Mohammed Limbada
20212022

Research activity per year

Personal profile

Research expertise

  1.  COMART Study – Community models of ART delivery

Following implementation of the HPTN 071 (PopART) trial in 2013 and changes in the WHO guidelines in 2015 to initiate ART to all PLHIV irrespective of CD4 count, the demand for HIV treatment was seen as a challenge to the capacity of health care facility infrastructure. Without a change in the current delivery model of ART care in resource-limited settings such as Zambia, lifelong ART for all PLHIV would be unsustainable. During this period there was a lot of interest in decentralizing ART care into the communities especially for those clients on stable ART, by focusing on innovative models of community ART delivery as a way of decongesting the clinics and improving patient outcome. At that time, the evidence base for community ART models were limited especially in urban settings and it was unknown which model of ART delivery was the best in terms of retention on ART and none of these models were compared to the standard of care with respect to clinical outcomes. Therefore, the ComART study was timely and innovative and designed to rigorously evaluate different community models of ART delivery and compare with the conventional model of care in an urban setting to provide critical information for the continued scale-up of universal ART. For my PhD thesis I conceptualized this non-inferiority 3-arm cluster randomized trial comparing home ART delivery and adherence clubs to that of standard of care with viral suppression as my primary endpoint. I designed the protocol with input from the HPTN 071 trial investigators and even though this was an ancillary study subject to the regulatory requirements of the larger HPTN 071 (PopART) experiment, I was responsible for the trial's leadership. With oversight and contributions from my supervisors who were the principal investigators of the main trial and HPTN 071 protocol chair and members, I designed the study (including the data collection tools), wrote the study protocol and implemented the trial in Lusaka, Zambia ad provided complete oversight. The findings showed that both differentiated models of ART delivery were found to be non-inferior to the SoC group. In addition, it was found that access to viral load measurement and retention in the community models were better compared with facility ART delivery. These findings suggest that scale up of such models of care could be beneficial in reaching viral suppression and improved retention in resource constrained settings. Full access to the thesis can be downloaded from: https://researchonline.lshtm.ac.uk/id/eprint/4664166/17/2021_ITD_PhD_Limbada_M_Thesis.pdf

 

Published Papers/Reports

1. Limbada M, Macleod D, Situmbeko V, Muhau E, Shibwela O, Chiti B, Floyd S, Schaap AJ, Hayes R, Fidler S, Ayles H; HPTN 071 (PopART) study team. Rates of viral suppression in a cohort of people with stable HIV from two community models of ART delivery versus facility-based HIV care in Lusaka, Zambia: a cluster-randomised, non-inferiority trial nested in the HPTN 071 (PopART) trial. Lancet HIV. 2022 Jan;9(1):e13-e23. doi: 10.1016/S2352-3018(21)00242-3. Epub 2021 Nov 26. PMID: 34843674; PMCID: PMC8716341

2. Limbada M, Bwalya C, Macleod D, Shibwela O, Floyd S, Nzara D, Situmbeko V, Hayes R, Fidler S, Ayles H; HPTN 071 (PopART) Study Team. Acceptability and Preferences of Two Different Community Models of ART Delivery in a High Prevalence Urban Setting in Zambia: Cluster-Randomized Trial, Nested in the HPTN 071 (PopART) Study. AIDS Behav. 2022 Feb;26(2):328-338. doi: 10.1007/s10461-021-03385-8. Epub 2021 Jul 24. PMID: 34304330; PMCID: PMC8813709.

3. Limbada M, Bwalya C, Macleod D, Floyd S, Schaap A, Situmbeko V, Hayes R, Fidler S, Ayles H; HPTN 071 (PopART) Study Team. A comparison of different community models of antiretroviral therapy delivery with the standard of care among stable HIV+ patients: rationale and design of a non-inferiority cluster randomized trial, nested in the HPTN 071 (PopART) study. Trials. 2021 Jan 12;22(1):52. doi: 10.1186/s13063-020-05010-w. PMID: 33430928; PMCID: PMC7802215.

4. Limbada M, Zijlstra G, Macleod D, Ayles H, Fidler S. A systematic review of the effectiveness of non- health facility-based care delivery of antiretroviral therapy for people living with HIV in sub-Saharan Africa measured by viral suppression, mortality and retention on ART. BMC Public Health. 2021 Jun 10;21(1):1110. doi: 10.1186/s12889-021-11053-8. PMID: 34112135; PMCID: PMC8194040.

 

Presentations I have made at international meetings and conferences

1. AIDS 2020, San Francisco, and Oakland, “Viral suppression in 'stable HIV+ patients in two community models of ART delivery: A cluster-randomized trial nested within the HPTN 071 (PopART) trial in Lusaka, Zambia.”

