Senegal-Boston Research Team in 1980s, outside the laboratory of Prof. Souleymane M’Boup
Early in the AIDS epidemic, I demonstrated that the first generation of ELISA serologic screening tests for the detection of HIV infection was of lower sensitivity than the HIV confirmatory Western blot test, in early seroconversion to HIV infection. Finding the most sensitive way to detect HIV infection, especially early after exposure to HIV, was important then and now. As the newer generation of ELISA tests were able to include antigen formatting which eliminated the lower sensitivity of the early ELISA test, a new type of early HIV infection testing could occur. Knowing that the newer format of the ELISA could detect lower levels of HIV antibodies, as would be found in very early HIV infection, this allowed for simultaneous testing of a particular serum sample with both the “tuned” (newer format) and “detuned” (older format) ELISA. If the sample was only positive on the newer, more sensitive format, then this sample could be from someone in early HIV seroconversion, when one would have only low levels of HIV antibodies. Research and public health groups could then estimate incident HIV infection rates in populations using only cross-sectional surveys.
1986 Marlink, R., Allan, J., & Essex, M. Unusual Serological Profiles in AIDS. Lancet 1:1389, 1986.
1986 Marlink, R, Allan, J., McLane, M., Essex, M., Anderson, K.C., Groopman, J.E. Low Sensitivity of ELISA Testing in Early HIV Infection. New England Journal of Medicine. 315:1549, 1986.
With our group’s discovery of the existence of a second human AIDS virus, HIV-2, our collaborative Senegalese, French and U.S. team began to intensely study this new human epidemic and virus in Senegal. I documented the first clinical and hematologic descriptions of those infected in Senegal. I also established the definitive evidence in our cohort study that this new human retrovirus, HIV-2, had a dramatically reduced incidence rate of AIDS compared to HIV-1. We also demonstrated over time from seroconversion to AIDS, the distinct clinical outcomes and lower perinatal transmission rates of HIV-2 vs. HIV-1 infection in the same cohort of women in Senegal in which the initial evidence for HIV-2 was discovered.
1986 Kanki, P., Barin F., Marlink, R., et al. A New Human T-Lymphotropic Retrovirus Related to Simian T-Lymphotropic Virus Type IIIAGM (STLV-IIIAGM). Science 232:238-243, 1986.
1988 Marlink, R., Ricard, D., M’boup S., et al. Clinical, Hematologic, and Immunologic Cross-Sectional Evaluation of Individuals Exposed to Human Immunodeficiency Virus Type-2 (HIV-2). AIDS Res. Hum. Retroviruses (4)2: 137-148, 1988.
1994 Marlink, R., Kanki, P., Thior, I., et al. Reduced Rates of Disease Development with HIV-2 Compared to HIV-1. Science 265:1587-1590, 1994.
As it became clear that the vast majority of people living with HIV were not going to have access to life-saving antiretroviral therapy (ART), I helped establish scientific and clinical studies in Africa to improve access while studying how to best use ART in African settings. With a large-scale randomized controlled trial (RCT), we showed for the first time in any setting, that a specific two-drug nucleoside reversal transcriptase inhibitor (NRTI) combination, ZDV/ddI, used in Africa at that time, was distinctly inferior to other combinations. This was also the first time this combination of the first two NRTIs created were tested in an RCT against other NRTI combinations in a three-drug regimen. We also established for the first time in Africa that when the two common non-nucleoside reverse transcriptase inhibitors (NNRTIs) were used, efavirenz and nevirapine, they were both equally effective in combination with two NRTI’s, but that nevirapine had greater adverse effects.
