Khatija Ahmed
@setshabaresearchcentre.org.za
Chief Executive Officer
Setshaba Research Centre
RESEARCH INTERESTS
SRC prides itself on conducting high-quality clinical trials with excellent recruitment and retention rates and high-quality data.
The site’s core focus upon inception was conducting HIV prevention studies. Since then, the site has demonstrated the ability to expand its portfolio to include HIV and
Scopus Publications
Scopus Publications
Samantha Fry, Kulkanya Chokephaibulkit, Sridevi Pallem, Ouzama Henry, Yongjia Pu, Agnes Akawung, Joon Hyung Kim, Emad Yanni, Antonella Nadia Tullio, Linda Aurpibul,et al.
Oxford University Press (OUP)
Abstract Background Incidence data of respiratory syncytial virus–associated lower respiratory tract illness (RSV-LRTI) are sparse in low- and middle-income countries (LMICs). We estimated RSV-LRTI incidence rates (IRs) in infants in LMICs using World Health Organization case definitions. Methods This prospective cohort study, conducted in 10 LMICs from May 2019 to October 2021 (largely overlapping with the coronavirus disease 2019 [COVID-19] pandemic), followed infants born to women with low-risk pregnancies for 1 year from birth using active and passive surveillance to detect potential LRTIs, and quantitative reverse-transcription polymerase chain reaction on nasal swabs to detect RSV. Results Among 2094 infants, 32 (1.5%) experienced an RSV-LRTI (8 during their first 6 months of life, 24 thereafter). Seventeen (0.8%) infants had severe RSV-LRTI and 168 (8.0%) had all-cause LRTI. IRs (95% confidence intervals [CIs]) of first RSV-LRTI episode were 1.0 (.3–2.3), 0.8 (.3–1.5), and 1.6 (1.1–2.2) per 100 person-years for infants aged 0–2, 0–5, and 0–11 months, respectively. IRs (95% CIs) of the first all-cause LRTI episode were 10.7 (8.1–14.0), 11.7 (9.6–14.0), and 8.7 (7.5–10.2) per 100 person-years, respectively. IRs varied by country (RSV-LRTI: 0.0–8.3, all-cause LRTI: 0.0–49.6 per 100 person-years for 0- to 11-month-olds). Conclusions RSV-LRTI IRs in infants in this study were relatively low, likely due to reduced viral circulation caused by COVID-19–related nonpharmaceutical interventions. Clinical Trials Registration NCT03614676.
Courtney Peasant Bonner, Alexandra M. Minnis, Jacqueline W. Ndirangu, Felicia A. Browne, Ilene Speizer, Laura Nyblade, Khatija Ahmed, and Wendee M. Wechsberg
Springer Science and Business Media LLC
Erica N. Browne, Kgahlisho Manenzhe, Wanzirai Makoni, Sikhanyisiwe Nkomo, Imelda Mahaka, Khatija Ahmed, Mary Kate Shapley-Quinn, Tozoe Marton, Ellen Luecke, Leah Johnson,et al.
Springer Science and Business Media LLC
Abstract Background Input from end-users during preclinical phases can support market fit for new HIV prevention technologies. With several long-acting pre-exposure prophylaxis (PrEP) implants in development, we aimed to understand young women’s preferences for PrEP implants to inform optimal design. Methods We developed a discrete choice experiment and surveyed 800 young women in Harare, Zimbabwe and Tshwane, South Africa between September–November 2020. Women aged 18–30 years who were nulliparous, postpartum, or exchanged sex for money, goods or shelter in prior year were eligible; quotas were set for each subgroup. The DCE asked participants to choose between two hypothetical implants for HIV prevention in a series of nine questions. Implants were described by: size, number of rods and insertion sites, duration (6-months, 1-year, 2-years), flexibility, and biodegradability. Random-parameters logit models estimated preference weights. Results Median age was 24 years (interquartile range 21–27). By design, 36% had used contraceptive implants. Duration of protection was most important feature, with strong preference for a 2-year over 6-month implant. In Zimbabwe, the number of rods/insertion sites was second most important and half as important as duration. Nonetheless, to achieve an implant lasting 2-years, 74% were estimated to accept two rods, one in each arm. In South Africa, preference was for longer, flexible implants that required removal, although each of these attributes were one-third as important as duration. On average, biodegradability and size did not influence Zimbabwean women’s choices. Contraceptive implant experience and parity did not influence relative importance of attributes. Conclusions While duration of protection was a prominent attribute shaping women’s choices for PrEP implants, other characteristics related to discreetness were relevant. Optimizing for longest dosing while also ensuring minimal detection of implant placement seemed most attractive to potential users.
