EDCTP Alumni Network

Fostering excellence and collaboration in the next generation of researchers

Call EDCTP Clinical Research & Development Fellowship (R&D F)
Programme EDCTP2
Start Date 2022-04-01
End Date 2023-12-29
Project Code TMA2019IF-2858
Status Active


Pfizer US

Host Organisation

Institution Country

Current Organisation

Botswana Harvard AIDS Partnership

Current Job Title

Research Associate

Students Supervised

Type Name Title University Start Date End Date


Role Committee/board Start Date End Date


Institution Degree Year
University of Liverpool, United Kingdom Msc CR
University of Zimbabwe, Zimbabwe BPharm (Hons) 1989-01-12



Jeffrey M Pernica1,2, Tonya Arscott-Mills3,4,5, Andrew P Steenhoff5, Margaret Mokomane6, Banno Moorad3, Mbabi Bapabi3, Kwana Lechiile3, Oarabile Mangwegape3, Boswa Batisani3, Norah Mawoko3, Charles Muthoga3,7, Thuvaraha Vanniyasingam2, Joycelyne Ewusie2,8, Amy Lowe9, Janice M Bonsu10, Alemayehu M Gezmu11, Marek Smieja2,12, Loeto Mazhani11, Ketil Stordal13, Lehana Thabane1,2,8,14, Matthew S Kelly15, David M Goldfarb16
BMJ Global Health

Introduction The study aim was to determine if rapid enteric diagnostics followed by the provision of targeted antibiotic therapy (‘test-and-treat’) and/or Lactobacillus reuteri DSM 17938 would improve outcomes in children hospitalised in Botswana with acute gastroenteritis.

Methods This was a multicentre, randomised, factorial, controlled, trial. Children aged 2–60 months admitted for acute non-bloody diarrhoea to four hospitals in southern Botswana were eligible. Participants were assigned to treatment groups by web-based block randomisation. Test-and-treat results were not blinded, but participants and research staff were blinded to L. reuteri/placebo assignment; this was dosed as 1×108 cfu/mL by mouth daily and continued for 60 days. The primary outcome was 60-day age-standardised height (HAZ) adjusted for baseline HAZ. All analyses were by intention to treat. The trial was registered at Clinicaltrials.gov.

Results Recruitment began on 12 June 2016 and continued until 24 October 2018. There were 66 participants randomised to the test-and-treat plus L. reuteri group, 68 randomised to the test-and-treat plus placebo group, 69 to the standard care plus L. reuterigroup and 69 to the standard care plus placebo group. There was no demonstrable impact of the test-and-treat intervention (mean increase of 0.01 SD, 95% CI −0.14 to 0.16 SD) or the L. reuteri intervention (mean decrease of 0.07 SD, 95% CI −0.22 to 0.08 SD) on adjusted HAZ at 60 days.

Conclusions In children hospitalised for acute gastroenteritis in Botswana, neither a test-and-treat algorithm targeting enteropathogens, nor a 60-day course of L. reuteri DSM 17938, were found to markedly impact linear growth or other important outcomes. We cannot exclude the possibility that test-and-treat will improve the care of children with significant enteropathogens (such as Shigella) in their stool.

H. Bussmann, C. Wester, A. Thomas, V. Novitsky, R. Okezie, T. Muzenda, T. Gaolathe, N. Ndwapi, Norah Mawoko, E. Widenfelt, S. Moyo, R. Musonda, M. Mine, J. Makhema, H. Moffat, M. Essex, V. DeGruttola, R. Marlink , 59
JAIDS Journal of Acquired Deficiency Syndrome: May 2009 – Volume 51, Issue 1, pp 37-46.

