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BackgroundEvidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) by risk groups is limited in Africa. We assessed prevalence, trends, and transmission dynamics of pre-treatment HIVDR within-and-between men who have sex with men (MSM), people who inject drugs (PWID), female sex workers (FSW), heterosexuals (HET), and children infected perinatally in Kenya.MethodsHIV-1 partialpolsequences from antiretroviral-naïve samples collected between 1986-2020 were used. Pre-treatment RTI, PI and INSTI mutations were assessed using the Stanford HIVDR database. Phylogenetics methods were used to determine and date transmission clusters.ResultsOf 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2-16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSW (15.1%) and HET (13.9%). No INSTI resistance mutations were detected. Among HET, pre-treatment HIVDR increased from 6.6% in 1986-2005 to 20.2% in 2011-2015 but dropped to 6.5% in 2016-2020. Overall, 22 clusters with shared pre-treatment HIVDR mutations were identified. The largest was a K103N mutation cluster involving 16 MSM sequences sampled between 2010-2017, with an estimated tMRCA of 2005 (HPD, 2000-2008). This lineage had a growth rate=0.1/year and R0=1.1, indicating propagation over 12 years among ART-naïve MSM in Kenya.ConclusionsCompared to HET, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2016 may have reversed the increase in pre-treatment RTI mutations in Kenya. Continued surveillance of HIVDR, with a particular focus on children and key populations, is warranted to inform treatment strategies in Kenya.SummaryCompared to the heterosexual population, key populations had higher levels of pre-treatment HIV-1 drug resistance (HIVDR). Propagation of HIVDR was risk-group exclusive. Introduction of integrase inhibitors abrogated propagation of reverse transcriptase inhibitors mutations among the heterosexual, but not key populations.

Objective To assess the feasibility of conducting HIV prevention trials among key populations in Nairobi, Kenya. Background HIV prevention trials require the inclusion of those at high risk of HIV infection and their informed decision to take part and remain in the clinical trial to the end is crucial. In Kenya key populations including men who have sex with men (MSM) and female sex workers (FSW) are, disproportionately, at high risk of HIV infection when compared to the general population. Few trials testing biomedical prevention products against HIV have enrolled Kenyan FSW and MSM. Methods We performed simulated vaccine efficacy trial (SiVET) using licensed hepatitis B vaccines as substitutes for a HIV vaccine candidate and included randomization for those immune to hep B. The SiVET was an observational study designed to mimic the rigors of a clinical trial; we assessed HIV risk, provided risk counselling and prevention tools and performed HIV testing at baseline and periodically until the end of the trial. MSM and FSW were enrolled at a ratio of 4:1. Volunteers were assigned to either hepatitis B vaccine or placebo. Results Recruitment took approximately 24 months between Sep 2015 and Sep 2017. Of the 368 volunteers screened, 250 (200 MSM and 50 FSW) were enrolled. Reasons for exclusion at screening included: being positive for HIV (n = 7), hepatitis (n = 14), other pre-existing medical conditions (n = 41), eligible but chose not to enrol (n = 47). Most of the volunteers adhered to study procedures and attended their study visits within the study window. These include volunteers who received the second vaccination 244 (98%), the third vaccination 228 (91%) and, the final study visit 217 (87%). The reasons volunteers discontinued from the study early included: relocation and loss to follow up (n = 14). A total of 8 cases of HIV infection were observed in 174.5 Person Years at Risk (PYAR), all among MSM, including 5 seroconversions identified at the last study visit, for a HIV incidence of 4.58 cases/ 100 PYAR, among MSM enrolled in the study. Conclusion Our findings suggest that it is possible to conduct HIV prevention trials among key populations in Nairobi with a good adherence to a vaccine efficacy trial schedule. Despite HIV prevention efforts, we also noted a high incidence of HIV infection. This demonstrates the need for effective HIV prevention products in these populations.

In Kenya, HIV-1 key populations including men having sex with men (MSM), people who inject drugs (PWID) and female sex workers (FSW) are thought to significantly contribute to HIV-1 transmission in the wider, mostly heterosexual (HET) HIV-1 transmission network. However, clear data on HIV-1 transmission dynamics within and between these groups are limited. We aimed to empirically quantify rates of HIV-1 flow between key populations and the HET population, as well as between different geographic regions to determine HIV-1 'hotspots' and their contribution to HIV-1 transmission in Kenya. We used maximum-likelihood phylogenetic and Bayesian inference to analyse 4058 HIV-1 pol sequences (representing 0.3 per cent of the epidemic in Kenya) sampled 1986-2019 from individuals of different risk groups and regions in Kenya. We found 89 per cent within-risk group transmission and 11 per cent mixing between risk groups, cyclic HIV-1 exchange between adjoining geographic provinces and strong evidence of HIV-1 dissemination from (i) West-to-East (i.e. higher-to-lower HIV-1 prevalence regions), and (ii) heterosexual-to-key populations. Low HIV-1 prevalence regions and key populations are sinks rather than major sources of HIV-1 transmission in Kenya. Targeting key populations in Kenya needs to occur concurrently with strengthening interventions in the general epidemic. ispartof: VIRUS EVOLUTION vol:8 issue:1 ispartof: location:England status: published

