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 uses epidemiologic and economic analysis and intervention trials to help identify ways to improve the delivery of care and increase positive outcomes, fostering the long-term success of this unprecedented public health effort.
- Economics and Epidemiology of HIV/AIDS Care and Treatment: In 2008, the CGHD received an Associate Award to the Child and Family Applied Research project (CFAR) from USAID/South Africa to maintain its research program on the economics and epidemiology of HIV/AIDS care and treatment and related issues in South Africa. Under this umbrella, the CGHD is undertaking a series of studies of the costs, cost-effectiveness, and benefits of HIV/AIDS treatment; rates and predictors of treatment success and failure; and opportunities for health systems improvements in the country’s HIV and TB treatment programs. This work is done in collaboration with the CGHD’s Johannesburg-based partner, the Health Economics and Epidemiology Research Office (HE2RO). HE2RO is a division of the Wits Health Consortium of the Faculty of Health Sciences at the University of the Witwatersrand.
- Epidemiologic Analyses and HIV Treatment Outcomes in South Africa: CGHD staff, 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 demographic, clinical, and laboratory data on over 23,000 patients initiated on ART collected as part of routine HIV care. The goal is to evaluate interventions aimed at improving treatment outcomes and to generate program-relevant information to improve the ART treatment scale-up in South Africa.
- Loss to Follow-up for HIV Treatment in South Africa: The goal of this study is to evaluate interventions aimed at improving retention in care and reducing late presentation for treatment and to generate program-relevant information to improve the ART treatment scale-up in South Africa. The results of our work on loss to follow-up have been influential in demonstrating both that the rates of retention in HIV care programs in sub-Saharan Africa are improving over time, but also that many patients are still being lost from treatment programs leading to increased mortality.
- Loss to Initiation of HIV Care and Treatment in South Africa: As a starting point for designing interventions to reduce late presentation for ART care, we reviewed testing and care records at one large public-sector treatment program in Johannesburg to estimate rates of loss at two points in the testing-to-treatment continuum: 1) between testing positive for HIV and returning for CD4 count (staging) results and 2) between enrolling in the pre-ART care program and returning for the first medical appointment. Our findings on loss to initiation are informing the current debate about what interventions will have the greatest impact on linking patients to HIV care after testing positive.
- The Role of Immunosuppression in Treatment Outcomes: This study is one of the first from a resource-limited setting to show that starting patients at higher CD4 counts likely has benefits in terms of better treatment outcomes and survival. However, as patients with higher CD4 counts may also be more likely to leave care and will be required to be on treatment for longer periods of time than those initiated later, it will be critical to monitor loss to follow-up in future cohorts as changes in CD4 initiation thresholds are implemented.
- Use and Outcomes of Second-Line HIV Treatment in South Africa: To evaluate how well patients did on second-line ART, we reviewed the records of all patients who switched to standard second-line therapy after failure of first-line therapy at South Africa’s Themba Lethu Clinic. Our findings show that patients on second-line ART are alive and in care and are achieving viral load suppression in the year after being switched. These results suggest that second-line can effectively be delivered to patients who fail first-line in such settings. These findings represent one of the first evaluations of second-line ART in a resource-limited setting.
- Clinical, Immunological and Virological Outcomes of ART: Antiretroviral treatment rollout in South Africa continues to make a push towards universal access, it is important to evaluate the strategies being used to achieve these goals. Large clinical datasets of patients on antiretroviral therapy are one way to evaluate the treatment scale-up. We use data from the Themba Lethu HIV Clinic in Johannesburg, South Africa as well as data from other clinics in South Africa to evaluate treatment outcomes in relation to important aspects of the national program in South Africa over the ten years since the roll-out began.
- Retention on ART: Since large-scale access to antiretroviral therapy began in 2004 concern has been raised about the number of patients who die or are lost to follow up from care, an important indicator of treatment success. The CGHD/HE2RO team were the first to summarize rates of retention across sub-Saharan Africa and demonstrate that overall retention at two years was between 60-70%. Since then, we have done numerous evaluations of the impact of poor retention and looked at interventions to reduce attrition from HIV care with a focus on South Africa.
