The origins of a research community in the Majengo observational cohort study, Nairobi, Kenya

<p>Abstract</p> <p>Background</p> <p>Since the 1980s the Majengo Observational Cohort Study (MOCS) has examined sexually transmitted infections, in particular HIV/AIDS, in a cohort of sex workers in Majengo, an impoverished urban village in Nairobi, Kenya. The MOCS investigators have faced criticism since the women have remained in the sex trade for the duration of their participation in the study, prompting concerns about exploitation. Yet despite these concerns, the cohort has survived for almost 30 years.</p> <p>Methods</p> <p>In this retrospective qualitative case study, we examine the community engagement practices of the MOCS and explore the factors that account for its durability.</p> <p>Results</p> <p>Women in sex work in Kenya were a highly stigmatized and disfranchised community. As a result, there was no natural 'community' of sex workers either in Nairobi or in the Majengo village. The Majengo clinic aimed to reduce the barriers to health care the women experienced at the STC clinic by bringing the services closer to them and by providing a non-discriminatory environment. The women acknowledged the fact they had hoped their participation in the MOCS would have helped them find a path out of the sex trade. But our findings also add another dimension to this debate, since every cohort member we interviewed expressed her gratitude for the deep impact the MOCS has had on her life, much of it beyond the improved health status made possible by access to quality healthcare services. Participation in the MOCS has improved and enriched their lives. The CE activities have played a central role in creating a community that did not exist independently of the MOCS.</p> <p>Conclusions</p> <p>Our case study identified 3 distinct phases of community engagement in the MOCS: (1) reaching out: mobilization, dialogue and education; (2) foundations of trust through relationships of care; and (3) leveraging existing social capital to form a cohort community. The findings demonstrate the importance of some of the less obvious benefits of participation in research, namely the evolving experience of community and the accompanying gains in personal security and solidarity that have kept the women in the cohort, some for 20 years or more.</p

Femtosecond laser-assisted selective holding with ultra-low power for direct manipulation of biological specimens

Traditional optical tweezers techniques often rely on high-power continuous wave (CW) lasers, which can introduce unwanted thermal effects and photodamage to delicate samples. To overcome these limitations, we demonstrate femtosecond laser assisted selective holding with ultra-low power (FLASH-UP). We find that the FLASH-UP exhibits a five times greater trap stiffness than CW-OT, and can trap at lower intensities. Furthermore, we demonstrate OT of different pathogenic bacteria species and find that FLASH-UP does not impact cell motility. These results pave the way for applications in sorting, bio-sensing, in vivo cell manipulation and single cell analysis

Evaluation of a Quantitative Real-Time PCR Assay to Measure HIV-Specific Mucosal CD8+ T Cell Responses in the Cervix

Several candidate HIV vaccines aim to induce virus-specific cellular immunity particularly in the genital tract, typically the initial site of HIV acquisition. However, standardized and sensitive methods for evaluating HIV-specific immune responses at the genital level are lacking. Therefore we evaluated real-time quantitative PCR (qPCR) as a potential platform to measure these responses. β-Actin and GAPDH were identified as the most stable housekeeping reference genes in peripheral blood mononuclear cells (PBMCs) and cervical mononuclear cells (CMCs) respectively and were used for normalizing transcript mRNA expression. HIV-specific cellular T cell immune responses to a pool of optimized CD8+ HIV epitopes (HIV epitope pool) and Staphylococcal enterotoxin B (SEB) superantigen control were assayed in HIV infected PBMC by qPCR, with parallel assessment of cytokine protein production. Peak HIV-specific mRNA expression of IFNγ, IL-2 and TNFα occurred after 3, 5 and 12 hours respectively. PBMCs were titrated to cervical appropriate cell numbers to determine minimum required assay input cell numbers; qPCR retained sensitivity with input of at least 2.5×104 PBMCs. This optimized qPCR assay was then used to assess HIV-specific cellular T cell responses in cytobrush-derived cervical T cells from HIV positive individuals. SEB induced IFNγ mRNA transcription was detected in CMCs and correlated positively with IFNγ protein production. However, qPCR was unable to detect HIV-induced cytokine mRNA production in the cervix of HIV-infected women despite robust detection of gene induction in PBMCs. In conclusion, although qPCR can be used to measure ex vivo cellular immune responses to HIV in blood, HIV-specific responses in the cervix may fall below the threshold of qPCR detection. Nonetheless, this platform may have a potential role in measuring mitogen-induced immune responses in the genital tract

Online socializing among men who have sex with men and transgender people in Nairobi and Johannesburg and implications for public health-related research and health promotion: an analysis of qualitative and respondent-driven sampling survey data.