Sub-Saharan Africa carries the biggest burden of the human immunodeficiency virus type 1 (HIV-1)/AIDS epidemic and is in an urgent need of an effective vaccine. CD8+ T cells are an important component of the host immune response to HIV-1 and may need to be harnessed if a vaccine is to be effective. CD8+ T cells recognize human leukocyte antigen (HLA)-associated viral epitopes and the HLA alleles vary significantly among different ethnic groups. It follows that definition of HIV-1-derived peptides recognized by CD8+ T cells in the geographically relevant regions will critically guide vaccine development. Here, we study fine details of CD8+ T-cell responses elicited in HIV-1/2-uninfected individuals in Nairobi, Kenya, who received a candidate vaccine delivering conserved regions of HIV-1 proteins called HIVconsv. Using 10-day cell lines established by in vitro peptide restimulation of cryopreserved PBMC and stably HLA-transfected 721.221/C1R cell lines, we confirm experimentally many already defined epitopes, for a number of epitopes we define the restricting HLA molecule(s) and describe four novel HLA-epitope pairs. We also identify specific dominance patterns, a promiscuous T-cell epitope and a rescue of suboptimal T-cell epitope induction in vivo by its functional variant, which all together inform vaccine design.

Sub-Saharan Africa carries the biggest burden of the human immunodeficiency virus type 1 (HIV-1)/AIDS epidemic and is in an urgent need of an effective vaccine. CD8+ T cells are an important component of the host immune response to HIV-1 and may need to be harnessed if a vaccine is to be effective. CD8+ T cells recognize human leukocyte antigen (HLA)-associated viral epitopes and the HLA alleles vary significantly among different ethnic groups. It follows that definition of HIV-1-derived peptides recognized by CD8+ T cells in the geographically relevant regions will critically guide vaccine development. Here, we study fine details of CD8+ T-cell responses elicited in HIV-1/2-uninfected individuals in Nairobi, Kenya, who received a candidate vaccine delivering conserved regions of HIV-1 proteins called HIVconsv. Using 10-day cell lines established by in vitro peptide restimulation of cryopreserved PBMC and stably HLA-transfected 721.221/C1R cell lines, we confirm experimentally many already defined epitopes, for a number of epitopes we define the restricting HLA molecule(s) and describe four novel HLA-epitope pairs. We also identify specific dominance patterns, a promiscuous T-cell epitope and a rescue of suboptimal T-cell epitope induction in vivo by its functional variant, which all together inform vaccine design.

ObjectiveTo evaluate factors associated with willingness to participate in future HIV vaccine trials among men who have sex with men and female sex workers living in Nairobi, Kenya.BackgroundWorking with 'key populations', those at elevated risk of HIV acquisition, is important to conduct efficient HIV prevention trials. In Nairobi Kenya, HIV infection is higher in men who have sex with men (MSM) and female sex workers (FSW) than in the general adult population, hence the need to establish if they would be willing to participate in future HIV vaccine trials.MethodsWe administered a structured questionnaire to MSM and FSW enrolled in a simulated vaccine efficacy trial (SiVET). The SiVET was an observational study designed to mimic the rigors of a clinical trial to assess HIV risk characteristics at baseline. After 12-15 months of follow-up, a structured questionnaire was administered to evaluate hypothetical willingness to participate in future HIV vaccine trials.ResultsOf 250 persons (80% MSM by design) enrolled in SiVET, 214 attended the final study visit and 174 (81%) of them expressed hypothetical willingness to participate in future HIV vaccine trials. These were 82% of MSM and 80% of FSW of those who attended the final study visit. Having a very good experience in the SiVET trial predicted willingness to participate in future HIV vaccine trials. Motivating factors for participation included a desire to receive education about HIV (59%) and to receive healthcare (57%).ConclusionsOur data demonstrate high willingness among key populations in Kenya, to participate in future HIV vaccine trials after completing participation in a SiVET. The findings suggest that these groups might be a reliable target population for consideration in future HIV vaccine trials. Assessment of willingness to participate in these populations provides important information that may help to inform future education and recruitment efforts for vaccine trials. Improving the research experience for members of key populations could impact their willingness to participate in HIV vaccine trials.

