Training the next generation of Biostatisticians in West Africa: The Vanderbilt Nigeria Biostatistics Training Program (VN-BioStat).

Biomedical HIV research is growing in West Africa, but biostatistical expertise is lagging. The Vanderbilt-Nigeria Biostatistics Training Program (VN-BioStat) seeks to establish a research and training platform for biostatisticians doing HIV-related research in Nigeria. The objectives of the program are: 1) Host two Nigerian data scientists per year (a total of 10 over 5 years) at Vanderbilt University Medical Center to gain hands-on biostatistics training and experience via one-year fellowships. Eligible trainees will be junior investigators with PhDs or nearing completion of their PhDs in statistics or related fields, including mathematics and computer science. 2) Conduct annual workshops in Nigeria to provide biostatistics training. Trainees will undertake biostatistics coursework and hands-on training and participate in mentorship as biostatisticians involved in HIV research. Trainees will be at Vanderbilt for a full year and be part of an active biostatistics department. They will be immersed in a dry-lab HIV biostatistics project in collaboration with a Nigerian HIV research project and lead a methodologically focused research project. They will also participate in a one-month research training/grant writing program in Nashville. The VN-BioStat program will build on the existing momentum of ongoing initiatives to enhance research capacity in Nigeria by developing biostatistics leadership. VN-BioStat trainees will interact with investigators from Nigeria to provide collaborative biostatistical assistance with study design and data analysis, thus gaining real-world experience that will benefit the trainees and the broader research community in Nigeria.

Strengthening research capacity through an intensive training program for biomedical investigators from low- and middle-income countries: the Vanderbilt Institute for Research Development and Ethics (VIRDE).

BACKGROUND: Capacity strengthening initiatives aimed at increasing research knowledge and skills of investigators in low- and middle-income countries (LMICs) have been implemented over the last several decades. With increased capacity, local investigators will have greater leadership in defining research priorities and impact policy change to help improve health outcomes. Evaluations of models of capacity strengthening programs are often limited to short-term impact. Noting the limitations of traditional output-based evaluations, we utilized a broader framework to evaluate the long-term impact of the Vanderbilt Institute in Research Development and Ethics (VIRDE), a decade-old intensive grant development practicum specifically tailored for investigators from LMICs. METHODS: To assess the impact of VIRDE on the research careers of alumni over the past 10 years, we surveyed alumni on research engagement, grant productivity, career trajectory, and knowledge gained in grant writing. Descriptive statistics, including means and total counts, and paired sample t-tests were used to analyze the data. RESULTS: Forty-six of 58 alumni completed the survey. All respondents returned to their home countries and are currently engaged in research. Post-VIRDE grant writing knowledge ratings were significantly greater than pre-VIRDE. The number of respondents submitting grants post-VIRDE was 2.6 times higher than before the program. Eighty-three percent of respondents submitted a total of 147 grants post-VIRDE, of which 45.6% were awarded. Respondents acknowledged VIRDE's positive impact on career growth and leadership, with 88% advancing in career stage. CONCLUSIONS: Gains in grant writing knowledge and grant productivity suggest that VIRDE scholars built skills and confidence in grant writing during the program. A substantial proportion of respondents have advanced in their careers and continue to work in academia in their country of origin. Results show a sustained impact on the research careers of VIRDE alumni. The broader framework for research capacity strengthening resulted in an expansive assessment of the VIRDE program and alumni, illuminating successful program elements and implications that can inform similar capacity strengthening programs.

The V-RAMP Program: Building Research Administration and Management Capacity in Nigeria.