Rushil Harryparsad, Bahiah Meyer, Ongeziwe Taku, Myrna Serrano, Pai Lien Chen, Xiaoming Gao, Anna-Lise Williamson, Celia Mehou-Loko, Florence Lefebvre d’Hellencourt, Jennifer Smit,et al.
Public Library of Science (PLoS)
Background South Africa is among the countries with the highest prevalence of sexually transmitted infections (STIs), including Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). In 2017, there were an estimated 6 million new CT, 4.5 million NG and 71 000 Treponema pallidum infections among South African men and women of reproductive age. Methods We evaluated STI prevalence and incidence and associated risk factors in 162 women aged 18–33 years old, residing in eThekwini and Tshwane, South Africa who were part of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. Women were randomised to use depot medroxyprogesterone acetate (n = 53), copper intrauterine device (n = 51), or levonorgestrel (n = 58) implant. Lateral vaginal wall swab samples were collected prior to contraceptive initiation and at months one and three following contraceptive initiation for STI testing. Results There were no significant differences in STI incidence and prevalence across contraceptive groups. At baseline, 40% had active STIs (CT, NG, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) or herpes simplex virus-2 shedding across all age groups– 18–21 years (46%), 22–25 years (42%) and 26–33 years (29%). The incidence of STIs during follow-up was exceptionally high (107.9/100 women-years [wy]), with younger women (18–21 years) more likely to acquire CT (75.9/100 wy) compared to 26–33 year olds (17.4/100 wy; p = 0.049). TV incidence was higher in the 26–33 year old group (82.7/100 wy) compared to the 18–21 year olds (8.4/100 wy; p = 0.01). Conclusions Although the study participants received extensive counselling on the importance of condom use, this study highlights the high prevalence and incidence of STIs in South African women, especially amongst young women, emphasising the need for better STI screening and management strategies.
Olivier Paccoud, Liliwe Shuping, Rudzani Mashau, Greg Greene, Vanessa Quan, Susan Meiring, Nelesh P. Govender, Shareef Abrahams, Khatija Ahmed, Theunis Avenant,et al.
Elsevier BV
Khatija Ahmed, Mookho Malahleha, Thulisile E. Mbatsane, Dineo Thindisa, Veronique C. Bailey, Ishen Seocharan, and Athmanundh Dilraj
Academy of Science of South Africa
In clinical trials, a vital protocol requirement for participants is adherence to scheduled visits. A substantial number of missed visits and the resultant missing data could affect generalisability of the findings and undermine the scientific conclusions. We aimed to investigate the extent of and reasons for missed visits in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial in order to optimise recruitment and retention practices. Despite being a multi-country study, we investigated missed visits only at Setshaba Research Centre in Soshanguve, Tshwane, South Africa. Of 810 participants enrolled at Setshaba Research Centre, 94 (11.6%) participants missed visits and 231 missed visits were recorded. Of the 94 participants who missed visits, 53 (56.4%) missed at least two visits; 37 (39.4%) missed three or more visits, and of these, 32 (86.5%) missed at least two visits for the same reason. Overall, the main reasons for missed visits were: participant had to work (60; 26.0%), unable to contact participant (60; 26.0%), participant relocated (32; 13.9%), and participant travelled out of area (23; 10%). The large proportion of participants who missed two or more visits indicates that participants who miss a single visit are likely to miss even more, often for the same reason. Site staff need to be vigilant to detect any trends in missed visits early and innovative in developing personalised strategies to minimise missed visits and retain participants until completion of their scheduled visits.
Paulina Kaplonek, Deniz Cizmeci, Gaurav Kwatra, Alane Izu, Jessica Shih-Lu Lee, Harry L. Bertera, Stephanie Fischinger, Colin Mann, Fatima Amanat, Wenjun Wang,et al.
Springer Science and Business Media LLC
AbstractDespite the success of COVID-19 vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged that can cause breakthrough infections. Although protection against severe disease has been largely preserved, the immunological mediators of protection in humans remain undefined. We performed a substudy on the ChAdOx1 nCoV-19 (AZD1222) vaccinees enrolled in a South African clinical trial. At peak immunogenicity, before infection, no differences were observed in immunoglobulin (Ig)G1-binding antibody titers; however, the vaccine induced different Fc-receptor-binding antibodies across groups. Vaccinees who resisted COVID-19 exclusively mounted FcγR3B-binding antibodies. In contrast, enhanced IgA and IgG3, linked to enriched FcγR2B binding, was observed in individuals who experienced breakthrough. Antibodies unable to bind to FcγR3B led to immune complex clearance and resulted in inflammatory cascades. Differential antibody binding to FcγR3B was linked to Fc-glycosylation differences in SARS-CoV-2-specific antibodies. These data potentially point to specific FcγR3B-mediated antibody functional profiles as critical markers of immunity against COVID-19.