- Retention in Care before ART Initiation: The CGHD/HE2RO team were the first to conceptualize and summarize rates of retention along key stages in the cascade of care prior to the initiation of treatment, from HIV testing to their initial eligibility assessment (Stage 1), from their initial eligibility until they are eligible at a future visit (Stage 2), and from the date they are eligible for treatment until they actually initiate treatment. We have continued to do evaluations of retention in pre-ART care in South Africa and Zambia and looked at interventions to reduce such losses with a focus on South Africa, from rapid initiation of treatment after HIV testing to point-of-care CD4 testing.
- Monitoring Using Laboratory Data: South Africa’s national antiretroviral therapy (ART) 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.
- Second and Third Line Regimens and Drug Resistance: As HIV treatment programs mature, even if programs are highly successful, a proportion of patients will fail their first-line regimen and require switching over to second and third-line regimens. As these regimens are substantially more expensive than first-line care, it is important to evaluate the effectiveness of these regimens. In South Africa we conducted one of the first observational studies evaluating the effectiveness of these regimens in Africa under routine conditions. We are currently focused on evaluating ways to prevent the need for second- and third-line treatment.
|BOSTON UNIVERSITY INVESTIGATORS (CURRENT):||Matthew Fox, Alana Brennan, Jacob Bor, William Macleod, Sydney Rosen, Bruce Larson, Julia Rohr|
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.
- Increases in regimen durability associated with the introduction of tenofovir at a large public-sector clinic in Johannesburg, South Africa, Alana T Brennan, Mhairi Maskew, Prudence Ive, Kate Shearer, Lawrence Long, Ian Sanne and Matthew P Fox, Journal of the International AIDS Society. 2013 Nov; 16(18794).
- The Impact of Choice of NNRTI on Short-Term Treatment Outcomes among HIV-Infected Patients Prescribed Tenofovir and Lamivudine in Johannesburg, South Africa, Kate Shearer, Matthew P. Fox, Mhairi Maskew, Rebecca Berhanu, Lawrence Long, Ian Sanne, PLOS ONE. 2013 Aug; 8(8).
- A Novel Approach to Accounting for Loss to Follow-Up when Estimating the Relationship between CD4 Count at ART Initiation and Mortality, Matthew Fox, Owen McCarthy, Mead Over, PLOS ONE. 2013 Jul; 8(7).
- Anemia among HIV-Infected Patients Initiating Antiretroviral Therapy in South Africa: Improvement in Hemoglobin regardless of Degree of Immunosuppression and theInitiating ART Regimen, Simbarashe Takuva, Mhairi Maskew, Alana T. Brennan, Ian Sanne, A. Patrick MacPhail, and Mathew P. Fox, Journal of Tropical Medicine. 2013 Jul; 2013.
- Kaposi Sarcoma-Associated Herpes Virus and Response to Antiretroviral Therapy: A Prospective Study of HIV-Infected Adults, Maskew M, Shearer, K MacPhail P, Fox MP, JAIDS. 2013 Jul; 63(4):442-448.
- Treatment Response and Mortality among Patients Starting Antiretroviral Therapy with and without Kaposi Sarcoma: A Cohort Study, Maskew M, Fox MP, van Cutsem G, Chu K, MacPhail P, Boulle A, Egger M, for IeDEA Southern Africa, PLOS ONE. 2013 Jun; 8(6):1-8
- Effect of home based HIV counselling and testing intervention in rural South Africa: cluster randomised trial, Doherty T, Tabana H, Naik R, Zembe W, Jackson D, Lombard C, Swanevelder S, Fox MP, Thorson A, Ekström AM, Chopra M, BMJ. 2013 Jun; 346(f3481).