The increasing volume and complexity of research activities in Nigeria necessitates urgent measures to improve research infrastructure in grants administration and management. The Vanderbilt-Nigeria Research Administration and Management Training Program (V-RAMP) seeks to build infrastructure capacity in research administration and management and research ethics at a major teaching hospital in Nigeria. We will perform a mixed methods needs assessment of the administrative and management environment and develop an action plan to address infrastructure needs, prioritize processes, and guide program implementation. We will capacitate a newly established Office of Research Administration and improve the knowledge and skills of research administrators and grant managers via short term in-person trainings in Nashville, Tennessee and in Kano, Nigeria and through remote learning opportunities. We will enhance local administrative efficiency and performance of research ethics operations through training and mentoring of members and staff of the ethics review committee. Systematic processes to streamline protocols, including a REDCap protocol tracking database and standard operating procedures in the responsible conduct of research and rigor and reproducibility will also be developed. V-RAMP will enable the creation of a high-quality research administration environment that is knowledgeable, efficient, and compliant regarding the fiscal, management and ethical standards of sponsored research.

Capacity Building for Primary Stroke Prevention Teams in Children Living With Sickle Cell Anemia in Africa.

BACKGROUND: Nigeria has the highest proportion of children with sickle cell anemia (SCA) globally; an estimated 150,000 infants with SCA are born annually. Primary stroke prevention in children with SCA must include Nigeria. We describe capacity-building strategies in conjunction with two National Institutes of Health-funded primary stroke prevention trials (a feasibility trial and phase III randomized controlled trial) with initial hydroxyurea treatment for children with SCA and abnormal transcranial Doppler (TCD) velocities in Nigeria. We anticipated challenges to conducting clinical trials in a low-resource setting with a local team that had not previously been involved in clinical research and sought a sustainable strategy for primary stroke prevention. METHODS: This is a descriptive, prospective study of challenges, solutions, and research teams in two trials that enrolled a total of 679 children with SCA. RESULTS: As part of the capacity-building component of the trials, over eight years, 23 research personnel (physicians, nurses, research coordinators, a statistician, and a pharmacist) completed a one-month research governance and ethics training program at Vanderbilt University Medical Center, USA. A lead research coordinator for each site completed the Society of Clinical Research Professionals certification. TCD machines were donated; radiologists and nonradiologists were trained and certified to perform TCD. A scalable E-prescription was implemented to track hydroxyurea treatment. We worked with regional government officials to support ongoing TCD-based screening and funding for hydroxyurea for children with SCA at a high risk of stroke. CONCLUSIONS: Our trials and capacity building demonstrate a sustainable strategy to initiate and maintain pediatric SCA primary stroke prevention programs in Africa.

Systematic Review of Cancer Research Output From Africa, With Zambia as an Example.

PURPOSE: Cancer occurrence is increasing in Africa, although research has lagged. The objective of this review was to analyze cancer research outputs from Africa, with a particular focus on Zambia. METHODS: We searched PubMed for published cancer-related articles from African countries. All articles reporting on cancer in Africa were considered. We conducted analyses to explore correlations between cancer research output and total population, gross domestic product, and new cancer cases recorded in 2020. For Zambia articles, we also analyzed cancer types and time trends. RESULTS: A total of 48,487 cancer-related publications from Africa were identified, with nearly half coming from Egypt (13,372; 28%) and South Africa (9,393; 19%). Cancer research output correlated significantly with country population (Spearman's correlation coefficient 0.74; P < .001) and the number of new cancer cases recorded in 2020 (Spearman's correlation coefficient 0.77; P < .001). Standardized by population size, Western Sahara (0.576), Seychelles (0.244), Tunisia (0.239), South Africa (0.158), and Egypt (0.131) had the highest overall output per 1,000 population. A total of 244 publications were from Zambia; the most studied cancers were cervical (25%), Kaposi sarcoma (24%), and breast (10%). Although an increase in cancer research output from Zambia was noted, only 33% of publications were first or last authored by Zambians. The major limitation of this review is that the evaluation was based on a single electronic database, PubMed. CONCLUSION: Cancer research output from Africa is very low, with many of the publications concentrated in a few countries. There is an urgent need to invest in both human resources and infrastructure to increase cancer research output from African countries, particularly in less populous countries.

Primary prevention of stroke in children with sickle cell anemia in sub-Saharan Africa: rationale and design of phase III randomized clinical trial.