We show that VZV-seropositive women sustain VZV-specific humoral immunity at the gastrointestinal and genital mucosa and that this immunity can be boosted upon vaccination. Our findings encourage further investigation of VZV as a potential vector in vaccines including HIV., Background Attenuated varicella zoster virus (VZV) is a promising vector for recombinant vaccines. Because human immunodeficiencyvirus (HIV) vaccines are believed to require mucosal immunogenicity, we characterized mucosal VZV-specific humoral immunity following VZVOka vaccination. Methods Adult Kenyan VZV-seropositive women (n = 44) received a single dose of the live zoster VZVOka vaccine. The anamnestic responses to the virus were followed longitudinally in both plasma and mucosal secretions using an in-house glycoprotein enzyme-linked immunosorbent assay and safety and reactogenicity monitored. VZV seroprevalence and baseline responses to the virus were also characterized in our cohorts (n = 288). Results Besides boosting anti-VZV antibody responses systemically, vaccination also boosted anti-VZV immunity in the cervicovaginal mucosa with a 2.9-fold rise in immunoglobulin G (P < .0001) and 1.6-fold rise in immunoglobulin A (IgA) (P = .004) from the time before immunization and 4 weeks postvaccination. Baseline analysis demonstrated high avidity antibodies at the gastrointestinal and genital mucosa of VZV-seropositive women. Measurement of VZV-specific IgA in saliva is a sensitive tool for detecting prior VZV infection. Conclusions VZVOka vaccine was safe and immunogenic in VZV-seropositive adult Kenyan women. We provided compelling evidence of VZV ability to induce genital mucosa immunity. Clinical Trials Registration NCT02514018.

Background During the 2014 West African Ebola outbreak, Ebola vaccine development was accelerated. The phase 1 VAC52150EBL1003 study was performed to investigate 2-dose heterologous vaccination with Ad26.ZEBOV and MVA-BN-Filo in an African population located in a high-altitude setting in Nairobi, Kenya. Methods Healthy adult volunteers were randomized to receive one of four 2-dose vaccination schedules. The first vaccination was administered at baseline (Ad26.ZEBOV or MVA-BN-Filo), followed by the second vaccination with the alternate vaccine after either 28 or 56 days. Each schedule had a placebo comparator group. The primary objective was to assess the safety and tolerability of these regimens. Results Seventy-two volunteers were randomized into 4 groups of 18 (15 received vaccine, and 3 received placebo). The most frequent solicited systemic adverse event was headache (frequency, 50%, 61%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively). The most frequent solicited local AE was injection site pain (frequency, 78%, 63%, and 33% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively). No differences in adverse events were observed among the different vaccine regimens. High levels of binding and neutralizing anti–Ebola virus glycoprotein antibodies were induced by all regimens and sustained to day 360 after the first dose. Conclusions Two-dose heterologous vaccination with Ad26.ZEBOV and MVA-BN-Filo was well tolerated and highly immunogenic against Ebola virus glycoprotein. Clinical trials registration NCT02376426, This phase 1 study demonstrated that 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo vaccines was well tolerated and induced durable immune responses to Ebola virus in healthy African volunteers for up to 360 days after the priming dose.

IntroductionIntramuscular electroporation (IM/EP) is a vaccine delivery technique that improves the immunogenicity of DNA vaccines. We evaluated the acceptability and tolerability of electroporation among healthy African study participants.MethodsForty-five participants were administered a DNA vaccine (HIV-MAG) or placebo by electroporation at three visits occurring at four week-intervals. At the end of each visit, participants were asked to rate pain at four times: (1) when the device was placed on the skin and vaccine injected, before the electrical stimulation, (2) at the time of electrical stimulation and muscle contraction, and (3) at 10 minutes and (4) 30 minutes after the procedure was completed. For analyses, pain level was dichotomized as either "acceptable" (none/slight/uncomfortable) or "too much" (Intense, severe, and very severe) and examined over time using repeated measures models. Optional brief comments made by participants were summarized anecdotally.ResultsAll 45 participants completed all three vaccination visits; none withdrew from the study due to the electroporation procedure. Most (76%) reported pain levels as acceptable at every time point across all vaccination visits. The majority of "unacceptable" pain was reported at the time of electrical stimulation. The majority of the participants (97%) commented that they preferred electroporation to standard injection.ConclusionRepeated intramuscular electroporation for vaccine delivery was found to be acceptable and feasible among healthy African HIV vaccine trial participants. The majority of participants reported an acceptable pain level at all vaccination time points. Further investigation may be warranted into the value of EP to improve immunization outcomes. ClinicalTrials.gov NCT01496989.

