Engaging in clinical trials in Africa not only enhances researchers' comprehension of local health concerns but also plays a crucial role in tackling global health challenges. In Tanzania, there has been a surge of clinical research for the past 10 years indicating a need to improve ethical and clinical trial regulatory capacity. Several initiatives to address the clinical trial regulatory and ethics challenges have been done. Lessons from such initiatives are important to inform evidence-based decision-making for sustainability. The ASCEND project with the theme of “Moving Tanzania’s Clinical Research Ethics and Medicines Regulatory Capacity to the Next Level: Fostering Medicine Quality, Safety and Good Clinical Practice (GCP) on Clinical Trials” was implemented in Tanzania Mainland and Zanzibar from November 2020 to December 2023. A thorough review of the project implementation reports and on deliverables was conducted to identify the lessons learned. Inductive content analysis was used to analyze the information. A total of seven lessons were deduced from the reviewed documents. These include capacity building through training on clinical trials review and approval process, research ethics and GCP inspection which cannot be overlooked; engaging the community in reporting adverse drug events is worth considering; digitalization of electronic systems enhances clinical trial control and creates a dynamic regulatory ecosystem; compliance to requirements for clinical trials conduct is enhanced by training of early and mid-career researchers; networking and broad stakeholders’ engagement and participation in ethics and regulations governing clinical trials is a cornerstone for strengthening collaboration between researchers and regulators; the need for electronic systems for monitoring and evaluation of the project is inevitable and the need for adhering to project timelines is crucial for successful implementation of the project. Sustainability is the take-home message from the ASCEND project and should inform stakeholders for future improvement. Continuous investment and advancement in research ethics and regulatory oversight across Africa should be prioritized.

Objective: Cervical cancer is a common preventable cancer among African women living with HIV (WLWH). Molecular diagnostics for high-risk human papillomavirus (HR-HPV) genotypes are standard components of cervical cancer screening in resource-rich countries but not in resource-limited settings. We evaluated HR-HPV genotypes among women with and without HIV in four African countries to inform cervical cancer preventive strategies. Methods: The African Cohort Study (AFRICOS) enrolled participants with and without HIV at 12 clinics in Tanzania, Kenya, Uganda, and Nigeria. Cervical cytobrush specimens from women were genotyped for 14 HR-HPV types using the multiplex Seegene Anyplex real-time PCR assay. Robust Poisson regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for factors associated with HR-HPV in WLWH. Results: From January 2015 to March 2020, 868 WLWH and 134 women living without HIV (WLWoH) were tested for HR-HPV with prevalence of 50.9 and 38.1%, respectively (P = 0.007). Among WLWH, 844 (97.4%) were antiretroviral therapy (ART)-experienced and 772 (89.7%) virally suppressed 1000 copies/ml or less. The most frequent HR-HPV types among WLWH were HPV-16 (13.5%), HPV-52 (9.5%), and HPV-35 (9.3%). HR-HPV infection was more common among Tanzanian WLWH (adjusted RR: 1.23, 95% CI 1.05–1.44, P = 0.012). Also, WLWH with CD4+ T cells of less than 200 cell/μl had 1.51-fold increased risk of having HR-HPV (95% CI 1.23–1.86, P < 0.001). Conclusion: HR-HPV was common in WLWH in four African countries, particularly among women with low CD4+ cell count. Scale up of HPV vaccines and development of vaccines with broader activity against less common HR-HPV types may improve cervical cancer prevention in Africa.

Background Sexually transmitted infections (STIs) are common among young people in low- and middle-income countries and are associated with negative reproductive and pregnancy outcomes. Most of the studies have assessed HIV among adolescents and young adults, with limited information on occurrence of other STIs in this population. This study aimed to describe the prevalence of and risk factors associated with Herpes Simplex Virus-type 2 (HSV-2), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Syphilis and HIV infection among young adults attending Higher Learning Institutions (HLIs) in Mbeya, Tanzania. Methods We conducted a cross-sectional study among students aged 18-24years attending HLIs in Mbeya-Tanzania, randomly selected using a computerized random number. Participants were tested for HSV-2, CT, NG, Syphilis and HIV infection. We used a self-administered questionnaire to collect information on sexual activity and risk factors to the tested STIs. Results We enrolled 504 students from 5 HLIs, with mean age of 21.5 years (SD 1.7). 17% of the students had at least one STI; prevalence was higher among females than males (21.1% versus 14.1%). CT (11%) and HSV-2 (6.1%) were the most common STIs, while NG (1.1%) and HIV (0.7%) infection had the least occurrence. None of the participants was diagnosed with Syphilis. In univariate analysis, predictors for STIs were Sex, inconsistent condom use in the past 4weeks, report of oral sex, sexual orientation (bisexual/homosexual) and having a sexual partner with an age-difference of at least 5years (either older or younger); while in the multivariate analysis, Sex, inconsistent condom use in the past 4weeks and sexual orientation (bisexual/homosexual) remained significant. Conclusion STIs such as Chlamydia and HSV-2 which are commonly asymptomatic are of concern among young adults attending HLIs. The latter is an important group that needs attention and recognition that is pivotal in transmission of STIs considering their risk. Information, Education and Communication (IEC) campaigns targeting young adults, especially those at HLIs, need to focus on exposure-risk minimization. Funding institutions that have invested heavily on HIV prevention campaigns should consider giving similar recognition to other STIs for a streamlined outcome.

