The impact of B-cell-directed therapy on SARS-CoV-2 vaccine efficacy in chronic lymphocytic leukaemia.

Prior reports evaluating SARS-CoV-2 vaccine efficacy in chronic lymphocytic leukaemia (CLL) used semiquantitative measurements of anti-S to evaluate immunity; however, neutralization assays were used to assess functional immunity in the trials leading to vaccine approval. Here, we identified decreased rates of seroconversion in vaccinated CLL patients and lower anti-S levels compared to healthy controls. Notably, we demonstrated similar results with the Roche anti-S assay and neutralization activity. Durable responses were seen at six months; augmentation with boosters was possible in responding patients. Absence of normal B cells, frequently seen in patients receiving Bruton tyrosine kinase and B-cell lymphoma 2 inhibitors, was a strong predictor of lack of seroconversion.

Prevalence and correlates of HIV infection among adolescents and young people living in fishing populations along Lake Victoria Fishing Communities in Uganda.

INTRODUCTION: fishing communities in Uganda are key populations for HIV, with persistently higher prevalence and incidence than the general population. METHODS: between March and August 2014, a cross sectional survey was conducted in 10 fishing communities of Lake Victoria in Uganda. Data was collected on socio-behavioural characteristics using interviewer administered questionnaires and venous blood collected for HIV testing. Prevalent HIV infections among adolescents and young people aged 13 to 24 years was estimated and the factors associated with those infections determined using multi variable logistic regression modelling. RESULTS: HIV prevalence was 10.8% among the 630 (96.5%) who provided a blood sample. Females were 3.5 times as likely to have HIV infection as males (aOR=3.52, 95% CI: 1.34-9.22). Young people aged 20-24 years were twice as likely to be HIV infected as those aged 13-19 years (aOR=1.77, 95% CI: 0.05-2.10), participants without formal education or those who had studied up to primary level were more likely to be HIV infected than those who had post primary education ((aOR=2.45, 95% CI: 1.19-5.07) or (5.29 (1.35-20.71) respectively). Reporting more than one sexual partner in the past 6 months was associated with HIV prevalent infection than those reporting no sexual partners (aOR=6.44, 95% CI: 1.27-32.83). CONCLUSION: adolescents and young people aged 13-24 years in fishing communities around Lake Victoria, Uganda, have a high HIV prevalence, with females having a three-fold higher level than males. These findings highlight-the need to improve HIV prevention among young females living in these fishing communities.

HIV prevalence, spatial distribution and risk factors for HIV infection in the Kenyan fishing communities of Lake Victoria.

INTRODUCTION: Global efforts to end HIV by 2030 focus on reducing and eventually eliminating new infections in priority populations. Identifying these populations and characterizing their vulnerability factors helps in guiding investment of scarce HIV prevention resources to achieve maximum impact. We sought to establish HIV prevalence, spatial distribution and risk factors for HIV infection in the Kenyan fishing communities of Lake Victoria. METHODS: We conducted a cross-sectional survey of 2637 people from all the 308 fish-landing beaches on the Kenyan shore of Lake Victoria. The number of participants enrolled at each beach were weighted based on the size of the beach, determined by the number of functional registered boats. We used simple random sampling to select those to be approached for study participation. Consenting participants were privately interviewed about their socio-economic and demographic characteristics and sexual behavior, and were invited for HIV test using the Kenya rapid HIV testing protocol. We used descriptive statistics and multivariate logistic and linear regression for analysis. RESULTS: We found high HIV prevalence of 32% with significant differences between men (29%) and women (38%). Among men, having an HIV negative sexual partner, being circumcised, increasing number of condom protected sex acts in the preceding month, being younger and being a resident of Homa Bay, Kisumu, Siaya and Busia counties compared to Migori County reduced the risk of HIV infection. For women, being married, having more children with the current spouse, having an HIV negative sexual partner and being a resident of Busia compared to Migori County reduced the risk of HIV infection. We also found that longer distance from the beaches to the nearest public health facilities was associated with increasing cumulative HIV prevalence at the beaches. CONCLUSION: Fishing communities have high HIV prevalence and may greatly benefit from interventions such as wider ART coverage, couple HIV risk reduction counseling, PrEP use for HIV negative partner at substantial continuous risk, alongside other HIV prevention services that the Kenyan government is currently rolling out. This will additionally require adequate plans to synchronize the provision of these services with the population's routine schedules for all these options to be reasonably accessible to them.