BackgroundThe Globally Relevant AIDS Vaccine Europe-Africa Trials (GREAT) partnership is an EDCTP-funded project that aims to foster collaboration between institutions in Europe and sub-Saharan Africa to build capacity among African clinical research centres (CRCs) for the design and conduct of HIV-1 vaccine efficacy trials.MethodsIn January 2017, the University of Oxford (UOXF) and five CRCs in Kenya, Uganda and Zambia were awarded a 5 year grant for capacity building and to support conduct of an HIV-1 vaccine trial in different high-risk populations across Africa using cross-clade (conserved protein regions) T-cell vaccines. UOXF and CRCs embarked on activities to strengthen capacity of the CRCs for future efficacy trials. This included training, community engagement, cohort preparation and infrastructure upgrade.ResultsIn the first year, the African investigators at the CRCs collaborated on the development of a protocol aimed at assessing the safety and immunogenicity of the tHIVconsvX vaccines. In preparation for the planned vaccine trial, infrastructure upgrades were prioritised at all partner sites and this included building laboratory space and procurement of appropriate laboratory equipment. Planned infrastructure upgrades will also ensure that high-risk populations can be safely and confidentially included in HIV prevention clinical trials. Systematic community engagement was implemented at all sites, training in GCP/GCLP was provided and training is planned for nominated CRC staff to lead community engagement efforts.ConclusionImproved infrastructure and the provision of targeted training will enhance future trials and increase the capacities of CRCs and staff to conduct quality trials in previously hard-to-reach populations. Early collaboration between investigators from European and sub-Saharan African institutions, with equal responsibilities in the protocol development process, established a meaningful partnership. EDCTP funding also offers a unique opportunity for capacity building.