Anthonet L. Koen, Alane Izu, Vicky Baillie, Gaurav Kwatra, Clare L. Cutland, Lee Fairlie, Sherman D. Padayachee, Keertan Dheda, Shaun L. Barnabas, Qasim Ebrahim Bhorat,et al.
Elsevier BV
Sikhanyisiwe Nkomo, Wanzirai Makoni, Mary Kate Shapley-Quinn, Ellen Luecke, Enough Mbatsane, Kgahlisho Manenzhe, Khatija Ahmed, Leah M. Johnson, Imelda Mahaka, and Ariane van der Straten
Public Library of Science (PLoS)
Background Given the high rates of both HIV and unintended pregnancies in sub-Saharan Africa, the SCHIELD program aims to develop a multipurpose technology implant for HIV and pregnancy prevention. An end-user evaluation was undertaken with young women and health care providers to assess preferences for modifiable implant attributes to improve future adoption and rollout. Methods Focus group discussions were conducted with potential women end users, and health care providers experienced in implant insertion or removal participated in in-depth interviews. All participants were recruited from Harare, Zimbabwe, or Soshanguve, South Africa. The purposively stratified sampled women were either implant experienced or implant naïve and were categorized into three groups: nulliparous, postpartum, or engaged in transactional sex. Topics covered included duration (six months to three years), biodegradability, removability, and independent rod retrievability (per indication). Data were analyzed using Dedoose software and summarized into emerging themes. Results Participants identified three key areas that could facilitate rollout, uptake, and adherence of an implant for HIV and pregnancy prevention. First, discreetness was the most salient topic and was associated with implant characteristics such as anatomical location, flexibility, and biodegradability. Second, the ability to independently retrieve the HIV or pregnancy prevention component was preferred, as life circumstances may change and was favored by all participants, except for young women in Soshanguve. Third, there is a need for proper counseling, sensitization, provider training, and health campaigns to facilitate rollout of a 2-in-1 implant. Conclusions A 2-in-1 implant was seen as highly desirable by most young women and health care providers. Participants discussed potential concerns and barriers to uptake of a biodegradable implant with dual HIV prevention and contraceptive properties, identifying key implant attributes that product developers can modify while still in preclinical stages.
Shabir A Madhi, Gaurav Kwatra, Simone I Richardson, Anthonet L Koen, Vicky Baillie, Clare L Cutland, Lee Fairlie, Sherman D Padayachee, Keertan Dheda, Shaun L Barnabas,et al.
Elsevier BV
Muneerah Smith, Gaurav Kwatra, Alane Izu, Andrew Nel, Clare Cutland, Khatja Ahmed, Vicky Baillie, Shaun Barnabas, Qasim Bhorat, Carmen Briner,et al.
MDPI AG
Vaccines against SARS-CoV-2 have been pivotal in overcoming the COVID-19 pandemic yet understanding the subsequent outcomes and immunological effects remain crucial, especially for at-risk groups e.g., people living with human immunodeficiency virus (HIV) (PLWH). In this study we report the longitudinal IgA and IgG antibody titers, as well as antibody-mediated angiotensin converting enzyme 2 (ACE2) binding blockade, against the SARS-CoV-2 spike (S) proteins after 1 and 2 doses of the ChAdOx1 nCoV-19 vaccine in a population of Black PLWH. Here, we report that PLWH (N = 103) did not produce an anti-S IgA response after infection or vaccination, however, anti-S IgG was detected in response to vaccination and infection, with the highest level detected for infected vaccinated participants. The anti-IgG and ACE2 blockade assays revealed that both vaccination and infection resulted in IgG production, however, only vaccination resulted in a moderate increase in ACE2 binding blockade to the ancestral S protein. Vaccination with a previous infection results in the greatest anti-S IgG and ACE2 blockade for the ancestral S protein. In conclusion, PLWH produce an anti-S IgG response to the ChAdOx1 nCoV-19 vaccine and/or infection, and ChAdOx1 nCoV-19 vaccination with a previous infection produced more neutralizing antibodies than vaccination alone.
