryn Stinson, Geoffrey Fatti, Sam Phiri, Janet Giddy, Cleophas Chimbetete, Kennedy Malisita, Brian Eley, Michael Hobbins, Kamelia Kamenova, Olatunbosun Faturiyele, Maseru Lesotho, Matthew Fox, Hans Prozesky, Karl Technau, Shobna Sawry, Matthias Egger, Julia Bohlius, Nello Blaser, Janne Estill, Olivia Keiser, Gilles Wandeler, Luisa Salazar-Vizcaya, Andreas Haas, Marie Ballif, Eliane Rohner, Natascha Wyss, Zofia Baranczuk, Kelly Goodwin, Cam Ha Dao Ostinelli, Mary-Ann Davies, Andrew Boulle, Lucy Campbell, Morna Cornell, Leigh Johnson, Nicola Maxwell, Landon Myer, Michael Schomaker, Mireille Porter, Samuel Ayaya, Lameck Diero, Edwin Sang, Elyne Rotich, Elizabeth Bukusi, Geoffrey R Somi, Rita Lyamuya, Edward Lugina, Mark Urassa, Denna Michael Mkwasa, Kapella Ngonyani, Andrew Kambugu, Philippa Easterbrook, Marion Achieng-Kariuki, Fred Nalugoda, John Ssali, Mwebesa Bosco Bwana, Winnie Muyindike, Constantin T Yiannoutsos, Beverly S Musick, Yee Yee H Kuhn, Marcel Zannou, Hubert Maga, Joseph Drabo, Adrien Bruno Sawadogo, Eugène Messou, Clarisse Amani Bosse, Henri Chenal, Albert Minga, Aristophane Koffi Tanon, Serge Olivier Koule, Christian Wejse, David Leuenberger, Jean Hebelamou, Moussa Y Maïga, Hamar Alassane Traore, Daouda Minta, Vivian Kwaghe, Festus Igbinoba, Okwara Benson, Clément Adebamowo, Moussa Seydi, Akessiwe Patassi, François Dabis, Elise Arrivé, Nathalie de Rekeneire, Antoine Jaquet, Valériane Leroy, Charlotte Lewden, Annie Sasco, Emmanuel Bissagnene, Patrick Coffie, Didier Ekouevi, Man Charurat

Affiliations

¹ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
² Centre de Recherche INSERM U897, Epidemiologie-Biostatistique, Institut de Santé Publique, Epidémiologie et Développement, Université de Bordeaux, Bordeaux, France.
³ Indiana University School of Medicine, Indianapolis, IN, USA.
⁴ Service de Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Treichville, Abidjan, Côte d'Ivoire.
⁵ Newlands Clinic, Harare, Zimbabwe.
⁶ Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.
⁷ Johns Hopkins University, Baltimore, MD, USA; Aurum Institute, Johannesburg, South Africa.
⁸ Kenya Medical Research Institute - RCTP FACES Program, Kisumu, Kenya.
⁹ Infectious Diseases Institute, Mulago Hospital Complex, Kampala, Uganda.
¹⁰ Rakai Health Sciences Program, Entebbe, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.
¹² Faculté des Sciences de la Santé de l'Université d'Abomey-Calavi, and Centre de Traitement Ambulatoire du Centre National Hospitalier Universitaire Hubert Koutoukou Maga, Cotonou, Benin.
¹³ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland.
¹⁴ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa. Electronic address: egger@ispm.unibe.ch.

Abstract

Background: HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to second-line ART in sub-Saharan Africa.

Methods: We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics.

Findings: Of 297,825 eligible patients, 10,352 (3%) switched to second-line ART during 782 ,412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine viral load monitoring, 1·21 (1·13-1·30) for targeted viral load monitoring, and 0·49 (0·43-0·56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58·0% (95% CI 56·5-59·6) switched by 2 years, and of 15,892 patients with confirmed immunological failure, 19·3% (18·5-20·0) switched by 2 years. Of 10,352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per μL (IQR 117-335) with routine viral load monitoring, but were lower with other types of monitoring (range 114-133 cells per μL).

Interpretation: Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing.

Funding: National Institute of Allergy and Infectious Diseases, Swiss National Science Foundation.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Africa South of the Sahara / epidemiology
Anti-HIV Agents / administration & dosage
Anti-HIV Agents / therapeutic use*
Antiretroviral Therapy, Highly Active / statistics & numerical data
CD4 Lymphocyte Count
Cohort Studies
Drug Monitoring*
Drug Substitution / statistics & numerical data*
Female
HIV Infections / drug therapy*
HIV Infections / epidemiology
HIV Protease Inhibitors / therapeutic use*
HIV-1 / immunology
Humans
Male
Reverse Transcriptase Inhibitors / therapeutic use*
Treatment Failure
Viral Load / drug effects

Substances

Anti-HIV Agents
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors

Abstract

Publication types

MeSH terms

Substances

Grants and funding