Effect of Schistosoma mansoni Infection on Innate and HIV-1-Specific T-Cell Immune Responses in HIV-1-Infected Ugandan Fisher Folk.

In Uganda, fisher folk have HIV prevalence rates, about four times higher than the national average, and are often coinfected with Schistosoma mansoni. We hypothesized that innate immune responses and HIV-specific Th1 immune responses might be downmodulated in HIV/S. mansoni-coinfected individuals compared with HIV+/S. mansoni-negative individuals. We stimulated whole blood with innate receptor agonists and analyzed supernatant cytokines by Luminex. We evaluated HIV-specific responses by intracellular cytokine staining for IFN-γ, IL-2, and TNF-α. We found that the plasma viral load and CD4 count were similar between the HIV+SM+ and HIV+SM- individuals. In addition, the TNF-α response to the imidazoquinoline compound CL097 and ß-1, 3-glucan (curdlan), was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. The frequency of HIV-specific IFN-γ+IL-2-TNF-α- CD8 T cells and IFN-γ+IL-2-TNF-α+ CD4 T cells was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. These findings do not support the hypothesis that S. mansoni downmodulates innate or HIV-specific Th1 responses in HIV/S. mansoni-coinfected individuals.

Factors associated with dropout in a long term observational cohort of fishing communities around lake Victoria, Uganda.

BACKGROUND: Fishing communities are potentially suitable for Human immunodeficiency virus (HIV) efficacy trials due to their high risk profile. However, high mobility and attrition could decrease statistical power to detect the impact of a given intervention. We report dropout and associated factors in a fisher-folk observational cohort in Uganda. METHODS: Human immunodeficiency virus-uninfected high-risk volunteers aged 13-49 years living in five fishing communities around Lake Victoria were enrolled and followed every 6 months for 18 months at clinics located within each community. Volunteers from two of the five communities had their follow-up periods extended to 30 months and were invited to attend clinics 10-40 km (km) away from their communities. Human immunodeficiency virus counseling and testing was provided, and data on sexual behaviour collected at all study visits. Study completion was defined as completion of 18 or 30 months or visits up to the date of sero-conversion and dropout as missing one or more visits. Discrete time survival models were fitted to find factors independently associated with dropout. RESULTS: A total of 1000 volunteers (55% men) were enrolled. Of these, 91.9% completed 6 months, 85.2% completed 12 months and 76.0% completed 18 months of follow-up. In the two communities with additional follow-up, 76.9% completed 30 months. In total 299 (29.9%) volunteers missed at least one visit (dropped out). Dropout was independently associated with age (volunteers aged 13-24 being most likely to dropout), gender [men being more likely to dropout than women [adjusted hazard ratio (aHR) 1.4; 95% confidence interval (CI) 1.1-1.8)], time spent in the fishing community (those who stayed <1 year being most likely to dropout), History of marijuana use (users being more likely to dropout than non-users [1.7; (1.2-2.5)], ethnicity (non-Baganda being more likely to dropout than Baganda [1.5; (1.2-1.9)], dropout varied between the five fishing communities, having a new sexual partner in the previous 3 months [1.3 (1.0-1.7)] and being away from home for ≥2 nights in the month preceding the interview [1.4 (1.1-1.8)]. CONCLUSION: Despite a substantial proportion dropping out, retention was sufficient to suggest that by incorporating retention strategies it will be possible to conduct HIV prevention efficacy trials in this community.

Use of Modern Family Planning Methods in Fishing Communities of Lake Victoria, Uganda.

INTRODUCTION: Fishing communities (FCs) in Uganda have high HIV infection rates but poor access to health services including family planning (FP). Although FP is a cost-effective public health intervention, there is a paucity of data on knowledge and use of modern FP in FCs. This study determined knowledge and use of modern FP methods in FCs of Uganda. METHODS: Data were accrued from a 12-month follow up of 1,688 HIV-uninfected individuals, 18-49 years from 8 FCs along Lake Victoria, between September 2011 and March 2013. Data on knowledge and use of modern FP were collected through a semi-structured questionnaire. Prevalence Risk Ratios with corresponding 95% CIs were used to determine factors associated with Modern FP knowledge and use. RESULTS: The mean age was 31.4 years, with nearly half (48.8%) being females while more than half (58.6%) had attained up to primary education level. Knowledge of modern FP was high, 87.5% (1477/1688); significantly higher among females [adj. PRR = 4.84 (95% CI; 3.08, 7.61)], among older respondents (25-29 years) [adj. PRR = 1.83 (95% CI; 1.12, 2.99)] compared to younger ones (18-24 years) and among those conducting business [adj. PRR = 2.42(95% CI; 1.02, 5.74)] relative to those primarily in fishing. Just over a third (35.2%, 595/1688) reported use of at least one modern FP method. Use of modern FP methods was significantly higher among females [adj. PRR = 2.04 (95% CI; 1.56, 2.65, and among those reporting multiple sexual partnerships [adj. PRR = 2.12, 95% CI; 1.63, 2.76)]. Nonuse of modern methods was mostly due to desire for more children (30.6%), fear of side effects (12.2%) and partner refusal (5.2%). CONCLUSION: Despite their high knowledge of FP, FCs have low use of modern FP methods. Key barriers to use of modern FP methods were high fertility desires, fear of perceived side effects and partner refusal of methods.