INTRODUCTION: There is little published literature about gay, bisexual and other men who have sex with men and transgender individuals (MSM and TG)'s use of social media in sub-Saharan Africa, despite repressive social and/or criminalizing contexts that limit access to physical HIV prevention. We sought to describe MSM and TG's online socializing in Nairobi and Johannesburg, identifying the characteristics of those socializing online and those not, in order to inform the development of research and health promotion in online environments. METHODS: Respondent-driven sampling surveys were conducted in 2017 in Nairobi (n = 618) and Johannesburg (n = 301) with those reporting current male gender identity or male sex assigned at birth and sex with a man in the last 12 months. Online socializing patterns, sociodemographic, sexual behaviour and HIV-testing data were collected. We examined associations between social media use and sociodemographic characteristics and sexual behaviours among all, and only those HIV-uninfected, using logistic regression. Analyses were RDS-II weighted. Thirty qualitative interviews were conducted with MSM and TG in each city, which examined the broader context of and motivations for social media use. RESULTS: Most MSM and TG had used social media to socialize with MSM in the last month (60% Johannesburg, 71% Nairobi), mostly using generic platforms (e.g. Facebook), but also gay-specific (e.g. Grindr). HIV-uninfected MSM and TG reporting riskier recent sexual behaviours had raised odds of social media use in Nairobi, including receptive anal intercourse (adjusted OR = 2.15, p = 0.006), buying (aOR = 2.24, p = 0.015) and selling sex with men (aOR = 2.17, p = 0.004). Evidence for these associations was weaker in Johannesburg, though socializing online was associated with condomless anal intercourse (aOR = 3.67, p = 0.003) and active syphilis (aOR = 13.50, p = 0.016). Qualitative findings indicated that while online socializing can limit risk of harm inherent in face-to-face interactions, novel challenges were introduced, including context collapse and a fear of blackmail. CONCLUSIONS: Most MSM and TG in these cities socialize online regularly. Users reported HIV acquisition risk behaviours, yet this space is not fully utilized for sexual health promotion and research engagement. Effective, safe and acceptable means of using online channels to engage with MSM/TG that account for MSM and TG's strategies and concerns for managing online security should now be explored, as complements or alternatives to existing outreach

Presence of CD8+ T Cells in the Ectocervical Mucosa Correlates with Genital Viral Shedding in HIV-Infected Women despite a Low Prevalence of HIV RNA–Expressing Cells in the Tissue

The female genital tract is a portal of entry for sexual HIV transmission and a possible viral reservoir. In this study, the ectocervical CD8+ T cell distribution was explored in situ and was related to expression of CD3 and HLA-DR and presence of HIV RNA. For this purpose, ectocervical tissue samples and genital secretions were collected from HIV-seropositive (HIV+) Kenyan female sex workers (FSWs) (n = 20), HIV-seronegative (HIV−) FSWs (n = 17), and HIV− lower-risk women (n = 21). Cell markers were assessed by in situ staining and by quantitative PCR. HIV RNA expression in tissue was analyzed by in situ hybridization, and viral shedding was assessed by quantitative PCR. The HIV+FSW group had a higher amount of total cells and CD8+, CD3+, and HLA-DR+ cells compared with the HIV−FSW group and HIV− lower-risk women. The majority of CD8+ cells were CD3+ T cells, and the numbers of CD8+ cells correlated significantly with plasma and cervical viral load. HIV RNA expression in situ was found in 4 of the 20 HIV+FSW women but did not correlate with cervical or plasma viral load. Thus, the HIV+ women displayed high numbers of CD8+, CD3+, and HLA-DR+ cells, as well as a limited number of HIV RNA+ cells, in their ectocervical mucosa; hence, this localization cannot be neglected as a potential viral reservoir. The elevated levels of CD8+ T cells may play a role in the immunopathogenesis of HIV in the female genital tract

Presence of CD8+ T Cells in the Ectocervical Mucosa Correlates with Genital Viral Shedding in HIV-Infected Women despite a Low Prevalence of HIV RNA–Expressing Cells in the Tissue

The female genital tract is a portal of entry for sexual HIV transmission and a possible viral reservoir. In this study, the ectocervical CD8+ T cell distribution was explored in situ and was related to expression of CD3 and HLA-DR and presence of HIV RNA. For this purpose, ectocervical tissue samples and genital secretions were collected from HIV-seropositive (HIV+) Kenyan female sex workers (FSWs) (n = 20), HIV-seronegative (HIV−) FSWs (n = 17), and HIV− lower-risk women (n = 21). Cell markers were assessed by in situ staining and by quantitative PCR. HIV RNA expression in tissue was analyzed by in situ hybridization, and viral shedding was assessed by quantitative PCR. The HIV+FSW group had a higher amount of total cells and CD8+, CD3+, and HLA-DR+ cells compared with the HIV−FSW group and HIV− lower-risk women. The majority of CD8+ cells were CD3+ T cells, and the numbers of CD8+ cells correlated significantly with plasma and cervical viral load. HIV RNA expression in situ was found in 4 of the 20 HIV+FSW women but did not correlate with cervical or plasma viral load. Thus, the HIV+ women displayed high numbers of CD8+, CD3+, and HLA-DR+ cells, as well as a limited number of HIV RNA+ cells, in their ectocervical mucosa; hence, this localization cannot be neglected as a potential viral reservoir. The elevated levels of CD8+ T cells may play a role in the immunopathogenesis of HIV in the female genital tract

HIV burden and correlates of infection among transfeminine people and cisgender men who have sex with men in Nairobi, Kenya: an observational study.

