Feasibility of conducting HIV prevention trials among key populations in Nairobi, Kenya.

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.

Willingness to participate in future HIV vaccine trials among men who have sex with men and female sex workers living in Nairobi, Kenya.

Objective: To 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.

Background: Working 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.

Reported willingness to participate in a hypothetical HIV vaccine trial and its translation to actual participation among healthy adults-Experience from Kenya.

Objective: To evaluate initial reported willingness to participate in a hypothetical HIV vaccine clinical trial and actual participation of volunteers in a longitudinal observational study.

Methods: We recruited HIV negative male and female volunteers aged 18-45 years into a longitudinal observational study at KAVI-ICR Kangemi in Kenya, to serve as a pool from which to draw participants into a phase I HIV vaccine clinical trial. A structured questionnaire was used to collect information regarding willingness to join a HIV vaccine clinical trial in the future.

Live Attenuated Zoster Vaccine Boosts Varicella Zoster Virus (VZV)-Specific Humoral Responses Systemically and at the Cervicovaginal Mucosa of Kenyan VZV-Seropositive Women.

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.

Integrin αβ expression on peripheral blood CD4 T cells predicts HIV acquisition and disease progression outcomes.

The gastrointestinal (GI) mucosa is central to HIV pathogenesis, and the integrin αβ promotes the homing of immune cells to this site, including those that serve as viral targets. Data from simian immunodeficiency virus (SIV) animal models suggest that αβ blockade provides prophylactic and therapeutic benefits. We show that pre-HIV infection frequencies of αβ peripheral blood CD4 T cells, independent of other T cell phenotypes and genital inflammation, were associated with increased rates of HIV acquisition in South African women.

Afri-Can Forum 2 : Johannesburg, South Africa. 16-18 February 2015.

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.

Early HIV-1 infection is associated with reduced frequencies of cervical Th17 cells.

Background: The hallmark of HIV infection is progressive but variable rates of systemic and mucosal CD4 depletion, leading to immunodeficiency. The impact of early HIV infection on cervical CD4 T-cell populations in humans remains poorly described.

Methods: We analyzed cytobrush-derived immune cells by flow cytometry and cytokines in cervicovaginal lavage from participants in early HIV (<6 months postinfection), chronic HIV, and HIV-uninfected controls.

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.

Characterization of a human cervical CD4+ T cell subset coexpressing multiple markers of HIV susceptibility.

The HIV pandemic disproportionately affects women, with most infections acquired through receptive vaginal sex. Although the target cells by which HIV establishes infection in the female genital tract remain poorly defined, it is known that immune activation results in CD4(+) T cells with enhanced susceptibility, as does expression of the mucosal integrin α4β7 and the HIV coreceptor CCR5. Blood and cervical cytobrush specimens were collected from female sex workers (FSWs) in Nairobi, Kenya.

Epitope cross-reactivity frequently differs between central and effector memory HIV-specific CD8+ T cells.

HIV diversity may limit the breadth of vaccine coverage due to epitope sequence differences between strains. Although amino acid substitutions within CD8(+) T cell HIV epitopes can result in complete or partial abrogation of responses, this has primarily been demonstrated in effector CD8(+) T cells. In an HIV-infected Kenyan cohort, we demonstrate that the cross-reactivity of HIV epitope variants differs dramatically between overnight IFN-gamma and longer-term proliferation assays.

Characterization of intersubtype recombinant HIV type 1 genomes using a nonradioactive heteroduplex tracking assay.

The HIV-1 epidemic is characterized by the dominance of distinct viral subtypes in different regions of the world, and intersubtype recombinants are common. Traditional subtyping methods analyze only a small fragment of the HIV-1 genome, so the true extent of diversity and recombination has been difficult to examine. We developed a heteroduplex tracking assay (HTA) to identify viral subtypes and rapidly detect recombinant HIV-1 genomes.

Construction of an infectious HIV type 1 molecular clone from an African patient with a subtype D/C Recombinant Virus.

The majority of HIV-1 infections worldwide occur in Africa, where subtype B viruses are rare and intersubtype recombinants are common. Pathogenesis and vaccine studies need to focus on viruses derived from African patients, and infectious HIV-1 molecular clones can be useful tools. To clone non-B subtypes and recombinant viruses from patients, we cultivated HIV-1 from the plasma of a Kenyan long-term survivor.

Long-term survivors in Nairobi: complete HIV-1 RNA sequences and immunogenetic associations.