Irina Yacobson, Valentine Wanga, Khatija Ahmed, Tsungai Chipato, Peter Gichangi, James Kiarie, Cheryl Louw, Susan Morrison, Margaret Moss, Nelly R. Mugo,et al.
Elsevier BV
M Malahleha, A Dilraj, J Jean, NS Morar, JJ Dietrich, M Ross, E Mbatsane, MC Keefer, and K Ahmed
South African Medical Association NPC
Background. The high HIV prevalence and incidence in South Africa makes it suitable for recruitment of participants for large-scale HIV preventive vaccine trials. However, fear of vaccine-induced seropositivity (VISP) may be a barrier for community acceptability of the trial, for volunteers to participate in HIV preventive vaccine trials and for uptake of an efficacious vaccine. Prior to 2015, when the first phase 1 safety HIV vaccine trial was undertaken at Setshaba Research Centre, Soshanguve, the local community stakeholders and healthcare workers were naive about HIV vaccine research and HIV preventive vaccines.Objective. To explore knowledge and perceptions regarding VISP among community stakeholders and healthcare workers in peri-urbanb Soshanguve, Tshwane.Methods. Using a quantitative-qualitative mixed-methods study design, surveys (n=50) and in-depth interviews (n=18) were conducted during July - August 2015. Participants included community stakeholders, community advisory board members and healthcare workers, who were >18 years old and had attended community educational workshops during September 2014 - May 2015. Audio recordings of interviews were transcribed verbatim and coded using content thematic analysis. Data were further analysed by sex, age and educational level.Results. Of a maximum score of 2 on knowledge on VISP, the 50 survey participants (mean age 33.78 years; 45 females) obtained anaverage of 0.88 (44%). Of 17 in-depth interviewees (one interview could not be transcribed; mean age 30.9 years; 12 females), 8 (47%)displayed some knowledge about VISP, of whom only 5 defined VISP correctly. Women were more knowledgeable about VISP than men; 5 of 12 women (42%) came close to defining VISP correctly, while none of the 5 men did so. The main fear of trial participation expressed by most participants (n=6) was testing HIV-positive as a result of the vaccine. While some participants believed that the community’s perceptions of VISP would negatively affect HIV vaccine trial support and recruitment efforts, others noted that if trial participants understand the concept of VISP and are part of support groups, then they would have the information to combat negative attitudes within their community.Conclusion. Most participants had an inaccurate and incomplete understanding of VISP. Many feared testing HIV-positive at clinics;therefore, education on improving a basic understanding of how vaccines work and why VISP occurs is essential. In addition, assessingparticipant understanding of HIV testing, transmission and VISP is critical for recruitment of participants into HIV vaccine trials and may improve acceptability of an HIV preventive vaccine.
Laura Nyblade, Jacqueline W. Ndirangu, Ilene S. Speizer, Felicia A. Browne, Courtney Peasant Bonner, Alexandra Minnis, Tracy L. Kline, Khatija Ahmed, Brittni N. Howard, Erin N. Cox,et al.
Springer Science and Business Media LLC
Abstract Background Globally, an urgent need exists to expand access to HIV prevention among adolescent girls and young women (AGYW), but the need is particularly acute in sub-Saharan Africa. Oral pre-exposure prophylaxis (PrEP) offers an effective HIV prevention method. In many countries, however, accessing PrEP necessitates that AGYW visit their local health clinic, where they may face access challenges. Some countries have implemented youth-friendly services to reduce certain challenges in local health clinics, but barriers to access persist, including clinic stigma. However, evidence of clinic stigma toward AGYW, particularly with respect to PrEP service delivery, is still limited. This mixed methods study explores stigma toward AGYW seeking clinic services, in particular PrEP, from the perspective of both clinic staff (clinical and nonclinical) and AGYW who seek services at clinic sites in Tshwane province, South Africa. Methods Six focus group discussions were conducted with AGYW (43 total participants) and four with clinic staff (42 total participants) and triangulated with survey data with AGYW (n = 449) and clinic staff (n = 130). Thematic analysis was applied to the qualitative data and descriptive statistics were conducted with the survey data. Results Four common themes emerged across the qualitative and quantitative data and with both AGYW and clinic staff, although with varying degrees of resonance between these two groups. These themes included (1) clinic manifestations of stigma toward AGYW, (2) concerns about providing PrEP services for AGYW, (3) healthcare providers’ identity as mothers, and (4) privacy and breaches of confidentiality. An additional theme identified mainly in the AGYW data pertained to stigma and access to healthcare. Conclusion Evidence is needed to inform strategies for addressing clinic stigma toward AGYW, with the goal of removing barriers to PrEP services for this group. While awareness has increased and progress has been achieved around the provision of comprehensive, youth-friendly sexual and reproductive health services, these programs need to be adapted for the specific concerns of young people seeking PrEP services. Our findings point to the four key areas noted above where programs seeking to address stigma toward AGYW in clinics can tailor their programming.
