Safety and immunogenicity study of Multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa.

Background: We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults.

Methodology/principal Findings: Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×10(10) or 1×10(11) particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months.

Characterization of an HLA-C-restricted CTL response in chronic HIV infection.

HIV-specific CTL play an important role in the host control of HIV infection. HIV-nef may facilitate escape of HIV-infected cells from CTL recognition by selectively downregulating the expression of HLA-A and HLA-B molecules, while surface expression of HLA-C is unaffected. The HLA-C-restricted CTL responses have previously been largely ignored and poorly characterized.

Serologic testing algorithm for recent HIV seroconversion in estimating incidence of HIV-1 among adults visiting a VCT centre at a Kenyan tertiary health institution.

Objective: To determine HIV high risk groups among adults visiting Kenyatta National Hospital Voluntary Counselling and Testing Centre by use of Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS).

Design: A cross-sectional study of adults.

Setting: Kenyatta National Hospital Voluntary and Counselling Centre.

Mucosal Neisseria gonorrhoeae coinfection during HIV acquisition is associated with enhanced systemic HIV-specific CD8 T-cell responses.

Background: The host immune response against mucosally acquired pathogens may be influenced by the mucosal immune milieu during acquisition. As Neisseria gonorrhoeae can impair dendritic cell and T-cell immune function, we hypothesized that coinfection during HIV acquisition would impair subsequent systemic T-cell responses.

Methods: Monthly screening for sexually transmitted infections was performed in high risk, HIV seronegative Kenyan female sex workers as part of an HIV prevention trial.

An evaluation of intravaginal rings as a potential HIV prevention device in urban Kenya: behaviors and attitudes that might influence uptake within a high-risk population.

Purpose: We sought to assess the potential acceptability of intravaginal rings (IVRs) as an HIV prevention method among at-risk women and men.

Methods: We conducted a qualitative assessment of initial attitudes toward IVRs, current HIV prevention methods, and common behavioral practices among female sex workers (FSWs) and men who frequent FSWs in Mukuru, an urban slum community in Nairobi, Kenya. Nineteen women and 21 men took part in six focus group discussions.

Coinfection with herpes simplex virus type 2 is associated with reduced HIV-specific T cell responses and systemic immune activation.

Background: Chronic coinfection with herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) has been associated with an increased HIV viral load and more rapid disease progression, perhaps related to HSV-2-associated alterations in host immunity.

Methods: Studies were nested within (1) a cross-sectional study of men coinfected with HIV and HSV-2 and (2) women not infected with HIV, both before and after HSV-2 acquisition. HSV-2 infection status was determined by ELISA.

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.

HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers.

Objectives: HIV-neutralizing immunoglobulin A (IgA) and HIV-specific cellular immunity have been described in highly exposed, persistently seronegative (HEPS) individuals, but well controlled studies have not been performed. We performed a prospective, nested case-control study to examine the association of genital IgA and systemic cellular immune responses with subsequent HIV acquisition in high-risk Kenyan female sex workers (FSWs).

Design And Methods: A randomized trial of monthly antibiotic prophylaxis to prevent sexually transmitted disease/HIV infection was performed from 1998 to 2002 in HIV-uninfected Kenyan FSWs.

HIV-1 neutralizing activity is correlated with increased levels of chemokines in saliva of HIV-1-exposed uninfected individuals.

Aim: Mucosal HIV-1 exposure stimulates a variety of mucosal immune responses, including IgA1-mediated virus neutralization, even in the absence of an established infection. We hypothesized that other immune molecules might also contribute to the HIV-1 neutralizing activity observed in the mucosal secretions of HIV-1 exposed uninfected individuals.

Methods: Saliva samples were collected from HIV-1 seronegative high-risk female sex workers (FSW) from Nairobi.

Persistently HIV-1 seronegative Nairobi sex workers are susceptible to in vitro infection.

Objective: To evaluate whether resistance to HIV-1 infection in a subset of highly exposed sex workers correlates with resistance at the cellular level.

Design: In vitro evaluation of susceptibility to infection by Kenyan HIV-1 isolates and cellular production of potential mediators of resistance.

Setting: Samples were collected in a primary care clinic in Nairobi.

Prevalent herpes simplex virus type 2 infection is associated with altered vaginal flora and an increased susceptibility to multiple sexually transmitted infections.

Background: Prevalent herpes simplex virus type 2 (HSV-2) infection increases human immunodeficiency virus acquisition. We hypothesized that HSV-2 infection might also predispose individuals to acquire other common sexually transmitted infections (STIs).