To investigate African long-term survivors (LTSs) infected with non-subtype B human immunodeficiency virus type 1 (HIV-1), we obtained full-length HIV-1 RNA sequences and immunogenetic profiles from 6 untreated women enrolled in the Pumwani Sex Worker Cohort in Nairobi, Kenya. There were no discernible sequence changes likely to cause attenuation. CCR2-V64I, an immunogenetic polymorphism linked to LTSs, was detected in 4 women, all of whom carried the HLA B58 allele.

Acute sexually transmitted infections increase human immunodeficiency virus type 1 plasma viremia, increase plasma type 2 cytokines, and decrease CD4 cell counts.

In Kenya, the median incubation time to AIDS in seroconverting sex workers is 4 years; this incubation time is specific to female sex workers. We studied the influence of acute sexually transmitted infections (STIs) on several immunologic parameters in 32 human immunodeficiency virus type 1 (HIV-1)-positive and 10 HIV-1-negative women sex workers who were followed for 1-5 months. Plasma cytokines, soluble cytokine receptors, CD4 and CD8 T cell counts, and HIV-1 plasma viremia were quantitated before, during, and after episodes of STI.

Effect of human immunodeficiency virus (HIV) type 1 viral genotype on mother-to-child transmission of HIV-1.

The objective of this study was to determine whether the maternal infecting human immunodeficiency virus (HIV) type 1 clade affects mother-to-child transmission frequency. Mothers in the mother-to-child HIV-1 transmission study in Nairobi, Kenya, were grouped by HIV-1 status of their first enrolled child: uninfected, perinatally infected, or postnatally infected. Restriction fragment length polymorphism (RFLP) analysis was used to determine HIV-1 viral clades of nested polymerase chain reaction products from HIV-1 protease or p24 genes.

Naturally occurring IgG anti-HLA alloantibody does not correlate with HIV type 1 resistance in Nairobi prostitutes.

In an effort to identify an immunological basis for natural resistance to HIV-1 infection, we have examined serum antibody responses to HLA class I antigens in female prostitutes of the Nairobi Sex Workers Study. Anti-HLA antibodies are known to block HIV infectivity in vitro and can be protective against SIV challenge in macaques immunized with purified class I HLA. Thus, it was postulated that broadly cross-reactive alloantibodies recognizing common HLA alleles in the client population might contribute to the prevention of heterosexual transmission of HIV.

Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Kenya.

Background: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection.

Comparison of the declines in CD4 counts in HIV-1-seropositive female sex workers and women from the general population in Nairobi, Kenya.

Studies from Kenya have reported rapid clinical disease progression among HIV-infected professional sex workers. The reasons for this rapid decline are unknown. To better understand factors influencing the course of disease, HIV-1 disease progression was explored in terms of declines in CD4 counts.

Low dose erythromycin regimen for the treatment of chancroid.

Haemophilus ducreyi is the commonest cause of genital ulcer disease in Africa and is associated with heterosexual transmission of human immunodeficiency virus(HIV). The World Health Organization currently recommends erythromycin 500 mg three times a day for seven days as the treatment of choice for Haemophilus ducreyi infection. We studied the effectiveness of a lower dose erythromycin treatment regime, 250 mg three times a day for seven days in the treatment of chancroid.

Breastfeeding and immunity to intestinal infections.

The purpose of this study was to compare immune response in breast and non breastfed children presenting with diarrhoea at Paediatric Observation Ward, Kenyatta National Hospital (KNH-POW) and Maternal and Child Health Clinic, Pumwani Maternity Hospital (PMH-MCH). Blood and stool samples were collected from the first four consecutive children aged 5 years and below per day, presenting with or without diarrhoea from January to December, 1992. The stools were tested for total IgA by single radial immunodiffusion (SRID) and specific IgA by enzyme linked immunosorbent assay (ELISA).

Controlling HIV in Africa: effectiveness and cost of an intervention in a high-frequency STD transmitter core group.

Since 1985, a population of over 1,000 predominantly HIV-positive female prostitutes residing in a low-income area of Nairobi, has been enrolled in a sexually transmitted disease (STD)/HIV control programme. The major elements of the programme include the diagnosis and treatment of conventional STD, and the promotion of condom use to prevent the transmission of HIV and other sexually transmitted infections. Using estimates of numbers of HIV-seropositive prostitutes, numbers of sexual contacts, susceptibility of clients to HIV, HIV transmission efficiency, rates of condom use and the basic reproductive rate of HIV infection in Kenya, we estimate that the programme is responsible for preventing between 6,000 and 10,000 new cases of HIV infection per year among clients and contacts of clients.

Transition dynamics of HIV disease in a cohort of African prostitutes: a Markov model approach.

The progression of HIV-related disease from infection to death is represented as a staged Markov model. Transitions between stages are considered reversible. The model is fitted to data from a cohort of African prostitutes by means of maximum likelihood.