Ivana Beesham, Urvi M. Parikh, John W. Mellors, Dvora L. Joseph Davey, Renee Heffron, Thesla Palanee-Phillips, Shannon L. Bosman, Mags Beksinska, Jennifer Smit, Khatija Ahmed,et al.
Ovid Technologies (Wolters Kluwer Health)
Background: Pretreatment HIV drug resistance (PDR) undermines individual treatment success and threatens the achievement of UNAIDS 95-95-95 targets. In many African countries, limited data are available on PDR as detection of recent HIV infection is uncommon and access to resistance testing is limited. We describe the prevalence of PDR among South African women with recent HIV infection from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. Methods: HIV-uninfected, sexually active women, aged 18–35 years, and seeking contraception were enrolled in the ECHO Trial at sites in South Africa, from 2015 to 2018. HIV testing was done at trial entry and repeated quarterly. We tested stored plasma samples collected at HIV diagnosis from women who seroconverted during follow-up and had a viral load >1000 copies/mL for antiretroviral resistant mutations using a validated laboratory-developed population genotyping assay, which sequences the full protease and reverse transcriptase regions. Mutation profiles were determined using the Stanford Drug Resistance Database. Results: We sequenced 275 samples. The median age was 23 years, and majority (98.9%, n = 272) were infected with HIV-1 subtype C. The prevalence of surveillance drug resistance mutations (SDRMs) was 13.5% (n = 37). Nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations were found in 12.4% of women (n = 34). Few women had NRTI (1.8%, n = 5) and protease inhibitor (1.1%, n = 3) mutations. Five women had multiple NRTI and NNRTI SDRMs. Conclusions: The high levels of PDR, particularly to NNRTIs, strongly support the recent change to the South African national HIV treatment guidelines to transition to a first-line drug regimen that excludes NNRTIs.
Ivana Beesham, Leila E. Mansoor, Dvora L. Joseph Davey, Thesla Palanee-Phillips, Jenni Smit, Khatija Ahmed, Pearl Selepe, Cheryl Louw, Mandisa Singata-Madliki, Philip Kotze,et al.
Ovid Technologies (Wolters Kluwer Health)
Background: HIV endpoint–driven clinical trials provide oral pre-exposure prophylaxis (PrEP) as HIV prevention standard of care. We evaluated quantifiable plasma tenofovir among South African women who used oral PrEP during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. Methods: ECHO, a randomized trial conducted in 4 African countries between 2015 and 2018, assessed HIV incidence among HIV-uninfected women, aged 16–35 years, randomized to 1 of 3 contraceptives. Oral PrEP was offered onsite as part of the HIV prevention package at the South African trial sites. We measured tenofovir in plasma samples collected at the final trial visit among women reporting ongoing PrEP use. We used bivariate and multivariate logistical regression to assess demographic and sexual risk factors associated with plasma tenofovir quantification. Results: Of 260 women included, 52% were ≤24 years and 22% had Chlamydia trachomatis at enrollment. At PrEP initiation, 68% reported inconsistent/nonuse of condoms. The median duration of PrEP use was 90 days (IQR: 83–104). Tenofovir was quantified in 36% (n = 94) of samples. Women >24 years had twice the odds of having tenofovir quantified vs younger women (OR = 2.12; 95% confidence interval = 1.27 to 3.56). Women who reported inconsistent/nonuse of condoms had lower odds of tenofovir quantification (age-adjusted OR = 0.47; 95% confidence interval = 0.26 to 0.83). Conclusions: Over a third of women initiating PrEP and reporting ongoing use at the final trial visit had evidence of recent drug exposure. Clinical trials may serve as an entry point for PrEP initiation among women at substantial risk for HIV infection with referral to local facilities for ongoing access at trial end. Clinical trial number: NCT02550067.
Nina Radzey, Rushil Harryparsad, Bahiah Meyer, Pai Lien Chen, Xiaoming Gao, Charles Morrison, Ongeziwe Taku, Anna‐Lise Williamson, Celia Mehou‐Loko, Florence Lefebvre d'Hellencourt,et al.
Wiley
PROBLEM
Data on the effects of contraceptives on female genital tract (FGT) immune mediators are inconsistent, possibly in part due to pre-existing conditions that influence immune mediator changes in response to contraceptive initiation.