2. CROI 2019, Seattle. Themed Discussion: “Treat All Treat Fast”

3. IAS 2019, Mexico City, Mexico, “Retention in non-facility-based ART delivery models among stable ART patients in Lusaka, Zambia: Findings from the HPTN 071 (PopART) trial”.

4. AIDS 2018, Amsterdam, “Acceptability, and preferences of two different community models of ART delivery in a high prevalence urban setting in Zambia, nested within the HPTN 071 (PopART) trial”.

 

2. HIV Phylogenetics

PopART Phylogenetics was designed to investigate the aspects that are thought to affect the success of the PopART intervention in reducing HIV incidence. It specifically studied the role of the following factors in shaping HIV transmission in PopART communities: Transmissions from individuals with acute and early HIV infection, contributions by specific sex and age groups, transmission occurring outside the trial communities and levels of antiretroviral drug resistance. As the country PI of the study, I was involved in designing the specific country protocol under the guidance of the protocol chair and oversight of the trial which included mentoring, trainings, screening, and recruitment in the study communities within various urban towns in Zambia. This was the largest phylogenetic study of HIV ever conducted and contributed to various knowledge gaps which included the following: 1. A community-wide HIV prevention program like UTT has the potential to significantly reduce the number of new HIV infections since 30 to 40% of HIV transmissions were from persons who had been HIV positive for less than a year, 2. Men between the ages of 25 and 35 years account for a disproportionate amount of transmission of HIV. This group is less likely to be aware of their HIV status and have low treatment coverage. These findings suggest that encouraging young men to test for HIV with supported linkage to care will lead to a significant reduction in new HIV infections in the population, even though reaching them might require more effort, 3. 80% of HIV transmissions were found to occur within a given community, with the remaining 20% happening between partners from different communities. This emphasizes the importance of having continued easy access to care for people living with HIV as they move between communities and 4. Levels of drug resistance to antiretroviral therapy have increased in the past few years across all communities. The study also showed increasing levels of transmitted HIV with drug resistant viruses to first line therapy strongly supporting current practice to switch to dolutegravir regimens and emphasize the importance of regular HIV viral load monitoring with national programs for monitoring for antiretroviral drug resistance to develop robust strategies for programmatic HIV therapies.

 

Published Papers

1. Demographic characteristics of sources of HIV-1 transmission in the era of test and treat

Matthew Hall, Tanya Golubchik, David Bonsall, Lucie Abeler-Dörner, Mohammed Limbada, Barry Kosloff, Ab Schaap, Mariateresa de Cesare, George MacIntyre-Cockett, William Probert, Oliver Ratmann, Ana Bulas Cruz, Estelle Piwowar-Manning, David N Burns, Myron S Cohen, Deborah J Donnell, Susan H Eshleman, Musonda Simwinga, Richard Hayes, Sarah Fidler, Helen Ayles, Christophe Fraser.

medRxiv 2021.10.04.21263560; doi: https://doi.org/10.1101/2021.10.04.21263560

 

 

3. HPTN 071 (PopART) Study.

HPTN 071 - Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART) examined the impact of a package of HIV prevention interventions on community-level HIV incidence. The prevention interventions included universal voluntary HIV counseling and testing provided at the household level, linkage of HIV infected individuals to care and early initiation of antiretroviral therapy (ART) for all those testing HIV-positive. The study was conducted in 21 communities in the Western Cape of South Africa, and in Zambia. Findings from HPTN 071 (PopART) showed delivery of an HIV prevention strategy that includes offering HIV testing to everyone, with immediate referral to HIV care, and treatment for people living with HIV based on prevailing in-country guidelines, can substantially reduce new HIV infections. My specific role prior to the study was assist the intervention teams to develop the protocol with a focus on designing the intervention, assist in the training and implementation of the intervention packages and working in close collaboration with ministry of health and PEPFAR implementing agencies, CDC and USAID. I also had a specific role in the research component of the trial which was the population cohort by mentoring and monitoring the research teams.

 

Published Papers [as part of the HPTN 071 Study Team]

1. Bock P, Jennings K, Vermaak R, Cox H, Meintjes G, Fatti G, Kruger J, De Azevedo V, Maschilla L, Louis F, Gunst C, Grobbelaar N, Dunbar R, Limbada M, Floyd S, Grimwood A, Ayles H, Hayes R, Fidler S, Beyers N. Incidence of Tuberculosis Among HIV-Positive Individuals Initiating Antiretroviral Treatment at Higher CD4 Counts in the HPTN 071 (PopART) Trial in South Africa. J Acquir Immune Defic Syndr. 2018 Jan 1;77(1):93-101. doi: 10.1097/QAI.0000000000001560. PMID: 29016524; PMCID: PMC5720907.