Recruitment and retention of women in fishing communities in HIV prevention research.

INTRODUCTION: Women in fishing communities in Uganda are more at risk and have higher rates of HIV infection. Socio-cultural gender norms, limited access to health information and services, economic disempowerment, sexual abuse and their biological susceptibility make women more at risk of infection. There is need to design interventions that cater for women's vulnerability. We explore factors affecting recruitment and retention of women from fishing communities in HIV prevention research. METHODS: An HIV incidence cohort screened 2074 volunteers (1057 men and 1017 women) aged 13-49 years from 5 fishing communities along Lake Victoria using demographic, medical history, risk behaviour assessment questionnaires.1000 HIV negative high risk volunteers were enrolled and followed every 6 months for 18 months. Factors associated with completion of study visits among women were analyzed using multivariable logistic regression. RESULTS: Women constituted 1,017(49%) of those screened, and 449(45%) of those enrolled with a median (IQR) age of 27 (22-33) years. Main reasons for non-enrolment were HIV infection (33.9%) and reported low risk behaviour (37.5%). A total of 382 (74%) women and 332 (69%) men completed all follow up visits. Older women (>24 yrs) and those unemployed, who had lived in the community for 5 years or more, were more likely to complete all study visits. CONCLUSION: Women had better retention rates than men at 18 months. Strategies for recruiting and retaining younger women and those who have stayed for less than 5 years need to be developed for improved retention of women in fishing communities in HIV prevention and research Programs.

Schistosoma mansoni Infection in Ugandan Men Is Associated with Increased Abundance and Function of HIV Target Cells in Blood, but Not the Foreskin: A Cross-sectional Study.

BACKGROUND: Schistosoma mansoni infection has been associated with an increased HIV prevalence in humans and SHIV incidence in primate models. We hypothesized that immune activation from this gastrointestinal mucosa infection would increase highly HIV-susceptible CD4 T cell subsets in the blood and the foreskin through common mucosal homing. METHODOLOGY/PRINCIPAL FINDINGS: Foreskin tissue and blood were obtained from 34 HIV- and malaria-uninfected Ugandan men who volunteered for elective circumcision, 12 of whom were definitively positive for S. mansoni eggs in stool and 12 definitively negative for both S. mansoni eggs and worm antigen. Tissue and blood T cell subsets were characterized by flow cytometry and immunohistochemistry (IHC). Th17 and Th1 cells from both the blood and foreskin expressed higher levels of CCR5 and were more activated than other CD4 T cell subsets. S. mansoni-infected men had a higher frequency of systemic Th1 cells (22.9 vs. 16.5% of blood CD4 T cells, p<0.05), Th17 cells (2.3 vs. 1.5%, p<0.05), and Th22 cells (0.5 vs. 0.3%, p<0.01) than uninfected men. Additionally, Th17 cells in the blood of S. mansoni-infected men demonstrated enhanced function (28.1 vs. 16.3% producing multiple cytokines, p = 0.046). However, these immune alterations were not observed in foreskin tissue. CONCLUSIONS/SIGNIFICANCE: S. mansoni infection was associated with an increased frequency of highly HIV-susceptible Th1, Th17 and Th22 cell subsets in the blood, but these T cell immune differences did not extend to the foreskin. S. mansoni induced changes in T cell immunology mediated through the common mucosal immune system are not likely to increase HIV susceptibility in the foreskin.

Schistosoma mansoni and HIV acquisition in fishing communities of Lake Victoria, Uganda: a nested case-control study.