METHODS
This study included 161 South African women randomised to injectable depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD), or levonorgestrel (LNG) implant in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. We measured thirteen cytokines and antimicrobial peptides previously associated with HIV acquisition in vaginal swabs using Luminex and ELISA, before, and at 1 and 3 months after contraceptive initiation. Women were grouped according to an overall baseline inflammatory profile. We evaluated modification of the relationships between contraceptives and immune mediators by baseline inflammation, demographic, and clinical factors.
RESULTS
Overall, LNG implant and copper IUD initiation were associated with increases in inflammatory cytokines, while no changes were observed following DMPA-IM initiation. However, when stratifying by baseline inflammatory profile, women with low baseline inflammation in all groups experienced significant increases in inflammatory cytokines, while those with a high baseline inflammatory profile experienced no change or decreases in inflammatory cytokines.
CONCLUSION
We conclude that pre-contraceptive initiation immune profile modifies the effect of contraceptives on the FGT innate immune response. This article is protected by copyright. All rights reserved.
Nigel Garrett, Asa Tapley, Jessica Andriesen, Ishen Seocharan, Leigh H Fisher, Lisa Bunts, Nicole Espy, Carole L Wallis, April Kaur Randhawa, Maurine D Miner,et al.
Oxford University Press (OUP)
Abstract We report a 23% asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) Omicron carriage rate in participants being enrolled into a clinical trial in South Africa, 15-fold higher than in trials before Omicron. We also found lower CD4 + T-cell counts in persons with human immunodeficiency virus (HIV) strongly correlated with increased odds of being SARS-CoV-2 polymerase chain reaction (PCR) positive.
Simbarashe Takuva, Azwidhwi Takalani, Ishen Seocharan, Nonhlanhla Yende-Zuma, Tarylee Reddy, Imke Engelbrecht, Mark Faesen, Kentse Khuto, Carmen Whyte, Veronique Bailey,et al.
Public Library of Science (PLoS)
Background Real-world evaluation of the safety profile of vaccines after licensure is crucial to accurately characterise safety beyond clinical trials, support continued use, and thereby improve public confidence. The Sisonke study aimed to assess the safety and effectiveness of the Janssen Ad26.COV2.S vaccine among healthcare workers (HCWs) in South Africa. Here, we present the safety data. Methods and findings In this open-label phase 3b implementation study among all eligible HCWs in South Africa registered in the national Electronic Vaccination Data System (EVDS), we monitored adverse events (AEs) at vaccination sites through self-reporting triggered by text messages after vaccination, healthcare provider reports, and active case finding. The frequency and incidence rate of non-serious and serious AEs were evaluated from the day of first vaccination (17 February 2021) until 28 days after the final vaccination in the study (15 June 2021). COVID-19 breakthrough infections, hospitalisations, and deaths were ascertained via linkage of the electronic vaccination register with existing national databases. Among 477,234 participants, 10,279 AEs were reported, of which 138 (1.3%) were serious AEs (SAEs) or AEs of special interest. Women reported more AEs than men (2.3% versus 1.6%). AE reports decreased with increasing age (3.2% for age 18–30 years, 2.1% for age 31–45 years, 1.8% for age 46–55 years, and 1.5% for age > 55 years). Participants with previous COVID-19 infection reported slightly more AEs (2.6% versus 2.1%). The most common reactogenicity events were headache (n = 4,923) and body aches (n = 4,483), followed by injection site pain (n = 2,767) and fever (n = 2,731), and most occurred within 48 hours of vaccination. Two cases of thrombosis with thrombocytopenia syndrome and 4 cases of Guillain-Barré Syndrome were reported post-vaccination. Most SAEs and AEs of special interest (n = 138) occurred at lower than the expected population rates. Vascular (n = 37; 39.1/100,000 person-years) and nervous system disorders (n = 31; 31.7/100,000 person-years), immune system disorders (n = 24; 24.3/100,000 person-years), and infections and infestations (n = 19; 20.1/100,000 person-years) were the most common reported SAE categories. A limitation of the study was the single-arm design, with limited routinely collected morbidity comparator data in the study setting. Conclusions We observed similar patterns of AEs as in phase 3 trials. AEs were mostly expected reactogenicity signs and symptoms. Furthermore, most SAEs occurred below expected rates. The single-dose Ad26.COV2.S vaccine demonstrated an acceptable safety profile, supporting the continued use of this vaccine in this setting. Trial registration ClinicalTrials.gov NCT04838795; Pan African Clinical Trials Registry PACTR202102855526180.