Table of contents A1 Introduction to the 2nd synchronicity forum of GHRI/CHVI-funded Canadian and African HIV prevention and vaccine teams O1 Voluntary medical male circumcision for prevention of heterosexual transmission of HIV in adult males in Soweto: What do indicators and incidence rate show? Hillary Mukudu, Neil Martinson, Benn Sartorius O2 Developing a peer-led community mobilization program for sex workers in Soweto: HIV risk and demographics Jenny Coetzee, Janan Dietrich, Kgaugelo Mokgatswana, Rachel Jewkes, Glenda E. Gray O3 Salient beliefs about adherence: A qualitative survey conducted as part of the demonstration study on "treatment as prevention" (TasP) and "pre-exposure prophylaxis" (PrEP) among female sex workers (FSWS) in Cotonou, Benin Marylène Dugas, Luc Béhanzin, Fernand A. Guédou, Marie-Pierre Gagnon, Michel Alary O4 Relative perception of risk as a driver of unsafe sexual practices among key populations: Cases of fisherfolk and women and their partners involved in multiple sexual partnerships in Uganda Rwamahe Rutakumwa, Martin Mbonye, Thadeus Kiwanuka, Sarah Nakamanya, Richard Muhumuza, Winfred Nalukenge, Janet Seeley O5 Exploring the acceptability of new biomedical HIV prevention technologies among MSM, adolescents and heterosexual adults in South Africa Millicent Atujuna, Melissa Wallace, Ben Brown, Linda Gail Bekker, Peter A. Newman O6 HIV-susceptible target cells in foreskins after voluntary medical male circumcision in South Africa Rushil Harryparsad, Abraham J. Olivier, Heather B. Jaspan, Douglas Wilson, Janan Dietrich, Neil Martinson, Hillary Mukudu, Nonhlanhla Mkhize, Lynn Morris, Gianguido Cianci, Minh Dinh, Thomas Hope, Jo-Ann S. Passmore, Clive M. Gray O7 HIV-1 proteins activate innate immune responses via TLR2 heterodimers Bethany M. Henrick, Xiao-Dan Yao, Kenneth L. Rosenthal, the INFANT Study Team O8 Characterization of an innate factor in human milk and mechanisms of action against HIV-1 Bethany M. Henrick, Xiao-Dan Yao, Anna G. Drannik, Alash’le Abimiku, Kenneth L. Rosenthal, the INFANT Study Team O9 Secretor status and susceptibility to HIV infections among female sex workers in Nairobi, Kenya Nadia Chanzu, Walter Mwanda, Julius Oyugi, Omu Anzala O10 Natural Killer cell recall responsiveness to Gag-HIV-1 peptides of HIV-1 exposed but uninfected subjects are associated with peripheral CXCR6+ NK cell subsets Moustapha Mbow, Sabelle Jallow, Moussa Thiam, Alberta Davis, Assane Diouf, Cheikh T. Ndour, Moussa Seydi, Tandakha N. Dieye, Souleymane Mboup, Martin Goodier, Eleanor Rilley, Assan Jaye O11 Profiles of resistance: Local innate mucosal immunity to HIV-1 in commercial sex workers Xiao-Dan Yao, RW. Omange, Bethany M. Henrick, Richard T. Lester, Joshua Kimani, T. Blake Ball, Francis A. Plummer, Kenneth L. Rosenthal O12 Early antiretroviral therapy and pre-exposure prophylaxis for HIV prevention among female sex workers in Cotonou, Benin: A demonstration project Luc Béhanzin, Fernand A. Guédou, Nassirou Geraldo, Ella Goma Mastétsé, Jerôme Charles Sossa, Marcel Djimon Zannou, Michel Alary O13 Building capacity for HIV prevention trials: Preliminary data from a Nigerian cohort of HIV exposed sero-negatives (HESN) Sophia Osawe, Evaezi Okpokoro, Felicia Okolo, Stephen Umaru, Rebecca Abimiku, Sam Audu, Pam Datong, Alash’le Abimiku O14 Equipping healthcare professionals with skills required for the conduct of clinical trials in an effort to build capacity. Lessons learned Jacquelyn Nyange, Joyce Olenja, Gaudensia Mutua, Walter Jaoko, Gloria Omosa-Manyonyi, Bashir Farah, Maureen Khaniri, Omu Anzala O15 Educational technology to support active learning for HIV researchers and planners Anne Cockcroft, Kendra Tonkin, Indu Girish, Puna Mhati, Ashley Cunningham, Neil Andersson O16 From Lake Kivu (Rwanda) and Lake Malawi (Tanzania) to the shores of Lake Victoria (Uganda): Strengthening laboratory capacity through Good Clinical Laboratory Practice training Bashir Farah, Jackton Indangasi, Walter Jaoko, Gaudensia Mutua, Maureen Khaniri, Jacquelyn Nyange, Omu Anzala O17 Rilpivirine and etravirine resistance mutations in HIV-1 subtype C infected patients on a non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy in Botswana Thabo Diphoko, Simani Gaseitsiwe, Victoria Maiswe, Thato Iketleng, Dorcas Maruapula, Keabetswe Bedi, Sikhulile Moyo, Rosemary Musonda, Mark Wainberg, Joseph Makhema, Vladimir Novitsky, Richard Marlink, Max Essex O18 From home-based HIV testing to initiation of treatment: The AIDS Support Organization (TASO) Experience with Home-based HIV Counselling and Testing (HBHCT) among Adolescents in Uganda, 2005-2011 Stephen Okoboi, Livingstone Ssali, Sam Kalibala, Josephine Birungi, Aggrey Egessa, Jonathan Wangisi, Lyavala Joanne Okullu, Celestin Bakanda, Francis Obare41 O19 Feasibility study on using real time medication monitoring among HIV infected and Tuberculosis patients in Kilimanjaro, Tanzania I. Marion Sumari-de Boer, Hadija H. Semvua, Jossy van den Boogaard, Krisanta W. Kiwango, Kennedy M. Ngowi, Pythia T. Nieuwkerk, Rob E. Aarnoutse, Ireen Kiwelu, Eva Muro, Gibson S. Kibiki O20 Deaths still among sero-discordant cohort in Nigeria despite Access to treatment Ruth Datiri, Grace Choji, Sophia Osawe, Evaezi Okpokoro, Felicia Okolo, Stephen Umaru, Rebecca Abimiku, Samuel Audu, Pam Datong, Alash’le Abimiku O21 Therapeutic HIV-1 vaccine trials in Denmark and Guinea-Bissau Fomsgaard A, Karlsson I, Jensen KJ, Jensen SS, Leo-Hansen C, Jespersen S, Da Silva Té D, Rodrigues CM, da Silva ZJ, Janitzek CM, Gerstoft J, Kronborg G, the WAPHIR Group O22 Willingness to participate in a HIV vaccine Trial among HIV exposed sero-negative (HESN) persons in Jos, Nigeria Evaezi Okpokoro, Sophia Osawe, Ruth Daitiri, Grace Choji, Stephen Umaru, Felicia Okolo, Pam Datong, Alash'le Abimiku O23 Clinical research volunteers’ perceptions and experiences of screening for enrolment at KAVI-Institute of Clinical Research, Kenya Nyariki Emily, Olenja Joyce, Lorway R. Robert, Anzala Anzala O24 Gut microbiome, HIV-exposure, and vaccine responses in South African infants Katie Viljoen, Jerome Wendoh, Elvis Kidzeru, Ulas Karaoz, Eoin Brodie, Gerrit Botha, Nicola Mulder, Clive Gray, William Cameron, Alain Stintzi, Heather Jaspan, for the INFANT study team O25 Analysis of HIV pol diversity in the concentrated HIV epidemic in Saskatchewan Paul N. Levett, David Alexander, Naveed Gulzar, Prabvir S. Grewal, Art F. Y. Poon, Zabrina Brumme, P. Richard Harrigan, James I. Brooks, Paul A. Sandstrom, Stryker Calvez, Stephen E. Sanche, Jamie K. Scott P1 Evaluating a HIV vaccine research community engagement programme at two HIV prevention research centres in the Western Cape Leslie Swartz, Ashraf Kagee, Anthea Lesch, Zuhayr Kafaar, Anneliese De Wet P2 Validating HIV acquisition risk score using a cohort HIV exposed sero-negative persons in a discordant relationship in Jos, Nigeria, West Africa Evaezi Okpokoro, Sophia Osawe, Ruth Daitiri, Grace Choji, Stephen Umaru, Felicia Okolo, Pam Datong, Alash'le Abimiku P3 Bridging the gap between adults and adolescents and youth adults (AYA) – Employing a youth-centred approach to investigate HIV risk among AYA in Soweto and Durban, South Africa Janan Dietrich, Tricia Smith, Laura Cotton, Stefanie Hornschuh, Martin van der Watt, Cari L. Miller, Glenda Gray, Jenni Smit, Manjeetha Jaggernath, Thumbi Ndung’u, Mark Brockman, Angela Kaida, on behalf of the AYAZAZI study teams P4 Neighbours to sex workers: A key population that has been ignored Maureen Akolo, Joshua Kimani, Prof Larry Gelmon, Michael Chitwa, Justus Osero P5 Young women’s access to structural support programmes in a district of Botswana Anne Cockcroft, Nobantu Marokoane, Leagajang Kgakole, Boikhutso Maswabi, Neo Mpofu, Umaira Ansari, Neil Andersson P6 Voices for action from peri-urban Ugandan students, teachers and parents on HIV/STI prevention: Qualitative research results Nakinobe Elizabeth, Miiro George Mukalazi, Zalwango Flavia, Nakiyingi-Miiro Jessica, Kaleebu Potiano P7 Engaging Social Media as an education tool on the fly: The use of Facebook for HIV and Ebola prevention and awareness amongst adolescents in Uganda John Ross Semwanga, Emily Nyanzi, Saidat Namuli Musoke, Elizabeth Nakinobe, George Miiro, Edward Katongole Mbidde, Tom Lutalo, Pontiano Kaleebu P8 Circulating HIV-1 subtypes among sexual minority populations in Zambia Ray Handema, Graham P. Chianzu P9 The Development of HIV Bio-bank resource management to support clinical trial and Intervention research: WAPHIR experience Moussa Thiam, Diabou Diagne-Gueye, Mame K. Ndiaye, Moustapha Mbow, Birahim P. Ndiaye, Ibrahima Traore, Mamadou C. Dia, Gilleh Thomas, Coumba Tour-Kane, Souleymane Mboup, Assan Jaye P10 Capacity building for clinical trials as a novel approach for scaling up HIV prevention research initiatives in East Africa: achievements and challenges Emily Nyanzi, Edward Katongole Mbidde, Pontiano Kaleebu, Juliet Mpendo, Joshua Kimani, Josephine Birungi, Winnie Muyindike, Andrew Kambugu P11 Community and media perspective of research; an advocacy workshop on HIV prevention research Hachizovu Sebastian, Handema Ray, Chaponda Mike, Kabuya Jean Bertin, Mulenga Modest P12 Development of a quantitative HIV-1 and HIV-2 real time PCR (qRT-PCR) viral load assay Moussa Thiam, Omar Janha, Alberta Davis, Alfred Amambua-Ngwa, Davis C. Nwakanma, Souleymane Mboup, Assan Jaye P13 Differential effects of sex in a West African Cohort of HIV-1, HIV-2 and HIV-1/2 dual infected patients: Men are worse off Sanne Jespersen, Bo Langhoff Hønge, Joakim Esbjörnsson, Candida Medina, David Da Silva TÉ, Faustino Gomes Correira, Alex Lund Laursen, Lars Østergaard, Andreas Andersen, Peter Aaby, Christian Erikstrup, Christian Wejse, for the Bissau HIV Cohort study group P14 HIV-infected adolescents in transition from pediatric to adult HIV care in Dakar, Senegal: sample characteristics and immunological and virological profiles Siry Dieye, Moussa Sarr, Haby Sy, Helene D Mbodj, Marianne Ndiaye, Amy Ndiaye, Seydi Moussa, Assan Jaye, Souleymane Mboup100 P15 Molecular characterization of vertically transmitted HIV-1 among children born to HIV-1 seropositive mothers in Northern Tanzania Balthazar M. Nyombi, Elichilia R. Shao, Innocent B. Chilumba, Sikhulile Moyo, Simani Gaseitsiwe, Rosemary Musonda P16 Breast-fed HIV-1 exposed infants play catch up. A preliminary report Pam Datong, Bucky Inyang, Sophia Osawe, Abel Izang, Chundung Cole, Felicia Okolo, Bill Cameron, Kenneth Rosenthal, Clive Gray, Heather Jaspan, Alash’le Abimiku, the INFANT study team P17 The frequency of N348I mutation in patient failing combination antiretroviral treatment In Botswana Boitumelo Seraise, Kerstin Andrea-Marobela, Sikhulile Moyo, Rosemary Musonda, Joseph Makhema, Max Essex, Simani Gaseitsiwe