- The interplay between CD4 cell count, viral load suppression and duration of ART on mortality, Brennan A, Maskew M, Sanne I, Fox MP, Tropical Medicine and International Health. 2013 May; 18(5):619–631.
- Tuberculosis and the risk of opportunistic infections and cancers in HIV-infected patients starting ART in Southern Africa, Lukas Fenner, Stewart E. Reid, Matthew P. Fox, Daniela Garone, Maureen Wellington, Hans Prozesky, Marcel Zwahlen, Michael Schomaker, Gilles Wandeler, Nzali Kancheya, Andrew Boulle, Robin Wood, German Henostroza, and Matthias Egger, Tropical Medicine and International Health. 2013 Feb; 18(2):194-198.
- Prevalent tuberculosis and mortality among HAART initiators, Daniel Westreich, Matthew P. Fox, Annelies Van Rie and Mhairi Maskew, AIDS 2012. 2012 Jul; 26(6):770-773.
- Treatment outcomes after 7 years of public-sector HIV treatment, Matthew P. Fox, Kate Shearer, Mhairi Maskew, William Macleod, Pappie Majubae, Patrick Macphaile and Ian Sanne, AIDS 2012. 2012 Jun; 26:1823-1828.
- Cohort Profile: The Themba Lethu Clinical Cohort, Johannesburg, South Africa, Matthew P Fox, Mhairi Maskew, A Patrick MacPhail, Lawrence Long, Alana T Brennan, Daniel Westreich, William B MacLeod, Pappie Majuba & Ian M Sanne, International Journal of Epidemiology. 2012 Mar; 10(1093):1-10.
- Effectiveness and safety of 30 mg versus 40 mg stavudine regimens: a cohort study among HIV- infected adults initiating HAART in South Africa, Mhairi Maskew, Daniel Westreich, Matthew P Fox, Thapelo Maotoe and Ian M Sanne, Journal of the International AIDS Society. 2012 Mar; 15(1).
- Prevalence and predictors of kaposi sarcoma herpes virus seropositivity: a cross-sectional analysis of HIV-infected adults initiating ART in Johannesburg, South Africa, Center for Global Health & Development, Infectious Agents and Cancer. 2011 Nov; 6(22):8.
- Poorer ART Outcomes with Increasing Age in a Large South Africa Cohort, Mhairi Maskew, Alana T. Brennan, A. Patrick MacPhail, Ian M. Sanne and Matthew P. Fox, JIAPAC. 2011 Sep; 11(1):57-65.
- Southern Africa Collaboration Long-term Outcomes of Antiretroviral Treatment in Programmes With and Without Routine Viral Load Monitoring in Southern Africa, Keiser O, Chi B, Gsponer T, Boulle A, Orrell C, Phiri S, Maxwell N, Maskew M, Prozesky H, Fox MP, Westfall A, Egger M for the IeDEA, AIDS. 2011 Sep; 25(14):1761-1769.
- Relationship Between Renal Dysfunction Nephrotoxicity and Death Among HIV Adults on Tenofovir, Brennan A., Evans D., Maskew M., Naicker S., Ive P., Sanne I, Maotoe T., Fox M., AIDS 2011 Aug; 24(13):1603-1609.
- Fenner L, Forster M, Phiri S, Braitstein P, Lewden C, Schechter M, Kumarasamy N, Pascoe M, Sprinz E, El Filali KM, Bangsberg D, Sow PS, Dickinson D, Fox MP, McIntyre J, Khongphatthanayothin M, Dabis F, Brinkhof M, Boulle A, Wood R, Egger M. Tuberculosis in HIV programmes in lower-income countries: practices and risk factors. Int J Tuberc Lunc Dis. 2011 Jan; 15:1-8.
- 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.
- Loss to follow-up before and after delivery among women testing HIV positive during pregnancy in Johannesburg, South Africa, Kate Clouse, Audrey Pettifor, Kate Shearer, Mhairi Maskew, Jean Bassett, Bruce Larson, Annelies Van Rie, Ian Sanne and Matthew P. Fox, Tropical Medicine and International Health. 2013 Apr; 18(4):451-460.