T. Palanee-Phillips, H. Rees, Kate B. Heller, K. Ahmed, J. Batting, I. Beesham, R. Heffron, J. Justman, Heeran Makkan, T. Mastro,et al.
Introduction South Africa has the highest national burden of HIV globally. Understanding drivers of HIV acquisition in recently completed, prospective studies in which HIV was an endpoint may help inform the strategy and investments in national HIV prevention efforts and guide the design of future HIV prevention trials. We assessed HIV incidence and correlates of incidence among women enrolled in ECHO (Evidence for Contraceptive Options and HIV Outcomes), a large, open-label randomized clinical trial that compared three highly effective. reversible methods of contraception and rates of HIV acquisition. Methods During December 2015 to October 2018, ECHO followed sexually active, HIV-seronegative women, aged 16–35 years, seeking contraceptive services and willing to be randomized to one of three contraceptive methods (intramuscular depot medroxyprogesterone acetate, copper intrauterine device, or levonorgestrel implant) for 12–18 months at nine sites in South Africa. HIV incidence based on prospectively observed HIV seroconversion events. Cox proportional hazards regression models were used to define baseline cofactors related to incident HIV infection. Results 5768 women were enrolled and contributed 7647 woman-years of follow-up. The median age was 23 years and 62.5% were ≤24 years. A total of 345 incident HIV infections occurred, an incidence of 4.51 per 100 woman-years (95%CI 4.05–5.01). Incidence was >3 per 100 woman-years at all sites. Age ≤24 years, baseline infection with sexually transmitted infections, BMI≤30, and having new or multiple partners in the three months prior to enrollment were associated with incident HIV. Conclusions HIV incidence was high among South African women seeking contraceptive services. Integration of diagnostic management of sexually transmitted infections alongside delivery of HIV prevention options in health facilities providing contraception services are needed to mitigate ongoing risks of HIV acquisition for this vulnerable population. Clinical trial registration ClinicalTrials.gov, number NCT02550067 was the main Clinical Trial from which this secondary, non-randomized / observational analysis was derived with data limited to just South African sites.
Laura Danielle Wagner, Alexandra M. Minnis, Jaclyn Shea, Kawango Agot, Khatija Ahmed, and Ariane van der Straten
Public Library of Science (PLoS)
Background Male partner awareness and acceptance of microbicide and family planning product use has been shown to increase women’s own acceptance and adherence of a product. However, little is known about preferences regarding potential Multipurpose Prevention Technology (MPT) product delivery forms. As part of the TRIO study, men’s reactions to their female partner’s TRIO product use and comparisons of men’s and women’s views of TRIO product attributes and use acceptability were explored to better understand product preferences. Methods Women in TRIO used three placebo products that represented potential MPTs: daily oral tablets, monthly vaginal rings, and monthly dual injections. Male partners (N = 39) and women (N = 88) completed in-depth interviews on their own and their partner’s experiences with these products. Qualitative coding and analyses followed a conceptual model of HIV prevention product acceptability, and here, we explored themes of disclosure, trust and infidelity as they informed barriers and facilitators to product use. Results Men expressed a desire to know of their partner’s product use decisions and be informed and educated on the products to better support their partners, in some cases, expressing a high level of concern regarding maximizing the ease of product adherence for their partner. They also wanted to understand the effects of products on sexual encounters with their partner, but in some cases, wanted more knowledge in order to control their partner’s product use decisions. Similarly to women, men found long-acting, discreet products that have little to no effect on sexual encounters or libido the most acceptable for their female partners’ use. Product use was most acceptable to men if they were informed of use without inadvertent discovery. Conclusions Men’s product attribute preferences often aligned with women’s opinions of the same products. To support women’s correct use of MPTs, further research is needed to determine the best strategy for achieving male partner acceptance and support of product use, particularly for less familiar delivery forms, such as the vaginal ring.
Shabir A Madhi, Dhayendre Moodley, Sherika Hanley, Moherndran Archary, Zaheer Hoosain, Umesh Lalloo, Cheryl Louw, Lee Fairlie, Leon Frederik Fouche, Mduduzi S L Masilela,et al.
Elsevier BV
Linda-Gail Bekker, Nigel Garrett, Ameena Goga, Lara Fairall, Tarylee Reddy, Nonhlanhla Yende-Zuma, Reshma Kassanjee, Shirley Collie, Ian Sanne, Andrew Boulle,et al.