Introduction/Background Cervical cancer (CxCa) and its precursor lesions are caused by persistent infection with a high-risk(HR) Human Papillomavirus (HPV). Women living with HIV (WLWH) have a higher risk for cervical dysplasia and CxCa development. The high HPV prevalence in WLWH makes a HPV-PCR based screening non-efficient. Biomarker detection could be a possibility, to find woman at risk. We evaluated the biomarker-based QuantiGene-Molecular-Profiling-Histology assay (QG-MPH) in WLWH. Methodology We analysed a representative subset of samples (n=301) from the prospective 2H-study including HIV+ and HIV- women. A cervical sample was collected using a cytobrush and fixed into ThinPrep/PreservCyt. The QG-MPH assay is based on the multiplexed Luminex bead-based technology platform (QuantiGene 2.0). It detects and quantifies the mRNA of 18 HR-HPV genotype-specific oncogenes, reference genes and cellular biomarkers including proliferation, tumour stem cell and tumour markers to predict the dysplasia stage, simultaneously. Results HIV coinfection was significantly associated with increased mRNA expression of the following biomarkers in HR-HPV+ women without cervical lesions: leading HPV-E7 (p=0.0019), p16 (p=0.022), STMN1 (p=0.0039), MCM2 (p=0.015), KRT7 (p=0.0035) and KRT17 (p=0.014). In cervical cancer cases (HIV+=19, HIV-=18) only the expression of Nanog mRNA was different (p=0.022). Using the risk score developed on a HIV- cohort led to false positive detection (CIN3+) of 68.8% (n=22) in WLWH without lesions. Logistic regression analyses showed best markers for CxCa detection in HIV+ patients in our cohort were BIRC5, KRT17, MMP7 and p53 with a combined AUC of 0.93 (sensitivity=95%, specificity=82.0%). Conclusion Viral oncogene expression is increased in HR-HPV+ WLWH without cervical lesions. Biomarker evaluation has the potential to overcome problems of HPV PCR-based screening in WLWH. However, risk score adaptation is needed as biomarker expression varies between HIV+ and HIV- patients. Further studies with higher sample number are warranted to confirm the best markers and risk scores by QG-MPH analysis.

HIV-care programmes are faced with significant challenges in getting newly diagnosed People Living with Human Immunodeficiency Virus (PLHIV) linked to care despite massive investment in HIV prevention, treatment and care. This study assessed the performance of mobile HIV Testing and Counseling service (mHTC) in provision of HIV-testing and linkage to care of newly diagnosed PLHIV from Key and Vulnerable Populations (KVPs). A retrospective review of the records of 25,248 clients was extracted from the mHTC database from October-2016 to September-2018. Of 25,248 clients, 51.71% were in 25-45 years age group, 55.4% were males, 60.5% were married and 62.1% had primary level of education. The median age of clients was 31 (IQR: 23-42) years. Out of the clients tested, 800 (3.17%) were diagnosed HIV-positive. Positivity was high among females 450 (4%), age group 25-45 years 538 (4.12%), divorced 202 (7.41%) and clients with primary level of education 504 (3.21%). An association between HIV status and sex, age group, relationship status and level of education was observed (P<0001). Out of the 800 HIV-positive clients, 418 (52.30%) were successfully linked to care. Among the positive clients, 5/6 (83.33%) children below 15 years old, 238/450 (52.89%) females and 39/64 (60.94%) widows were successfully linked to care. In the multivariable log binomial regression model age of the clients was associated with successful linkage to care. The mHTC was able to reach KVP clients; overall linkage for both sexes was 52.30% below the recommended UNAIDS 90-90-90 target. Raising the need to address the challenges associated with linkage and specific care for KVPs as a subset of the general population. The mHTC has shown that it is feasible to improve the reach of KVP clients; however, further research is required to examine the quality of this service at the community level.