OBJECTIVE: It has been suggested that Schistosoma mansoni, which is endemic in African fishing communities, might increase susceptibility to human immunodeficiency virus (HIV) acquisition. If confirmed, this would be of great public health importance in these high HIV-risk communities. This study was undertaken to determine whether S. mansoni infection is a risk factor for HIV infection among the fishing communities of Lake Victoria, Uganda. We conducted a matched case-control study, nested within a prospective HIV incidence cohort, including 50 HIV seroconverters (cases) and 150 controls during 2009-2011. METHODS: S. mansoni infection prior to HIV seroconversion was determined by measuring serum circulating anodic antigen (CAA) in stored serum. HIV testing was carried out using the Determine rapid test and infection confirmed by enzyme-linked immunosorbent assays. RESULTS: About 49% of cases and 52% of controls had S. mansoni infection prior to HIV seroconversion (or at the time of a similar study visit, for controls): odds ratio, adjusting for ethnicity, religion, marital status, education, occupation, frequency of alcohol consumption in previous 3 months, number of sexual partners while drunk, duration of stay in the community, and history of schistosomiasis treatment in the past 2 years was 1.23 (95% CI 0.3-5.7) P = 0.79. S. mansoni infections were chronic (with little change in status between enrolment and HIV seroconversion), and there was no difference in median CAA concentration between cases and controls. CONCLUSIONS: These results do not support the hypothesis that S. mansoni infection promotes HIV acquisition.

High incidence of HIV-1 infection in a general population of fishing communities around Lake Victoria, Uganda.

BACKGROUND: High HIV-1 incidence rates were reported among persons in fisherfolk communities (FFC) in Uganda who were selected for high risk behaviour. We assessed the incidence of HIV-1 and associated risk factors in a general population FFC to determine population-wide HIV rates. METHODS: A community-based cohort study was conducted among a random sample of 2191 participants aged 18-49 years. At baseline and 12 months post-baseline, data were collected on socio-demographic characteristics and risky behaviors (including number of partners, new partners, condom use, use of alcohol and illicit drug use). Venous blood was collected for HIV serological testing. HIV incidence was calculated per 100 person years at-risk (pyar) and adjusted incidence rate ratios (Adj.IRR) were estimated by multivariable Poisson regression. RESULTS: Overall follow up at 12 months was 76.9% (1685/2191) and was significantly higher among HIV uninfected persons and those with at least 1 year duration of stay in community. Overall HIV-1 incidence was 3.39/100 pyar (95% CI: 2.55-4.49). Among the 25-29 years who drank alcohol, HIV incidence was 7.67/100 pyar (95% CI;4.62-12.7) while it was 5.67/100 pyar (95% CI;3.14-10.2) for 18-24 year olds who drank alcohol. The risk of HIV infection was higher among 25-29 years (adj.IRR = 3.36; 95% CI: 1.48-7.65) and 18-24 years (adj.IRR = 2.65; 95% CI: 1.05-6.70) relative to 30+ years. Compared to non-drinkers, HIV incidence increased by frequency of alcohol drinking--occasional drinkers (adj.IRR = 3.18; 95% CI: 1.18-8.57) and regular drinkers (adj.IRR = 4.93; 95% CI: 1.91-12.8). CONCLUSION: HIV-1 incidence in general fisherfolk population along L. Victoria, Uganda, is high and is mainly associated with young age and alcohol drinking. HIV prevention and control strategies are urgently needed in this population.

Characterization of neutrophil subsets in healthy human pregnancies.

We have previously shown that in successful pregnancies increased arginase activity is a mechanism that contributes to the suppression of the maternal immune system. We identified the main type of arginase-expressing cells as a population of activated low-density granulocytes (LDGs) in peripheral blood mononuclear cells and in term placentae. In the present study, we analyzed the phenotype of LDGs and compared it to the phenotype of normal density granulocytes (NDGs) in maternal peripheral blood, placental biopsies and cord blood. Our data reveal that only LDGs but no NDGs could be detected in placental biopsies. Phenotypically, NDGs and LDGs from both maternal and cord blood expressed different levels of maturation, activation and degranulation markers. NDGs from the maternal and cord blood were phenotypically similar, while maternal, cord and placental LDGs showed different expression levels of CD66b. LDGs present in cord blood expressed higher levels of arginase compared to maternal and placental LDGs. In summary, our results show that in maternal and cord blood, two phenotypically different populations of neutrophils can be identified, whereas in term placentae, only activated neutrophils are present.