2009 Bussmann, H., Wester, C.W., Thomas, A., Novitsky, V., Okezie, R., Muzenda, T., Gaolathe, T., Ndwapi, N., Mawoko, N., Widenfelt, E., Moyo, S., Musunda, R., Mine, M., Makhema, J., Moffat, H., Essex, E., DeGruttola, V., Marlink, R. Response to ZDV/ddI Containing Combination Antiretroviral Therapy Among HIV-1 Subtype C Infected Adults in Botswana: Two-Year Outcomes from a Randomized Clinical Trial. JAIDS, 51(1):37-46, 2009. PMCID: PMC3066172
2010 Wester C. W., Thomas A., Bussmann, H., Marlink, R. Non-nucleoside Reverse Transcriptase Inhibitor Outcomes Among Combination Antiretroviral Therapy-Treated Adults in Botswana. AIDS 24 Suppl 1, S27-S36, 2010. PMCID: PMC3087813
Several years prior to the United States government creating PEPFAR and the United States and other governments contributing funds to create the Global Fund for AIDS, Tuberculosis and Malaria, I was able to mobilize new and innovative financing to help begin the scale-up HIV/AIDS care, treatment and prevention in Africa and other resource-poor regions. (See: eci.harvard.edu, www.securethefuture.com, and www.ACHAP.org). With these early efforts to scale up an equitable response to the epidemic, I then found myself in a good position to successfully be involved in 2 of the first 4 large “Track 1.0” PEPFAR grants, given to organizations who were already working in specific developing countries needing support for HIV care and prevention. As the Botswana Country Director of Harvard’s Track 1.0 PEPFAR effort, I was able to continue to scale up national training efforts and also national monitoring and evaluations of HIV care and treatment. As Elizabeth Glaser Pediatric AIDS Foundation’s Principal Investigator for Project HEART in 5 African countries, I was also able to help the Foundation and its partner countries scale up training, improve health systems and expand HIV care, treatment and prevention to unprecedented levels. (see: Project HEART End of Project Report). National evaluations of the projects’ implementation efforts and outcomes were also now possible in Botswana and in the five Project HEART countries in Africa.
- Stringer, J.S.A., Zulu, I., Levy, J., Stringer, E.M., Mwango, A., Chi, B.H., Mtonga, V., Reid, S., Cantrell, R.A., Bulterys, M., Saag, M.S., Marlink, R., Mwinga, A., Ellerbrock, T.V., Sinkala, M. Rapid Scale-up of Antiretroviral Therapy at Primary Care Sites in Zambia: Feasibility and Early Outcomes. JAMA, 296:782-793, 2006.
- Bussmann C, Rotz, P, Ndwapi N, Baxter D, Bussmann H, Wester WC, Ncube P, Avalos A, Mine M, Mabe E, Burns PJ, Cardiello P, Makhema J, Marlink R. Strengthening Healthcare Capacity Through a Responsive, Country-Specific, Training Standard: The KITSO AIDS Training Program’s Support of Botswana’s National Antiretroviral Therapy Rollout. The Open AIDS Journal. 2:8-20, 2008.
- Schaan M, Taylor M, Puvimanasinghe J, Busang L, Keapoletswe K, Marlink R. Sexual and Reproductive Health Needs of HIV-positive Women in Botswana – a Study of Health Care Workers Views. AIDS Care. 24(9): pp 1120-5, 2012.
- Farahani, M., Vable, A., Lebelonyane, R., Seipone, K., Anderson, M., Avalos A., Chadborn, T., Tilahun, H., Roumis, D., Moeti, T., Musuka, G., Busang, L., Gaolathe, T., Malefho, K., Marlink, R. Outcomes of the Botswana National HIV/AIDS Treatment Programme from 2002 to 2010: A Longitudinal Analysis. The Lancet Global Health. 2(1), e44-e50, 2014.
- Toure S, Kouadio B, Seyler C, Traore M, Dakoury-Dogbo N, Duvignac J, Diakite N, Karcher S, Grundman C, Marlink R, N’Dri-Yoman T, Dabis F, Anglaret X. Rapid Scaling-up of Antiretroviral Therapy in 10,000 Adults in Côte d’Ivoire: Two-Year Outcomes and Determinants. AIDS. 22:873–882, 2008.
- Auld A, Moise T, Ekra K, Kouakou J, Shiraishi R, Adjorlolo-Johnson G, Marlink R, Ellerbrock T. Tuberculosis in Human Immunodeficiency Virus-Infected Children Starting Antiretroviral Therapy – Cote d’Ivoire. The International Journal of Tuberculosis and Lung Disease. 18(4), 381-387, 2014.