- Initiating antiretroviral therapy when presenting with higher CD4 cell counts results in reduced loss to follow-up in a resource-limited setting, Kate Clouse, Audrey Pettifor, Mhairi Maskew, Jean Bassett, Annelies Van Rie, Cynthia Gay, Frieda Behets, Ian Sanne and Matthew P. Fox, AIDS 2013. 2013 Feb; 27(4):645-650.
- Patient retention from HIV diagnosis through one year on antiretroviral therapy at a primary health care clinic in Johannesburg, South Africa, Kate Clouse, Audrey E. Pettifor, Mhairi Maskew, Jean Bassett, Annelies Van Rie, Frieda Behets, Cynthia Gay, Ian Sanne, and Matthew P. Fox, JAIDS. 2013 Jan; 62(2):39-46.
- Retention in hiv care between testing and treatment in Sub-Saharan Africa: A Systematic Review, Rosen S., Fox M., PLoS Medicine. 2011 Jul; 8(7):1-16.
- Correcting mortality for loss to follow up: A nomogram applied to antiretroviral treatment programmes in sub-Saharan Africa, Matthias Egger, Ben D. Spycher, John Sidle, Ralf Weigel, Elvin H. Geng, Matthew P. Fox, Patrick MacPhail, Gilles van Cutsem, Euge`neMessou, Robin Wood, Denis Nash, Margaret Pascoe, Diana Dickinson, Jean-Franc ̧ois Etard, James A. McIntyre, Martin W. G. Brinkhof, for IeDEA East Africa, West Africa and Southern Africa, PLoS ONE Medicine. 2011 Jan; 8(1):1-11.
- The Importance of Clinic Attendance in the First Six Months on Antiretroviral Treatment (ART): Missing Medical Visits Results in Poorer ART Outcomes, Brennan A, Maskew M, Sanne I, Fox MP., Journal of International AIDS Society. 2010 Dec; 13(49).
- Patient Retention in Antiretroviral Therapy Programs Up to Three Years on Treatment in Sub-Saharan Africa, 2007-2009: Systematic Review, Fox M. P., Rosen S., Trop Med Int Health. 2010 Jul; 15 Suppl 1:1-15.
- Why are Antiretroviral Treatment Patients Lost to Follow-Up? A Qualitative Study from South Africa, Miller C. M., Ketlhapile M., Rybasack-Smith H., Rosen S., Trop Med Int Health. 2010 Jul; 15 Suppl 1:48-54.
- Cost of Using a Patient Tracer to Reduce Loss to Follow-Up and Ascertain Patient Status in a Large Antiretroviral Therapy Program in Johannesburg, South Africa, Rosen S., Ketlhapile M., Trop Med Int Health. 2010 Jul; 15 Suppl 1:98-104.
- Using Vital Registration Data to Update Mortality among Patients Lost to Follow-up from ART Programmes: Evidence from the Themba Lethu Clinic, South Africa, Fox M. P., Brennan A., Maskew M., MacPhail P., Sanne I., Trop Med Int Health. 2010 Feb; 15(4):405-13.
- Patient Retention in Antiretroviral Therapy Programs in Sub-Saharan Africa: A Systematic Review, Rosen S., Fox M. P., Gill C. J., PLoS Med. 2007 Oct; 4(10):e298.
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.
- Lost opportunities to complete CD4+ lymphocyte testing among patients who tested positive for HIV in South Africa. Larson B.A., Brennan A., McNamara L., Long L.,Rosen S., Sanne I., Fox M.P. Bull World Health Organ. 2010 Sep; 88(9):675-80.
- Early loss to follow up after enrolment in pre-ART care at a large public clinic in Johannesburg, South Africa. Larson BA, Brennan A, McNamara L, Long L, Rosen S, Sanne I, Fox MP. Trop Med Int Health 2010; 15 Suppl 1:43-7.
- 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.