Standards of care provided to volunteers in HIV prevention research in developing countries are evolving. Inconsistency in standards, particularly within a research network highlights the need to balance volunteers' health and wellness with the efficient conduct of research. Ten research centers (RC's) in East and Southern Africa affiliated with the International AIDS Vaccine Initiative (IAVI) were studied using a mixed methods approach to understand variations, similarities and gaps in services provided, recipients of services, referral systems, and barriers to referral uptake. These data were then used to develop expected standards across the 10 RCs. Findings indicated that RCs consistently provided HIV risk reduction and family planning (FP) counseling, male condoms, management of sexually transmitted infections, CD-4 counts, and general medical care to volunteers and non-research volunteers. Services that were less consistently provided on-site included: female condoms, adult male circumcision (AMC), antiretroviral therapy (ART) and post-exposure prophylaxis (PEP) in case of rape. The FP options provided on-site varied, with few providing implants, intrauterine devices, tubal ligation, and vasectomy. Most RCs had established referral systems for ART, AMC, PEP, and FP, but few had referral points for psychosocial services. Few RCs had comprehensive guidelines on referrals other than those related to adverse events. Findings indicate that the greatest challenges for referral uptake were transportation and health care costs, poor quality and inconsistency of services at some referral points. Few RCs covered the cost of referrals for non-study related adverse events. A collaborative process between IAVI and the RCs was undertaken to reach consensus on expected standards of care. A set of required and recommended services to be provided on-site or by referral was developed. In developing such standards, we tried to balance scientific priorities, equity, contextual realities, community expectations, and cost-effectiveness.