Abstract Background Worldwide 85% of cervical cancer (CC) related deaths occur in low- and middle-income countries. Sub-Saharan Africa is burdend by an overlapping high incidence of CC as well as HIV infection, a risk factor for HPV associated disease progression. Recent upscaling of CC screening activities increased the number of CC diagnoses in a previous unscreened population. The aim of the 2H study was to follow up on women with CC in the context of available health care services in Tanzania in relation to their HIV infection status. Methods This longitudinal observational cohort study included women with histological confirmed CC from Mbeya, Tanzania, between 2013–2019. All women were referred for CC staging and cancer-directed therapies (CDT), including surgery and/or radio-chemotherapy, or palliative care. Annual follow-up focused on successful linkage to CDT, interventions and survival. We assessed factors on compliance, used Kaplan–Meier-Survivor functions to evaluate survival time and poisson regression models to calculate incidence rate ratios on mortality (IRR) two years after diagnosis. Results Overall, 270 women with CC (123 HIV infected) were included. Staging information, available in 185 cases, showed 84.9% presented with advanced stage disease (FIGO ≥ IIB), no difference was seen in respect to HIV status. HIV-infected women were 12 years younger at the time of cancer diagnosis (median age 44.8 versus 56.4 years, p < 0.001). Median follow up period was 11.9 months (range 0.2–67.2). Survival information, available in 231 cases, demonstrated for women diagnosed in early-stage disease a median survival time of 38.3 months, in advanced-stage 16.0 months and late-stage disease 6.5 months after diagnosis. Of all women, 42% received CDT or palliative support. HIV co-infection and education were associated with higher health care compliance. CDT was significantly associated with lower 2-year mortality rates (IRR 0.62, p = 0.004). HIV coinfection did not impact mortality rates after diagnosis. Conclusion High numbers of advanced and late staged CC were diagnosed, compliance to CDT was low. A beneficial impact of CDT on CC mortality could be demonstrated for local health care services. This study indicates challenges for successful linkage and supports an effective scale up of cancer care and treatment facilities.

Background High-risk sexual behaviors(HRSBs) among young adults are key risk for Sexually Transmitted Infections(STIs), HIV and unplanned pregnancies. WHO has identified the 15-24years age-group as high-risk for STIs. Students at Higher Learning Institutions(HLIs) may be at higher risk because they are free of immediate parental-supervision, are a transient migratory population, probably at peak-years of sexual activity. In Tanzania, information is limited on sexual and preventive behaviours among young adults in HLIs. We describe risky sexual behaviours and preventive practices among young adults attending HLIs in Mbeya-Tanzania. Methods We conducted a cross-sectional study from March2019 to January2020 among randomly selected students aged 18-24years enrolled in HLIs within Mbeya. Probability proportional to size was used to determine total student number from each HLI. We used a self-administered questionnaire to collect information on sexual health education, activity, behaviour and STI knowledge. Results Total of 504students were enrolled with mean age of 21.5(SD 1.74)years. Total of 446(88.5%) students reported ever having had sex. Mean-age at first sex was 18.4years and 9.9% reported sexual debut <15years. A higher proportion of male students(57%) reported sexual debut with non-steady partners than females(37.9%). Lack of condom use at sexual debut was reported by 52% of the participants. Consistent condom use during past 4-weeks was reported at 33% and 16.5% among males and females, respectively. About 1 in 10 students reported forced sex by someone they were dating. Sex under the influence of alcohol was reported by 24% of the students. Nearly 8 in 10 (78.7%) students have heard of STIs, but only 16% were aware STIs can be asymptomatic. Conclusion STI prevention programs need to recognize young adults in HLIs as at-risk population; and advocate targeted messages to minimize risk to acquiring STIs, counseling and support for those experiencing sexual violence, promote condom use and safer-sex negotiation skills.

