Epidemiology: Burden, Risks, and Outcomes of Treatment and Prevention

HIV/AIDS treatment programs aim to keep HIV-positive people adhering to their medication, suppressing their viral load and reducing overall morbidity and mortality. With the rapid scale-up of antiretroviral therapy (ART) in resource-constrained countries around the world, the number of HIV-positive people enrolled in treatment programs has increased dramatically. Research is needed to evaluate how effective these programs are in reducing HIV-related morbidity and mortality as well as addressing obstacles to treatment access and uptake and to long-term adherence and retention in care. CGHD researchers, local partners, and collaborators are conducting epidemiologic analyses of several cohorts, including the Themba Lethu Clinical HIV Treatment Cohort—one of the largest clinical HIV treatment databases in South Africa, which includes data on over 30,000 patients ever initiated on ART and the Right to Care Clinical Cohort which includes over 60,000 patients ever initiated on ART in South Africa. The goal of this research is to evaluate interventions aimed at improving treatment outcomes and to generate program-relevant information to improve the ART outcomes in South Africa.

  • Linkage to Care and Loss to Follow-up for HIV Treatment in South Africa: The goal of this body of research is to understand the HIV care cascade, from testing positive for HIV to linking to a treatment site to ART initiation to long-term retention in care and ART adherence. As part of this work we also seek to test interventions aimed at improving linkage to and retention in care and reducing late presentation for treatment, such as the RapIT trial of same-day treatment initiation. The results of our work on linkage to care, retention in care, and loss to follow-up have been highly influential in defining the care cascade and demonstrating that the rates of retention in HIV care programs in sub-Saharan Africa are improving over time. However, our results how that many patients are still being lost from treatment programs leading to increased mortality.
  • Use and Outcomes of Second- and Third-Line HIV Antiretroviral Therapy in South Africa: South Africa is one of the few HIV treatment programs in a resource-limited setting with access to both second- and third – line therapy as part of the national public-sector HIV treatment program. The CGHD/HE2RO team is using several clinical HIV treatment databases to evaluate the need for and effectiveness of both second-and and third- line regimens. Our results have shown patients on second-line ART are alive and in care and are achieving viral load suppression in the year after being switched. However, we have also shown that the need for second-line is increasing over time and that more recently, need for third-line has emerged in South Africa. Our results suggest that these regimens can effectively be delivered to patients who fail regimens in such settings, but come at an increased cost. These findings represent some of the first evaluations of second- and third-line ART in a resource-limited setting.

  • Monitoring South Africa’s National HIV Treatment Program Using Laboratory Data: South Africa’s national antiretroviral treatment program, the largest in the world with roughly 2.4 million people on treatment and an annual budget of 1.4 billion dollars, has made substantial impact on reducing morbidity and mortality for HIV-infected people. Monitoring and evaluation of the treatment program is critical to its sustained improvement. With this project we are attempting to use routinely collected laboratory results and link them to individuals in order to provide monitoring information on the ART treatment program at national, provincial, and local levels.
  • Evaluation of South Africa’s National Treatment Adherence Guidelines: To address high levels of loss to follow up from HIV care and treatment, South Africa intends to roll out a package of interventions as part of its National Adherence Guidelines. The package of interventions includes fast track initiation counseling for patients eligible for ART, enhanced adherence counseling for unstable patients, adherence clubs for stable patients, decentralized medication delivery for stable patients and early tracing of all patients who miss an appointment by two weeks. To evaluate the impact of this strategy, CGHD/HE2RO is working with the National Department of Health in South Africa and the World Bank to conduct a cluster randomized roll out evaluation and generate data on the costs and effectiveness of implementation.


Project Details

BOSTON UNIVERSITY INVESTIGATORS (CURRENT): Jacob Bor, Alana Brennan, Matthew Fox, Bruce Larson, William Macleod, Sydney Rosen




Clinical, Immunological and Virological Outcomes of ART

  • The International epidemiologic Databases to Evaluate AIDS (IeDEA) and ART Cohort Collaboration.   Immunodeficiency at the start of combination antiretroviral therapy in low, middle and high income countries JAIDS 2014;65:e8–e16.
  • Hoffmann CJ, Schomaker M, Fox MP, Mutevedzi P, Giddy J, Prozesky H, Wood R, Garone DB, Egger M, Boulle A, for the IeDEA Southern Africa Collaboration, CD4 count slope and mortality in HIV-infected patients on antiretroviral therapy: multi-cohort analysis from South Africa. Journal of Acquired Immune DeficiencySyndromes. 2013 May; 63(1):34-41.
  • Fox M. P., Sanne I. M., Conradie F., Zeinecker J., Orrell C., Ive P., Rassool M., Dehlinger M., van der Horst C., McIntyre J., Wood R. Initiating patients on antiretroviral therapy at CD4 cell counts above 200 cells/microl is associated with improved treatment outcomes in South Africa. AIDS 2010; 24:2041-50.

Retention on ART

  • Schomaker M, Gsponer T, Estill J, Fox MP, Boulle A. Non-ignorable loss to follow-up: correcting estimates based on inverse probability weighting and additional outcome ascertainment Statistics in Medicine 2014; 15: 129-42.

Retention in Care Before ART Initiation

  • Rosen S., Fox M. Retention in HIV Care between Testing and Treatment in Sub-Saharan Africa: A Systematic Review. PLoS Medicine. 2011 Jul; 8(7):1-16.
  • Bruce A. Larson, PhD,*† Kathryn Schnippel, MPA,‡ Buyiswa Ndibongo, BA,‡ Thembisile Xulu, MBChB, MPH,§ Alana Brennan, MPH,*‡ Lawrence Long, BBusSc, MCom,* Matthew P. Fox, MPH, DSC,*†‡ and Sydney Rosen. Rapid point-of-care CD4 testing at mobile HIV testing sites to increase linkage to care: an evaluation of a pilot program in South Africa. J Acquir Immune Defic Syndr 2012;61:e13–e17.
  • Same-day CD4 testing to improve uptake of HIV care and treatment in South Africa: point-of-care is not enough. Bruce A. Larson, Kathryn Schnippel, Alana Brennan, Lawrence Long, Thembi Xulu,  Thapelo Maotoe, Sydney Rosen, Ian Sanne, and Matthew P. Fox. AIDS Research and Treatment
 2013; Article ID 941493.

Second and Third Line ART and Drug Resistance

  • Wandeler G, Gerber F, Rohr J, Chi BH, Orrell C, Chimbetete C, Prozesky H, Boulle A, Hoffmann CJ, Gsponer T, Fox MP, Zwahlen M, Egger M, Africa IS. Tenofovir or zidovudine in second-line antiretroviral therapy after stavudine failure in southern Africa.
  • Matthew P. Fox, Gilles Van Cutsem, Janet Giddy, Mhairi Maskew, Olivia Keiser, Hans Prozesky, Robin Wood, Miguel A. Hernán, Jonathan A. C. Sterne, Matthias Egger, & Andrew Boulle. Rates and predictors of failure of first-line antiretroviral therapy and switch to second-line ART in SouthAfrica. Journal of Acquired Immune Deficiency Syndromes 2012; 60:428-437.
  • Fox M. P., Ive P., Long L., Maskew M., Sanne I. High rates of survival, immune reconstitution, and virologic suppression on second-line antiretroviral therapy in South Africa. J Acquir Immune Defic Syndr 2009; 53:500-6.