BACKGROUND: Transgender people are disproportionately affected by HIV and other sexually transmitted infections (STIs) worldwide, and culturally competent prevention and treatment services are often unavailable or inaccessible. Despite recent improvements in national HIV responses for many key populations in east Africa, evidence of effective responses informed by transgender sexual health needs is sparse. We aimed to assess gender identity among men and transgender people who have sex with men in Kenya, and to explore its associations with sexual health-related outcomes, risk behaviours, and uptake of HIV prevention and care interventions. METHODS: We did a cross-sectional study in Nairobi, Kenya, and recruited adult cisgender men and transfeminine people who reported having sex with men, through respondent-driven sampling. Inclusion criteria were possession of a valid study coupon, being aged 18 years or older, having male sex assignment at birth or male gender identification currently, living within 50 km of Nairobi, and having had consensual anal or oral sexual activity with a man in the previous 12 months. Seed participants were identified by three community organisations that provide targeted health-care services to gay, bisexual, or other men who have sex with men (MSM) communities in Nairobi. We assessed gender identity, sociodemographics, sexual behaviour, and HIV prevention and care uptake, by self-completed survey. Participants were tested for HIV, syphilis, and rectal and urethral gonorrhoea and chlamydia. We compared prevalence of sexual health outcomes, risk behaviour, and HIV prevention and care service uptake among transfeminine and cisgender participants, using multivariable robust Poisson regression models, with gender identity as the independent variable. FINDINGS: Between May 4 and Dec 8, 2017, we enrolled 618 participants. Six participants did not answer the questions on sex assigned at birth and gender identity and so were excluded from the analyses. 522 (sample-weighted percentage 86%) of 612 participants were classified as cisgender men, 70 (11%) as transfeminine, and three (<1%) as transmasculine. 17 participants (2%) did not identify as male, female, or transgender. Compared with cisgender men, transfeminine people were more likely to be HIV-positive (28 [41%] of 70 transfeminine vs 151 [25%] of 521 cisgender men; p=0·0009) and to report current symptoms consistent with a rectal STI (eight [16%] of 67 vs 38 [7%] of 518; p=0·014). Transfeminine people reported higher numbers of recent male sexual partners (22 [27%] of 70 transfeminine people reported four or more male sexual partners in the past 3 months vs 112 [13%] of 522 cisgender men; p=0·042) and were more likely to report condomless anal intercourse with men (43 [62%] of 70 vs 208 [39%] of 522; p=0·0009) and receptive anal intercourse (54 [76%] of 70 vs 252 [46%] of 522; p<0·0001) in the past 3 months, and transactional sex with men (42 [57%] of 69 vs 240 [42%] of 518; p=0·023) and experience of sexual assault (16 [23%] of 69 vs 65 [11%] of 520; p=0·019) in the past 12 months. Use of pre-exposure prophylaxis and post-exposure prophylaxis was low in both groups. INTERPRETATION: Transfeminine people who have sex with men have a higher burden of HIV and associated risk behaviours compared with cisgender MSM in the same context, yet their uptake of prevention and care services is poor. Policies should acknowledge the specific needs of transfeminine people as distinct from cisgender MSM, and support health-care providers to address these needs. FUNDING: Evidence for HIV Prevention in Southern Africa (EHPSA), UK Aid

The Role of Chlamydia trachomatis in High-Risk Human Papillomavirus Persistence Among Female Sex Workers in Nairobi, Kenya

Little is known about risk factors for persistent high-risk HPV (hrHPV) infection in low-income settings, and prior research has not quantified the relative duration of hrHPV infections stratified by risk factors. We compared the duration of hrHPV infection among female sex workers (FSW) by exposure to sexually transmitted infections (STIs), using a highly-sensitive biomarker assay

HIV-1 Clade D Is Associated with Increased Rates of CD4 Decline in a Kenyan Cohort

HIV-1 is grouped phylogenetically into clades, which may impact rates of HIV-1 disease progression. Clade D infection in particular has been shown to be more pathogenic. Here we confirm in a Nairobi-based prospective female sex worker cohort (1985-2004) that Clade D (n = 54) is associated with a more rapid CD4 decline than clade A1 (n = 150, 20.6% vs 13.4% decline per year, 1.53-fold increase, p = 0.015). This was independent of "protective" HLA and country of origin (p = 0.053), which in turn were also independent predictors of the rate of CD4 decline (p = 0.026 and 0.005, respectively). These data confirm that clade D is more pathogenic than clade A1. The precise reason for this difference is currently unclear, and requires further study. This is first study to demonstrate difference in HIV-1 disease progression between clades while controlling for protective HLA alleles