Objective: To estimate the potential impact of an HIV/AIDS Vaccine in Kenya. Design: The Kenyan HIV/AIDS epidemic was modeled using the most current data from national sources including epidemiology and behavioral surveillance. The model’s baseline projection was validated against adult HIV prevalence at antenatal clinics and general population surveys. The model was used to analyze the effects of scaling up current prevention programs and adding potential HIV vaccines with varying levels of effectiveness and coverage. Results: Even with full scale-up of currently available prevention, care and treatment programs, new infections will continue to burden Kenya. The introduction of a partially effective AIDS vaccine could significantly alter the trajectory of the epidemic. Conclusion: The game changing impact that an AIDS vaccine could have on the AIDS epidemic in Kenya under-scores the importance of sustaining political support and financial investment to accelerate HIV/AIDS vaccine research and development.

Background 1.5 million Kenyans are living with HIV/AIDS as per 2015 estimates. Though there is a notable decline in new HIV infections, continued effort is still needed to develop an efficacious, accessible and affordable HIV vaccine. HIV vaccine clinical trials bear risks, hence a need to understand volunteer motivators for enrolment, retention and follow-up. Understanding the factors that motivate volunteers to participate in a clinical trial can help to strategize, refine targeting and thus increase enrolment of volunteers in future HIV vaccine clinical trials. The health belief model classifies motivators into social benefits such as ‘advancing research’ and collaboration with science, and personal benefits such as health benefits and financial interests. Method A thematic analysis was carried out on data obtained from four HIV clinical trials conducted at KAVI-Institute of Clinical Research in Nairobi Kenya from 2009 to 2015. Responses were obtained from a Questionnaire administered to the volunteers during their screening visit at the research site. Results Of the 281 healthy, HIV-uninfected volunteers participating in this study; 38% were motivated by personal benefits including, 31% motivated by health benefits and 7% motivated by possible financial gains. In addition, 62% of the volunteers were motivated by social benefits with 20% of who were seeking to help their family/society/world while 42% were interested in advancing research. Conclusion The majority of volunteers in the HIV vaccine trials at our site were motivated by social benefits, suggesting that altruism can be a major contributor to participation in HIV vaccine studies. Personal benefits were a secondary motivator for the volunteers. The motivators to volunteer in HIV clinical trials were similar across ages, education level and gender. Education on what is needed (including volunteer participation) to develop an efficacious vaccine could be the key to greater volunteer motivation to participate in HIV vaccine clinical trials.