High HIV-1 prevalence, risk behaviours, and willingness to participate in HIV vaccine trials in fishing communities on Lake Victoria, Uganda.

INTRODUCTION: HIV epidemics in sub-Saharan Africa are generalized, but high-risk subgroups exist within these epidemics. A recent study among fisher-folk communities (FFC) in Uganda showed high HIV prevalence (28.8%) and incidence (4.9/100 person-years). However, those findings may not reflect population-wide HIV rates in FFC since the study population was selected for high-risk behaviour. METHODS: Between September 2011 and March 2013, we conducted a community-based cohort study to determine the population representative HIV rates and willingness to participate (WTP) in hypothetical vaccine trials among FFC, Uganda. At baseline (September 2011-January 2012), a household enumeration census was done in eight fishing communities (one lakeshore and seven islands), after which a random sample of 2200 participants aged 18-49 years was selected from 5360 individuals. Interviewer-administered questionnaire data were collected on HIV risk behaviours and WTP, and venous blood was collected for HIV testing using rapid HIV tests with enzyme-linked immunosorbent assay (EIA) confirmation. Adjusted prevalence proportion ratios (adj.PPRs) of HIV prevalence were determined using log-binomial regression models. RESULTS: Overall baseline HIV prevalence was 26.7% and was higher in women than men (32.6% vs. 20.8%, p<0.0001). Prevalence was lower among fishermen (22.4%) than housewives (32.1%), farmers (33.1%) and bar/lodge/restaurant workers (37%). The adj.PPR of HIV was higher among women than men (adj.PPR =1.50, 95%; 1.20, 1.87) and participants aged 30-39 years (adj.PPR=1.40, 95%; 1.10, 1.79) and 40-49 years (adj.PPR=1.41, 95%; 1.04, 1.92) compared to those aged 18-24 years. Other factors associated with HIV prevalence included low education, previous marriage, polygamous marriage, alcohol and marijuana use before sex. WTP in hypothetical vaccine trials was 89.3% and was higher in men than women (91.2% vs. 87.3%, p=0.004) and among island communities compared to lakeshore ones (90.4% vs. 85.8%, p=0.004). CONCLUSIONS: The HIV prevalence in the general fisher-folk population in Uganda is similar to that observed in the "high-risk" fisher folk. FFC have very high levels of willingness to participate in future HIV vaccine trials.

Short communication: HIV type 1 transmitted drug resistance and evidence of transmission clusters among recently infected antiretroviral-naive individuals from Ugandan fishing communities of Lake Victoria.

Human immunodeficiency virus type 1 (HIV-1) prevalence and incidence in the fishing communities on Lake Victoria in Uganda are high. This population may play a role in driving the HIV epidemic in Uganda including the spread of transmitted drug resistance (TDR). We report data on TDR in this population among antiretroviral (ARV)-naive, recently infected individuals about 5 years after ARV scaling-up in Uganda. We identified phylogenetic transmission clusters and combined these with volunteer life histories in order to understand the sexual networks within this population. From a prospective cohort of 1,000 HIV-negative individuals recruited from five communities, 51 seroconverters were identified over a period of 2 years. From these, whole blood was collected and population sequencing of the HIV-1 pol gene (protease/reverse transcriptase) was performed from plasma. Drug resistance mutations (DRMs) were scored using the 2009 WHO list for surveillance of TDR. TDR prevalence categories were estimated using the WHO recommended truncated sampling technique for the surveillance of TDR for use in resource-limited settings (RLS). Of the samples 92% (47/51) were successfully genotyped. HIV-1 subtype frequencies were 15/47 (32%) A1, 20/47 (43%) D, 1/47 (2%) C, 1/47 (2%) G, and 10/47 (21%) unique recombinant forms. Nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutation K103N was identified in two individuals and V106A in one (6%) suggesting that the level of TDR was moderate in this population. No nucleoside/tide reverse transcriptase inhibitor (NRTI) or protease inhibitor (PI) DRMs were detected. In this study, we identified five transmission clusters supported by high bootstrap values and low genetic distances. Of these, one pair included the two individuals with K103N. Two of the genotypic clusters corresponded with reported sexual partnerships as detected through prior in-depth interviews. The level of TDR to NNRTIs in these ARV-naive individuals was moderate by WHO threshold survey categorization. The transmission clusters suggest a high degree of sexual partner mixing between members of these communities.

High HIV incidence and socio-behavioral risk patterns in fishing communities on the shores of Lake Victoria, Uganda.