2. Hayes RJ, Donnell D, Floyd S, Mandla N, Bwalya J, Sabapathy K, Yang B, Phiri M, Schaap A, Eshleman SH, Piwowar-Manning E, Kosloff B, James A, Skalland T, Wilson E, Emel L, Macleod D, Dunbar R, Simwinga M, Makola N, Bond V, Hoddinott G, Moore A, Griffith S, Deshmane Sista N, Vermund SH, El-Sadr W, Burns DN, Hargreaves JR, Hauck K, Fraser C, Shanaube K, Bock P, Beyers N, Ayles H, Fidler S; HPTN 071 (PopART) Study Team. Effect of Universal Testing and Treatment on HIV Incidence - HPTN 071 (PopART). N Engl J Med. 2019 Jul 18;381(3):207-218. doi: 10.1056/NEJMoa1814556. PMID: 31314965; PMCID: PMC6587177.

 

3. HPTN 063

HPTN 063 was a research study that sought to conduct the preliminary research required to design a behavioral intervention to reduce sexual transmission risk behaviors in HIV-infected people in care, as well as to determine whether a similar intervention structure could be used across various sexual risk groups and cultural settings. The study compared data across sites and risks group and identified commonalities and variations in participants’ sexual practices, attitudes towards sex, and sexual relationships. The main findings were: 1. Study participants described many changes in their sexual behavior because of becoming infected with HIV, including reduction in sexual activity; increased focus on condom use; and engagement in lower-risk sexual activities, 2. Most of the participants found consistent condom use to be challenging and 3. Individuals living with HIV/AIDS at all sites discussed the effects of HIV on relationships with sex partners with HIV stigma the most common thread in discussions about relationships with sex partners. My specific role in this study was that of tan Investigator of Records where I implemented the study protocol and study progress in Lusaka, Zambia.

 

Publications

1. Rogers BG, Mendez NA, Mimiaga MJ, Sherman SG, Closson EF, Tangmunkongvorakul A, Friedman RK, Limbada M, Moore AT, Srithanaviboonchai K, Mayer KH, Safren SA; HPTN 063 Study Team. "I Wasn't in My Right Mind": Qualitative Findings on the Impact of Alcohol on Condom Use in Patients Living with HIV/AIDS in Brazil, Thailand, and Zambia (HPTN 063). Int J Behav Med. 2019 Feb;26(1):17-27. doi: 10.1007/s12529-018-9739-7. PMID: 30105603; PMCID: PMC6374213.

2. Magidson JF, Li X, Mimiaga MJ, Moore AT, Srithanaviboonchai K, Friedman RK, Limbada M, Hughes JP, Cummings V, Gaydos CA, Elharrar V, Celentano D, Mayer KH, Safren SA. Antiretroviral Medication Adherence and Amplified HIV Transmission Risk Among Sexually Active HIV-Infected Individuals in Three Diverse International Settings. AIDS Behav. 2016 Apr;20(4):699-709. doi: 10.1007/s10461-015-1142-7. PMID: 26246068; PMCID: PMC4744579.

3. Safren SA, Hughes JP, Mimiaga MJ, Moore AT, Friedman RK, Srithanaviboonchai K, Limbada M, Williamson BD, Elharrar V, Cummings V, Magidson JF, Gaydos CA, Celentano DD, Mayer KH; HPTN063 Study Team. Frequency and predictors of estimated HIV transmissions and bacterial STI acquisition among HIV-positive patients in HIV care across three continents. J Int AIDS Soc. 2016 Sep 28;19(1):21096. doi: 10.7448/IAS.19.1.21096. PMID: 27687145; PMCID: PMC5043092.

Education/Academic qualification

Infectious Diseases, PhD, A comparison of different community models of Antiretroviral Therapy delivery among stable HIV+ patients in an urban setting, Zambia. A cluster-randomized non-inferiority trial., London School of Hygiene and Tropical Medicine

20-Sept-201614-Oct-2021

Award Date: 7-Dec-2021

Infectious Diseases, Msc, London School of Hygiene and Tropical Medicine

20082011

Award Date: 1-Jul-2011

Medicine , MBChB, University of Zambia

19992002

Award Date: 1-Dec-2002

Human Biology, BScHb, University of Zambia

19951998

Award Date: 1-Jan-1999

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