Strokes in children with sickle cell anemia (SCA) are associated with significant morbidity and premature death. Primary stroke prevention in children with SCA involves screening for abnormal transcranial Doppler (TCD) velocity coupled with regular blood transfusion therapy for children with abnormal velocities, for at least one year. However, in Africa, where the majority of children with SCA live, regular blood transfusions are not feasible due to inadequate supply of safe blood, cost, and the reluctance of caregivers to accept transfusion therapy for their children. We describe the Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria Trial [StrokePreventioninNigeria (SPRING) trial, NCT02560935], a three-center double-blinded randomized controlled Phase III clinical trial to 1) determine the efficacy of moderate fixed-dose (20 mg/kg/day) versus low fixed-dose (10 mg/kg/day) hydroxyurea therapy for primary stroke prevention; 2) determine the efficacy of moderate fixed-dose hydroxyurea for decreasing the incidence of all cause-hospitalization (pain, acute chest syndrome, infection, other) compared to low fixed-dose hydroxyurea. We will test the primary hypothesis that there will be a 66% relative risk reduction of strokes in children with SCA and abnormal TCD measurements, randomly allocated, for a minimum of three years to receive moderate fixed-dose versus low fixed-dose hydroxyurea (total n = 220). The results of this trial will advance the care of children with SCA in sub-Saharan Africa, while improving research capacity for future studies to prevent strokes in children with SCA.

HIV Research Training Partnership of the University of Zambia and Vanderbilt University: Features and Early Outcomes.

Background: Despite the burden of HIV being highest in sub-Saharan Africa (SSA), research expertise and capacity to address scientific questions regarding complications of HIV and ART, especially chronic non-communicable conditions, is limited in the region. The comorbidities prevalent in persons with HIV are mediated through diverse mechanisms, many of which can be context or region-specific and are yet to be elucidated. The phenotype, risk factors, and effective interventions for these conditions may differ between populations and settings, and therefore there is an urgent need for research to help understand these processes and how to best address them in SSA. Here, we report the research capacity building activities in SSA conducted by the University of Zambia (UNZA)-Vanderbilt Training Partnership for HIV-Nutrition-Metabolic Research (UVP), drawing lessons and challenges for a wide global health audience. Methods: We reviewed program data and conducted interviews with program leaders and participants to understand and document the progress and outcomes of the partnership. We report the program's early achievements, highlighting drivers and challenges. Results: Between 2015 and 2019, UVP made substantial progress on its goals of training new UNZA PhD scientists to investigate complex nutritional and metabolic factors related to long-term HIV complications and comorbidities. The program has supported 11 UNZA PhD students with dual UNZA-Vanderbilt mentorship; three have graduated, and other candidates are progressing in their PhD studies. The project also supported institutional capacity through UNZA faculty participation in Vanderbilt grant writing workshops, with strong success in obtaining grants among those who participated. UVP also supported development of greater structure to UNZA's PhD program and a mentorship curriculum, both now adopted by UNZA. The major drivers for success included UVP's alignment of goals between UNZA and Vanderbilt, and local institutional ownership. The longstanding history of collaborations between the two institutions contributed substantially to alignment and mutual support of UVP's goals. Several challenges were noted, including limits on direct research funding for students and a relatively small pool of funded investigators at UNZA. Conclusions: Despite some challenges, UVP has achieved positive outcomes over its first four years. Longstanding partnerships and local institutional ownership were the main drivers. We expect the challenges to mitigated as the project continues and produces more UNZA researchers and teams and more funded projects, collectively building the local research community. With continued resources and clear focus, we expect that UNZA's investigators and partners will attract research funding and generate high-impact research outputs across a broad range of studies in HIV as well as newer threats from non-communicable conditions experienced by long-term survivors of HIV and by the general population.

Methadone maintenance therapy and HIV counseling and testing are associated with lower frequency of risky behaviors among injection drug users in China.