BACKGROUND: We report on HIV acquisition and its associated risk factors in 5 fishing communities on the shores of Lake Victoria in Uganda. A cohort of 1000 HIV-uninfected at-risk volunteers aged 13 to 49 years were recruited in 2009 and followed up for 18 months. METHODS: At enrollment and semiannual visits, socio-demographic and risk behavior data were collected through a structured questionnaire and blood samples tested for HIV and syphilis. Detailed life histories were collected from 78 volunteers using in-depth interviews. RESULTS: Of the 1000 volunteers enrolled, 919 (91.9%) were followed up, with 762 (76.2%) reaching the study end points (either seroconverted or completed 4 visits). There were 59 incident cases in 1205.6 person-years at risk (PYAR), resulting in an incidence rate of 4.9 (95% CI = 3.8 to 6.3) per 100 PYAR. The highest HIV incidence rates were among those working in bars (9.8/100 PYAR [4.7-20.6]), protestants (8.6/100 PYAR [5.8-12.7]), those aged 13 to 24 years (7.5/100 PYAR [5.2-11.0]), and new immigrants (6.6/100 PYAR [4.9-8.9]). HIV infection was independently associated with being young (adjusted hazard ratio (aHR) = 2.5 [95% CI = 1.3-4.9]), reporting genital sores/discharge recently (aHR = 2.8 [1.6-5.0]), regular alcohol consumption (aHR = 3.3 [1.6-6.1]), use of marijuana (aHR = 2.9 [1.0-8.0]), cigarette smoking (aHR = 3.6 [1.4-9.3]), and religion (compared with Catholics, Protestants had aHR = 2.7 [1.4-5.3] and Muslims had aHR = 2.3 [1.1-4.8]). CONCLUSIONS: These fishing communities experienced high HIV infection, which was mainly explained by high-risk behavior. There is an urgent need to target HIV prevention and research efforts to this vulnerable and neglected group.

HIV and syphilis prevalence and associated risk factors among fishing communities of Lake Victoria, Uganda.

OBJECTIVES: Recent publications suggest that fishing populations may be highly affected by the HIV epidemic. However, accurate data are scarce. The authors determined HIV and syphilis prevalence and associated risk factors in a fishing population of Lake Victoria in Uganda. METHODS: 10,188 volunteers aged ≥ 13 years from a census carried out in five fishing communities between February and August 2009 were invited to attend central study clinics established in each community. After informed consent, 2005 randomly selected volunteers responded to socio-demographic and risk assessment questions, provided blood for HIV testing and 1618 volunteers were also tested for syphilis. Risk factors were analysed using logistic regression. RESULTS: HIV and active syphilis (rapid plasma reagin titre ≥ 1:8) prevalences were 28.8% (95% CI 26.8 to 30.8) and 4.3% (95% CI 3.3 to 5.4), respectively, and high risk sexual behaviour was frequently reported. HIV prevalence was independently associated with female sex, increasing age, occupation (highest in fishermen), relationship to household head, self-reported genital sores and knowledge of an HIV infected partner. Alcohol consumption, syphilis and sexually transmitted infections (STIs) reported by health workers were associated with HIV in women, and genital discharge and inconsistent condom use in men. Syphilis prevalence was independently associated with age and alcohol consumption in women, and recent genital sores and sex under the influence of drugs in men. CONCLUSION: This fishing population characterised by a very high HIV prevalence, high syphilis prevalence and frequently reported sexual risk behaviours, urgently needs improved STI services and targeted behavioural interventions.

Safety and immunogenicity of recombinant low-dosage HIV-1 A vaccine candidates vectored by plasmid pTHr DNA or modified vaccinia virus Ankara (MVA) in humans in East Africa.

The safety and immunogenicity of plasmid pTHr DNA, modified vaccinia virus Ankara (MVA) human immunodeficiency virus type 1 (HIV-1) vaccine candidates were evaluated in four Phase I clinical trials in Kenya and Uganda. Both vaccines, expressing HIV-1 subtype A gag p24/p17 and a string of CD8 T-cell epitopes (HIVA), were generally safe and well-tolerated. At the dosage levels and intervals tested, the percentage of vaccine recipients with HIV-1-specific cell-mediated immune responses, assessed by a validated ex vivo interferon gamma (IFN-gamma) ELISPOT assay and Cytokine Flow Cytometry (CFC), did not significantly differ from placebo recipients. These trials demonstrated the feasibility of conducting high-quality Phase 1 trials in Africa.