Background: Mucosal specimens are essential to evaluate compartmentalized immune responses to HIV vaccine candidates and other mucosally targeted investigational products. We studied the acceptability and feasibility of repeated mucosal sampling in East African clinical trial participants at low risk of HIV and other sexually transmitted infections. Methods and Findings: The Kenya AIDS Vaccine Initiative (KAVI) enrolled participants into three Phase 1 trials of preventive HIV candidate vaccines in 2011–2012 at two clinical research centers in Nairobi. After informed consent to a mucosal substudy, participants were asked to undergo collection of mucosal secretions (saliva, oral fluids, semen, cervico-vaginal and rectal), but could opt out of any collection at any visit. Specimens were collected at baseline and two additional time points. A tolerability questionnaire was administered at the final sub-study visit. Of 105 trial participants, 27 of 34 women (79%) and 62 of 71 men (87%) enrolled in the mucosal sub-study. Nearly all sub-study participants gave saliva and oral fluids at all visits. Semen was collected from about half the participating men (47–48%) at all visits. Cervico-vaginal secretions were collected by Softcup from about two thirds of women (63%) at baseline, increasing to 78% at the following visits, with similar numbers for cervical secretion collection by Merocel sponge; about half of women (52%) gave cervico-vaginal samples at all visits. Rectal secretions were collected with Merocel sponge from about a quarter of both men and women (24%) at all 3 visits, with 16% of men and 19% of women giving rectal samples at all visits. Conclusions: Repeated mucosal sampling in clinical trial participants in Kenya is feasible, with a good proportion of participants consenting to most sampling methods with the exception of rectal samples. Experienced staff members of both sexes and trained counselors with standardized messaging may improve acceptance of rectal sampling.

Background Volunteer understanding of trial concepts is a critical part of informed consent in clinical trials. Standard practice is to use closed-ended true/false forms to assess understanding; however such tools may overestimate understanding and most likely measure memory only. Open ended tools, such as scenarios, may be preferable. Following pilot studies that compared various methods of assessing understanding, a mixed method tool was developed by HAVEG, IAVI and partners. The tool employs both True/False questions for simpler concepts and open-ended scenarios for complex concepts.

Background: HIV rapid tests (RT) are a quick and non-technically demanding means to perform HIV voluntary counselling and testing (VCT) but understanding their limitations is vital to delivering quality VCT. Objective: To determine the sensitivity and specificity of HIV rapid tests used for research and voluntary counselling and testing at four sites in East Africa. Design: Cross-sectional study. Setting: Masaka District, Uganda; a sugar plantation in Kakira, Uganda; Coastal Villages in the Kilifi District of Kenya; and the Urban slum of Kangemi located West of Nairobi, Kenya. Subjects: Six thousands two hundred and fifty five consenting volunteers were enrolled into the study, and 675 prevalent HIV infections were identified. Results: The RT sensitivity tended to be high for all assays at all sites (97.63-100%) with the exception of the Uni-Gold assay (90.24% in Kangemi, 96.58% in Kilifi). Twenty four RT results were recorded as ‘weak positives\', 22 (92%) of which were negative by ELISA. There was a high rate of RT false positives in Uganda (positive predictive values ranging from 45.70% to 86.62%). Conclusions: The sensitivity and specificity of the RT varied significantly across sites. The rate of RT misclassification in Uganda suggests that a multiple test algorithm may be preferable to a single test as screener for HIV VCT. East African Medical Journal Vol. 85 (10) 2008: pp. 500-504

Methods The Kenya AIDS Vaccine Initiative (KAVI) initiated two AIDS preventive vaccine trials in Nairobi in 2011. After informed consent for a mucosal substudy, participants were asked to provide any of several types of mucosal secretions: saliva, oral fluids, semen, cervico-vaginal and rectal. Specimens were collected at baseline, one month after final vaccination, and at the next scheduled trial visit. A tolerability questionnaire was administered at the final visit.