Three consecutive cross-sectional surveys were conducted among injection drug users (IDUs). Of 2,530 participants, 47.7% reported ever sharing needles, 78.2% having had unprotected sex in the last month, 34.4% not receiving either methadone maintenance therapy (MMT) or HIV voluntary counseling and testing (VCT), 4.8% ever receiving MMT-only, 36.6% ever receiving VCT-only, and 24.2% ever receiving both MMT and VCT. MMT-only and the combination of MMT and VCT had significant associations with needle sharing and on unprotected sexual behaviors. Effectively integrating VCT into MMT services is a logical way to maximize the impact of both interventions on risky behaviors among IDUs.

Current drug use and lack of HIV virologic suppression: point-of-care urine drug screen versus self-report.

BACKGROUND: There have been inconsistent findings on the association between current drug use and HIV disease progression and virologic suppression. Drug use was often measured using self-report of historical use. Objective measurement of current drug use is preferred. METHODS: In this cross-sectional study, we assessed drug use through Computer-Assisted Self Interviews (CASI) and point-of-care urine drug screen (UDS) among 225 HIV-infected patients, and evaluated the association between current drug use and virologic suppression. RESULTS: About half (54%) of participants had a positive UDS, with a lower self-reported rate by CASI (42%) (Kappa score = 0.59). By UDS, 36.0% were positive for marijuana, 25.8% for cocaine, 7.6% for opiates, and 2.2% for methamphetamine or amphetamine. Factors associated with virologic suppression (plasma HIV RNA <50 copies/mL) were Caucasian race (P = 0.03), higher CD4 count (P < 0.01), current use of antiretroviral therapy (ART) (P < 0.01), and a negative UDS (P < 0.01). Among 178 current ART users, a positive UDS remained significantly associated with lower likelihood of virologic suppression (P = 0.04). CONCLUSIONS: UDS had good agreement with CASI in detecting frequently used drugs such as marijuana and cocaine. UDS at routine clinic visits may provide "real-time" prognostic information to optimize management.

Translation of biomedical prevention strategies for HIV: prospects and pitfalls.

Early achievements in biomedical approaches for HIV prevention included physical barriers (condoms), clean injection equipment (both for medical use and for injection drug users), blood and blood product safety, and prevention of mother-to-child transmission. In recent years, antiretroviral drugs to reduce the risk of transmission (when the infected person takes the medicines; treatment as prevention) or reduce the risk of acquisition (when the seronegative person takes them; preexposure prophylaxis) have proven to be efficacious. Circumcision of men has also been a major tool relevant for higher prevalence regions such as sub-Saharan Africa. Well-established prevention strategies in the control of sexually transmitted diseases and tuberculosis are highly relevant for HIV (ie, screening, linkage to care, early treatment, and contact tracing). Unfortunately, only slow progress is being made in some available HIV-prevention strategies such as family planning for HIV-infected women who do not want more children and prevention of mother-to-child HIV transmission. Current studies seek to integrate strategies into approaches that combine biomedical, behavioral, and structural methods to achieve prevention synergies. This review identifies the major biomedical approaches demonstrated to be efficacious that are now available. We also highlight the need for behavioral risk reduction and adherence as essential components of any biomedical approach.

Effectiveness of integrated HIV prevention interventions among Chinese men who have sex with men: evaluation of a 16-city public health program.

To examine the impacts of a multi-city HIV prevention public health program (China Global Fund Round 5 Project) on condom use and HIV infection, we analyzed four yearly cross-sectional surveys from 2006 through 2009 among 20,843 men who have sex with men (MSM) in 16 Chinese cities. Self-reported condom use at last sex with a male partner increased from 58% in 2006 to 81% in 2009 (trend test, P<0.001). HIV prevalence increased from 2.3% in 2006 to 5.3% in 2009 (P<0.001). Multivariable logistic regression analysis showed that self-reported receipt of interventions was an independent predictor of increased condom use at last sex with a male partner over time (adjusted odds ratio [aOR], 1.63 in 2006 to 2.33 in 2009; P<0.001), and lower HIV prevalence (aOR, 1.08 in 2006 to 0.45 in 2009; P<0.001). HIV prevalence increased from 2006-2009 for participants with no self-reported receipt of interventions (2.1% in 2006 to 10.3% in 2009) and less so for those with interventions (2.4% to 4.7%). This Chinese public health program had positive impacts on both behaviors and disease rate among MSM population. Escalation of the coverage and intensity of effective interventions is needed for further increasing condom use and for reversing the rising trend of HIV epidemic.