- Auld A, Tuho M, Shiraishi R, Ekra K, Mohamed F, Diaby L, Kouakou J, Ettiegne-Traore V, Sabatier J, Likos A, Essombo J, Adjorlolo-Johnson G, Marlink R, Ellerbrock T. Temporal Trends in Treatment Outcomes for HIV-1 and HIV-2-Infected Adults Enrolled in Côte d’Ivoire’s National Antiretroviral Therapy Program. PloS one. 9(5): e98183, 2014.
- Auld A, Sabatier J, Shiraishi R, Rivadeneira E, Ekra K, Likos A, Kouakou J, KIaby L, Mohmmed F, Tanoh A, Essombo J, Virginie ET, Moise T, Marlink R, Adjorlolo-Johnson G, Ellerbrock T. Temporal Trends in Mortality and Loss to Follow-up Among Children Enrolled in Côte d’Ivoire’s National Antiretroviral Therapy Program. The Pediatric Infectious Disease Journal. 33(11): 1134-1140, 2014.
With the multi-country Project HEART, unique evaluations across countries could now also be accomplished.
- Adjorlolo-Johnson, G., Wahl, A., Ramachandran, S., Strasser, S., Kouakou, J., Tindyebwa, D., Alons, C., Neluheni, T., Lee, S., Marlink, R. Scaling up Pediatric HIV Care and Treatment in Africa: Clinical Site Characteristics Associated with Favorable Service Utilization. J Acquir Immune Defic Syndr. Jan 1;62(1):e7-e13, 2013.
- Liu K, Farahani M, Mashamba T, Mawela M, Joseph J, Van Schaik N, Honey E, Gill M, Jassat W, Stringer E, Chintu N, Marlink R. Pregnancy Outcomes and Birth Defects From an Antiretroviral Drug Safety Study of Women in South Africa and Zambia. AIDS. 24(15), 2014.
- Auld A, Agolory G, Shiraishi W, Wabwire-Mangen F, Kwesigabo G, Mulenga M, Hachizovu S, Asadu E, Tuho Z, Ettiegne-Traore V, Mbofana, F, Okello V, Azih C, Denison A, Tsui S, Koole O, Kamiru H, Nuwagaba-Biribonwoha H, Alfredo C, Jobarteh K, Odafe S, Onotu D, Ekra A, Kouakou S, Ehrenkranz P, Bicego G, Torpey K, Mukadi D, Praag E, Menten J, Mastro T, Hamil-ton D, Swaminathan M, Dokubo K, Baughman L, Spira T, Colebunders R, Bangsberg D, Marlink R, Zee A, Kaplan J, Ellerbrock V. Antiretroviral Therapy Enrollment Characteristics and Outcomes Among HIV-Infected Adolescents and Young Adults Compared with Older Adults – Seven African Countries, 2004-2013. MMWR Morb Mortal Wkly Rep. 63(47): 1097-1103, 2014.
My colleague, Dr. Wafaie Fawzi, had found in Tanzania in a nutritional study of post-partum women living with HIV, but not on ART, that the progression to AIDS seemed to be slowed with a specific multivitamin combination that excluded the use of Vitamin A in the preparation. This finding was both dramatic and unexpected. We felt that the finding needed confirmation in both women and men, and in the era of ART now becoming available in Africa. With colleagues from Florida International University, we replicated the study in Botswana via a RCT giving the same multivitamin combination, and also testing the potential effect of the micronutrient, selenium, with placebos in a 2 X 2 factorial design. We showed that after just 2 years, the likelihood of progressing to either AIDS or death was reduced by half in a cohort of people living with HIV, not yet eligible for ART. Follow up studies are urgently warranted.
- Baum M, Campa A, Sales S, Tsalaile L, Burns P, Lai S, Li Y, van Widenfelt E, Page JB, Bussmann H, Fawzi W, Sikhulele M, Makhema J, Thior I, Essex M, Marlink R. Randomized Clinical Trial of Micronutrient Supplementation to Delay Disease Progression in HIV-positive Adults Prior to ART in Botswana. JAMA. 310(20): pp 2154-2163, 2013.
Complete List of Published Work in my Pubmed Bibliography: http://www.ncbi.nlm.nih.gov/pubmed/?term=marlink