BackgroundWomen living with HIV in sub-Saharan Africa are at increased risk to develop cervical cancer (CC), which is caused by persistent infection with 13 oncogenic human papilloma viruses (HR-HPVs). It is important to accurately identify and target HIV-positive women at highest risk to develop CC for early therapeutic intervention.MethodsA total of 2,134 HIV+ and HIV− women from South-West Tanzania were prospectively screened for cervical cancer and precancerous lesions. Women with cervical cancer (n=236), high- and low-grade squamous intraepithelial lesions (HSIL: n=68, LSIL: n=74), and without lesion (n=426) underwent high-resolution HPV genotyping.ResultsEighty percent of women who were diagnosed with HSIL or LSIL were living with HIV. Any lesion, young age, HIV status, and depleted CD4 T cell counts were independent risk factors for HPV infections, which were predominantly caused by HR-HPV types. While multiple HR-HPV type infections were predominant in HIV+ women with HSIL, single-type infections predominated in HIV+ CC cases (p=0.0006). HPV16, 18, and 45 accounted for 85% (68/80) and 75% (82/110) of HIV+ and HIV− CC cases, respectively. Of note, HPV35, the most frequent HPV type in HSIL-positive women living with HIV, was rarely detected as a single-type infection in HSIL and cancer cases.ConclusionHPV16, 18, and 45 should receive special attention for molecular diagnostic algorithms during CC prevention programs for HIV+ women from sub-Saharan Africa. HPV35 may have a high potential to induce HSIL in women living with HIV, but less potential to cause cervical cancer in single-type infections.

BackgroundCervical cancer - caused by persistent High Risk Human Papilloma Virus (HR HPV) infections - is the second most common cancer affecting women globally. HIV infection increases the risk for HPV persistence, associated disease progression and malignant cell transformation. We therefore hypothesized that this risk increase is directly linked to HIV infection associated dysfunction or depletion of HPV-oncoprotein-specific T-cell responses.MethodsThe 2H study specifically included HIV+ and HIV- women with and without cervical lesions and cancer to analyze HPV oncogene-specific T cell responses in relation to HPV infection, cervical lesion status and HIV status. Oncoprotein E6 and E7 specific T-cell responses were quantified for the most relevant types HPV16, 18 and 45 and control antigens (CMV-pp65) and M.tb-PPD in 373 women, using fresh peripheral blood mononuclear cells in an IFN-γ release ELISpot assay.ResultsOverall, systemic E6- and E7-oncoprotein-specific T-cell responses were infrequent and of low magnitude, when compared to CMV-pp65 and M.tb-PPD (p < 0.001 for all HR HPV types). Within HIV negative women infected with either HPV16, 18 or 45, HPV16 infected women had lowest frequency of autologous-type-E6/E7-specific T-cell responses (33%, 16/49), as compared to HPV18 (46% (6/13), p = 0.516) and HPV45 (69% (9/13), p = 0.026) infected women. Prevalent HPV18 and 45, but not HPV16 infections were linked to detectable oncoprotein-specific T-cell responses, and for these infections, HIV infection significantly diminished T-cell responses targeting the autologous infecting genotype. Within women living with HIV, low CD4 T-cell counts, detectable HIV viremia as well as cancerous and precancerous lesions were significantly associated with depletion of HPV oncoprotein-specific T-cell responses.DiscussionDepletion of HPV-oncoprotein-specific T-cell responses likely contributes to the increased risk for HR HPV persistence and associated cancerogenesis in women living with HIV. The low inherent immunogenicity of HPV16 oncoproteins may contribute to the exceptional potential for cancerogenesis associated with HPV16 infections.

Background Sexual and reproductive health (SRH) among young adults in developing countries is still a major public health concern. Early school-based sexuality education programs and sexual health information sharing between teachers, parents and young people have been considered protective against sexual health risks that young people are prone to. There is limited information on preferred choices of “ where ” and “ how ” young people like to get their SRH information. Here, we describe what young people prefer to learn with regard to sexual matters, where and who they prefer to learn from, and their experiences of parent-child sexuality communication. Methods This was a cross-sectional study, conducted from March 2019 to January 2020 among students aged 18-24 years attending Higher Learning Institutions (HLIs) within Mbeya. A self-administered questionnaire was used to collect information on SRH education, ability to discuss sexual matters with a parent/guardian, and SRH information gap during early sexual experience. Results Out of 504 students that were enrolled, 377 (74.8%) reported to be sexually active with mean age at sexual debut of 18.4 years. Six out of ten students found it difficult to discuss or did not discuss sexual matters with a parent/guardian while growing up at age 12-18 years. Majority learnt about SRH matters from peers (30%) and lessons at schools (23%). We found a gender-biased preference on sexual matters discussions, such that female and male participants preferred discussions with female adults and male adults, respectively. Peers (18%), Media (17%) and schools (13%) were preferred sources of SRH information. On recalling first sexual experience, participants felt they needed to know more about sexual feelings, emotions and relationships (26.9%), safer sex (13.8%), how to be able to say 'No' (10.5%) and how to use a condom correctly (10.2%). Conclusion Young people have a gender-biased preference when it comes to learning about SRH matters from their parents; however, such conversations seldom occur. Community health IEC should incorporate the agenda on building skills of parents on parent-child communication on sexual matters so as to empower them to confidently initiate and convey appropriate and sufficient sexual health information. Comprehensive SRH education and skills building is needed in the current school SRH curriculum in order need to meet the demand and needs of students’ and teachers’.