Condom use during commercial sex among clients of Hijra sex workers in Karachi, Pakistan (cross-sectional study).

Objective To describe the prevalence and predictors of condom use and sexual risk in the male clients of Hijra sex workers (HSWs) in Karachi, Pakistan. Design Cross-sectional study. Setting Karachi, Pakistan. Participants Clients of HSWs were recruited with assistance from HSWs and a non-governmental organisation (NGO) focused on men who have sex with men (MSM) during October-November 2010. Measurements The interviewer administered the questionnaire to each participant to solicit information on demographics, HIV/AIDS knowledge/attitudes and sexual risk behaviours/practices, including condom use in the last sexual act with the HSW. Results Of the 203 participants, 42.4% reported that they used condoms during their last sexual act with HSW, 40% were married, 18% had ever used drugs or alcohol, and 52% reported also engaging with female sex workers in the last month. Casual HSW clients were more likely to use condoms than regular clients (adjusted OR (AOR), 2.50; 95% CI 1.34 to 4.65), as were persons with a higher education level (AOR 5.8; 95% CI 1.6 to 20.3). Drug/alcohol users and non-users were equally likely to use condoms (AOR 1.11; 95% CI 0.51 to 2.24). Conclusion Clients of HSWs in Pakistan are at risk of acquiring HIV/STI infections. Concerted efforts are needed to increase condom use in this key bridge population to curtail the spread of HIV in the general population.

Prevalence of HIV infection and predictors for syphilis infection among female sex workers in southern China.

The purpose of this study was to assess the prevalence and risk factors for syphilis infection among female sex workers (FSWs) in Liuzhou City, Guangxi Zhuang Autonomous Region, southern China. A cross-sectional study recruited FSWs using a venue-based method and subsequent snowball sampling with mapping strategies. Questionnaire-based interviews were conducted to collect demographic and behavioral information. Blood was tested for syphilis (RPR with TPPA confirmation) and HIV (EIA with Western blot confirmation) infections. Of the 362 eligible participants, 81.7% were non-local residents (60.5% from other parts of Guangxi and 21.2% were non-Guangxi residents); 58.0% belonged to non-Han minority ethnic groups; 37.5% reported inconsistent condom use with their clients and 71.2% reported inconsistent condom use with their regular sex partners during the past month. Nearly 10% reported having had sex with drug users. The prevalence rates for HIV and syphilis infections were 2.3% and 11.0%, respectively. Almost half (46.6%) of participants reported having had STD symptoms. Inconsistent condom use with clients in the past month (AOR = 5.0; 95% CI = 1.8-13.8), less education (OR = 2.6; 95% CI = 1.1-7.4), and HIV infection (AOR = 8.1; 95% CI = 1.1-68.5) were independently associated with syphilis infection.

Impact of methadone on drug use and risky sex in China.

This study examined the impact of methadone on drug-using and risky sexual behaviors among 557 heroin injection drug users in one of the first methadone programs in China. Structured questionnaires were administered to collect data on methadone utilization, drug use, and risky sexual behaviors. Blood samples were tested for blood-borne infections. Multivariate logistic analyses revealed that, among opioid-addicted individuals, methadone participants were less likely to use or inject drugs and share needles than nonparticipants. They also were less likely to have multiple sexual partners or have unprotected sex. Those currently enrolled in methadone maintenance had lower risk of using and injecting drugs than those who were no longer receiving methadone. Data suggest positive, short-term impact on these important behaviors, but further studies are needed to examine the long-term impact of methadone treatment on disease rates.