Elsevier BV
Robert S. Wallis, Sibuse Ginindza, Trevor Beattie, Nishanee Arjun, Morongwe Likoti, Modulakgotla Sebe, Vinodh A. Edward, Mohammed Rassool, Khatija Ahmed, Katherine Fielding,et al.
Public Library of Science (PLoS)
Background Current tuberculosis treatments leave most patients with bronchiectasis and fibrosis, permanent conditions that impair lung function and increase all-cause post-TB mortality. Host-directed therapies (HDTs) may reduce lung inflammation and hasten eradication of infection. Biomarkers can accelerate tuberculosis regimen development, but no studies have yet examined early biomarkers of TB-HDTs. Methods Biomarkers of inflammation and microbicidal activity were evaluated as a part of a recent phase-2 randomized controlled trial of four HDTs in 200 patients with pulmonary tuberculosis and baseline predictors of poor outcome, including CC-11050 (PDE4i), everolimus (mTORi), auranofin (oral gold salt), and ergocalciferol (vitamin D). Two of the 4 arms (CC-11050 and everolimus) showed superior recovery of lung function at day 180 compared to control; none showed accelerated eradication of MTB infection. Patients underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) on entry and day 56. PET signals were analyzed according to total, maximal, and peak glycolytic activity; CT was analyzed according to total modified Hounsfield units to assess radiodensity. Mycobactericidal activity in ex vivo whole blood culture was measured on days 42, 84, and 140. C-reactive protein (CRP) was measured at multiple time points. Results All PET/CT parameters showed highly significant reductions from baseline to day 56; however, only maximal or peak glycolytic activity showed further experimental reduction compared to controls, and only in everolimus recipients. CRP dropped precipitously during early treatment, but did so equally in all arms; over the entire period of treatment, the rate of decline of CRP tended to be greater in CC-11050 recipients than in controls but this fell short of statistical significance. Whole blood mycobactericidal activity in ex-vivo culture was enhanced by auranofin compared to controls, but not by other HDTs. Conclusions None of these early biomarkers correctly predicted HDT effects on inflammation or infection across all four experimental arms. Instead, they each appear to show highly specific responses related to HDT mechanisms of action.
Katlego Mapetla, Mookho Malahleha, Nadia van Niekerk, Dineo Thindisa, Lebogang Mpete, Khatija Ahmed, and Athmanundh Dilraj
SAGE Publications
Background Ensuring protocol visit compliance and maintaining high participant retention remain critical elements of clinical trials. In the HVTN 702 HIV vaccine trial, Setshaba Research Centre in Soshanguve, Tshwane, South Africa, experienced challenges in communicating with participants to remind them about their study visits. In order to improve participants adhering to their study visits, and study retention, we aimed to identify challenges in mobile communication, and to establish preferences in communication methods and interest in receiving study information via cellphones. Methods We conducted a paper-based survey among HVTN 702 HIV vaccine trial participants at Setshaba Research Centre. The survey comprised of dichotomous and scale questions and was completed voluntarily and anonymously. The questions included those on their primary form of communication (calling, SMS and WhatsApp), the best time of day for the site to communicate with them, whether they were interested in receiving regular general study information updates via their cellular phone, how often they changed their cellular phones and/or network, whether they experienced any challenges with their cellular phones and what these challenges were, if any. All participants scheduled to visit the clinic from February to May 2019 were invited to participate. Thus, 90 of 380 (24%) participants enrolled by May 2019 were surveyed. Results The majority (68%) of participants were 26−35 years old and almost three-quarters (73%) were female. Almost all participants (99%) had a personal cellphone. Half of the participants experienced some challenge related to cellphones, these being poor network signal at home (12%), battery running flat frequently (11%), sharing their phone (9%), lack of data (9%), challenges with use of applications (6%) and their cellphones being unreliable (3%). Annually, 20% of participants made a single or multiple network changes. Communication preferences were calls by site staff (80%), SMS (16%) and WhatsApp (3%). Most preferred to be contacted in the morning (49%) or afternoon (31%). Site contact was rated as ‘very helpful’ (87%), and 97% were interested in receiving regular general study information updates via their cellphone. Conclusion Despite participants owning cellphones, there are still technical challenges, for example, network signals, battery-charging and applications. The majority of participants preferred being called rather than communicating by text messages or WhatsApp. Future studies need to include addressing participant challenges in maintaining contact and training of participants on use of cellphone applications to optimise communication. Noting the preferred time of day for participants to be called might improve the likelihood of making contact with them. The willingness to receive updates will aid in keeping participant interest high and enhance retention.