BACKGROUND:The burden of HPV-associated premalignant and malignant cervical lesions remains high in HIV+ women even under ART treatment. In order to identify possible underlying pathophysiologic mechanisms, we studied activation and HIV co-receptor expression in cervical T-cell populations in relation to HIV, HPV and cervical lesion status.METHODS:Cervical cytobrush (n = 468: 253 HIV- and 215 HIV+; 71% on ART) and blood (in a subset of 39 women) was collected from women in Mbeya, Tanzania. Clinical data on HIV and HPV infection, as well as ART status was collected. T cell populations were characterized using multiparametric flow cytometry-based on their expression of markers for cellular activation (HLA-DR), and memory (CD45RO), as well as HIV co-receptors (CCR5, α4β7).RESULTS:Cervical and blood T cells differed significantly, with higher frequencies of T cells expressing CD45RO, as well as the HIV co-receptors CCR5 and α4β7 in the cervical mucosa. The skewed CD4/CD8 T cell ratio in blood of HIV+ women was mirrored in the cervical mucosa and HPV co-infection was linked to lower levels of mucosal CD4 T cells in HIV+ women (%median: 22 vs 32; p = 0.04). In addition, HIV and HPV infection, and especially HPV-associated cervical lesions were linked to significantly higher frequencies of HLA-DR+ CD4 and CD8 T cells (p-values < 0.05). Interestingly, HPV infection did not significantly alter frequencies of CCR5+ or α4β7+ CD4 T cells.CONCLUSION:The increased proportion of activated cervical T cells associated with HPV and HIV infection, as well as HPV-associated lesions, together with the HIV-induced depletion of cervical CD4 T cells, may increase the risk for HPV infection, associated premalignant lesions and cancer in HIV+ women. Further, high levels of activated CD4 T cells associated with HPV and HPV-associated lesions could contribute to a higher susceptibility to HIV in HPV infected women.

Data was collected from a cross-sectional designed study, conducted from March 2019 to January 2020 in Mbeya region, Tanzania among students attending Higher Learning Institutions (HLIs) in the region registered by the Tanzania Commission for Universities (TCU). Eligible participants included Tanzanian students enrolled in HLIs within Mbeya region in any year of study, aged 18-24 years of age and agreed to provide written informed consent prior to all study-related procedures. Participants were ineligible to take part if they were students attending short-term courses (< 6 months) or elective students. Each HLI in Mbeya region was invited to participate. A complete electronic list of all students registered, aged 18-24 years of age was obtained from the Academic Registrars' offices. Based on the varying number of students from each HLI, and the study desired sample size, probability proportional to size was used to determine the total number of students by gender from each HLI. Students were not selected based on the department or course they are registered for. Each selected student was notified via phone that he/she has been randomly selected to take part in the study and if he/she was willing to take part, he/she was then requested to report to the data collection point within their respective campuses. An individual self-administered questionnaire was used in the study. The questionnaire was administered using a tablet or smart phone through a web-based software (ODK) or hard copy, which ever method the participant preferred. Data was entered in a database, and thereafter cleaned and analysed using statistical software Stata version 14 for Windows. Ethical approval was granted by the Mbeya Medical Research and Ethics Review Committee (MMREC) Reference Number SZEC-2439/R.A/V.1/07, Kilimanjaro Christian Medical College Research Ethics and Review Committee (CRERC) Reference Number 2405, and National Health Research Ethics Committee (NatHREC) Reference Number NIMR/HQ/R.8a/Vol.IX/3092. All eligible participants who agree to participate in this study received study information and were consented prior to any study related activity. Only participant’s study identification number was used in the questionnaire.