Numerous national antiretroviral (ARV) treatment initiatives offering protease inhibitor-sparing combination antiretroviral therapy (cART) have recently commenced in southern Africa, the first of which began in Botswana in January 2002. Evaluation of the efficacy and tolerability of various protease inhibitor-sparing cART regimens requires intensive study in the region, as does investigation of the development of drug resistance and the optimal means of sustaining adherence. The “Tshepo” Study is the first large-scale, randomized, clinical trial that addresses these important issues among HIV-1 subtype C-infected ARV treatment-naive adults in southern Africa. Methods:The Tshepo Study is a completed, open-labeled, randomized study that enrolled 650 ARV-naive adults between December 2002 and 2004. The study is a 3 × 2 × 2 factorial design comparing the efficacy and tolerability among factors: (1) 3 combinations of nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine (ZDV) + lamivudine (3TC), ZDV + didanosine (ddI), and stavudine (d4T) + 3TC; (2) 2 different nonnucleoside reverse transcriptase inhibitors (NNRTIs): nevirapine and efavirenz; and (3) 2 different adherence strategies: the current national “standard of care” versus an “intensified adherence strategy” incorporating a “community-based directly observed therapy.” Study patients were stratified into 2 balanced CD4+ T-cell count groups: less than 201 versus 201-350 cells per cubic millimeter with viral load greater than 55,000 copies per milliliter. Following Data Safety Monitoring Board recommendations in April 2006, ZDV/ddI-containing arms were discontinued due to inferiority in primary end point, namely, virologic failure with resistance. We report both overall data and pooled data from patients receiving ZDV/ddI- versus ZDV/3TC- and d4T/3TC-containing cART through April 1, 2006. Results:Four hundred fifty-one females (69.4%) and 199 males with a median age of 33.3 years were enrolled into the study. The median follow-up as of April 1, 2006, was 104 weeks, and loss to follow-up rate at 2 years was 4.1%. The median baseline CD4+ T-cell count was 199 cells per cubic millimeter [interquartile ratio (IQR) 136-252], and the median plasma HIV-1 RNA level was 193,500 copies per milliliter (IQR 69-250, 472-500). The proportion of participants with virologic failure and genotypic resistance mutations was 11% in those receiving ZDV/ddI-based cART versus 2% in those receiving either ZDV/3TC- or d4T/3TC-based cART (P = 0.002). The median CD4+ T-cell count increase at 1 year was 137 cells per cubic millimeter (IQR 74-223) and 199 cells per cubic millimeter (IQR 112-322) at 2 years with significantly lower gain in the ZDV/ddI arm. At 1 and 2 years, respectively, 92.0% and 88.8% of patients had an undetectable plasma HIV-1 RNA level (≤400 copies/mL). Kaplan-Meier survival estimates at 1 and 2 years were 96.6% and 95.4%. One hundred twenty patients (18.2%) had treatment-modifying toxicities, of which the most common were lipodystrophy, anemia, neutropenia, and Stevens-Johnson syndrome. There was a trend toward difference in time to treatment-modifying toxicity by pooled dual-NRTI combination and no difference in death rates. Conclusions:The preliminary study results show overall excellent efficacy and tolerability of NNRTI-based cART among HIV-1 subtype C-infected adults. ZDV/ddI-containing cART, however, is inferior to the dual NRTIs d4T/3TC or ZDV/3TC when used with an NNRTI for first-line cART.

Joseph N Jarvis 1 2 3 4 , Tshepo B Leeme 1 , Mooketsi Molefi 4 , Awilly A Chofle 5 , Gabriella Bidwell 5 , Katlego Tsholo 1 , Nametso Tlhako 1 , Norah Mawoko 1 , Raju K K Patel 1 , Mark W Tenforde 1 , Charles Muthoga 1 , Gregory P Bisson 2 , Jeremiah Kidola 5 , John Changalucha 5 , David Lawrence 3 , Shabbar Jaffar 6 , William Hope 7 , Si le F Molloy 8 , Thomas S Harrison 8 , 28
Clinical Infectious Diseases, Volume 68, Issue 3, 1 February 2019, Pages 393–401

 We performed a phase 2 noninferiority trial examining the early fungicidal activity (EFA) of 3 short-course, high-dose liposomal amphotericin B (L-AmB) regimens for cryptococcal meningitis (CM) in Tanzania and Botswana.

Methods: Human immunodeficiency virus (HIV)-infected adults with CM were randomized to (i) L-AmB 10 mg/kg on day 1 (single dose); (ii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on day 3 (2 doses); (iii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on days 3 and 7 (3 doses); or (iv) L-AmB 3 mg/kg/day for 14 days (control). All patients also received oral fluconazole 1200 mg/day for 14 days. Primary endpoint was mean rate of clearance of cerebrospinal fluid cryptococcal infection (EFA). Noninferiority was defined as an upper limit of the 2-sided 95% confidence interval (CI) of difference in EFA between intervention and control <0.2 log10 colony-forming units (CFU)/mL/day.

Results: Eighty participants were enrolled. EFA for daily L-AmB was -0.41 log10 CFU/mL/day (standard deviation, 0.11; n = 17). Difference in mean EFA from control was -0.11 (95% CI, -.29 to .07) log10 CFU/mL/day faster with single dose (n = 16); -0.05 (95% CI, -.20 to .10) log10 CFU/mL/day faster with 2 doses (n = 18); and -0.13 (95% CI, -.35 to .09) log10 CFU/mL/day faster with 3 doses (n = 18). EFA in all short-course arms was noninferior to control. Ten-week mortality was 29% (n = 23) with no statistical difference between arms. All arms were well tolerated.

Conclusions: Single-dose 10 mg/kg L-AmB was well tolerated and led to noninferior EFA compared to 14 days of 3 mg/kg/day L-AmB in HIV-associated CM. Induction based on a single 10 mg/kg L-AmB dose is being taken forward to a phase 3 clinical endpoint trial.


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