Methods: We studied the association between prevalent HSV-2 infection and STI incidence in a prospective, randomized trial of periodic STI therapy among Kenyan female sex workers.

Sustained changes in sexual behavior by female sex workers after completion of a randomized HIV prevention trial.

Introduction: Behavioral interventions in female sex workers (FSWs) are associated with changes in sexual behavior and reduced rates of sexually transmitted infections (STIs) and HIV We examined the sustainability of such interventions.

Methods: HIV-uninfected Kenyan FSWs were enrolled in a clinical trial that provided free male condoms, community and clinic-based counseling, and STI management. After trial completion, scaled-back community-based resources remained in place.

Relationship between markers of HIV-1 disease progression and serum beta-carotene concentrations in Kenyan women.

Observational studies have suggested that low serum beta-carotene concentrations may influence HIV-1 disease progression. However, randomized trials have not demonstrated beneficial effects of beta-carotene supplementation. To understand this discrepancy, we conducted a cross-sectional study among 400 HIV-1-seropositive women in Mombasa, Kenya, to correlate serum beta-carotene concentrations with several measures of HIV-1 disease severity.

Studies of a prophylactic HIV-1 vaccine candidate based on modified vaccinia virus Ankara (MVA) with and without DNA priming: effects of dosage and route on safety and immunogenicity.

Background: Two parallel studies evaluated safety and immunogenicity of a prophylactic HIV-1 vaccine in 192 HIV-seronegative, low-risk volunteers. Modified vaccinia virus Ankara (MVA) and plasmid DNA (pTHr) expressed HIV-1 clade A gag p24 and p17 fused to a string of 25 overlapping CD8+ T cell epitopes (HIVA).

Methods: These studies compared intramuscular, subcutaneous, and intradermal MVA at dosage levels ranging from 5x10(6)-2.

Strong TCR conservation and altered T cell cross-reactivity characterize a B*57-restricted immune response in HIV-1 infection.

HLA-B*57 is associated with slower disease progression to AIDS, and CD8+ T cell responses to B*57-restricted epitopes are thought to contribute to this protective effect. In this study, we evaluate the B*57-restricted p24 KAFSPEVIPMF (KF11) immune response which is immunodominant during chronic infection. Previously, we observed that the KF11 clade variants KGFNPEVIPMF [A2G,S4N] and KAFNPEIIMPF [S4N,V7I], sharing a position 4 mutation, are differentially recognized by KF11-specific T cells.

HIV-1 infection alters the retinol-binding protein:transthyretin ratio even in the absence of the acute phase response.

The ratio of retinol-binding protein (RBP) to transthyretin (TTR) has been proposed as an indirect method with which to assess vitamin A status in the context of inflammation. Few studies have been conducted among adults, and none examined the effect of HIV-1 infection. Our goal was to assess the RBP:TTR ratio among adults, including the effects of HIV-1 and the acute phase response.

Acceptability of human immunodeficiency virus testing in patients with invasive cervical cancer in Kenya.

Invasive cervical cancer (ICC) is common in areas where human immunodeficiency virus (HIV) is also prevalent. Currently, HIV seroprevalence as well as acceptability of HIV testing in ICC patients in Kenya is unknown. The objective of this study was to determine the acceptability of HIV testing among patients with ICC.

Identification of a novel HLA B*57 restricted cytotoxic T-lymphocyte epitope within HIV-1 rev.

HLA-B5701 and its related allele B5703 have been shown to be strongly associated with slow HIV-1 disease progression. To elucidate the effect of these alleles fully on disease progression it is essential to identify key HIV-1 epitopes that are restricted by these alleles. Here we describe the identification of a novel HLA-B5701, B5703 restricted epitope within HIV-1 rev, which accounted for up to 25 and 40% of the total cytotoxic T-lymphocyte responses in two patients.

HIV impact on acute morbidity and pelvic tumor control following radiotherapy for cervical cancer.

Objective: To determine the impact of HIV infection on acute morbidity and pelvic tumor control following external beam radiotherapy (EBRT) for cervical cancer.

Method: 218 patients receiving EBRT who also had HIV testing after informed consent was obtained were evaluated. Acute treatment toxicity was documented weekly during treatment and 1 month post-EBRT.

Congenital syphilis in a Nairobi maternity hospital.

Objective: To assess adverse pregnancy outcome associated with maternal syphilis and congenital syphilis rate based on FTA-ABS-19s-IgM.

Design: Descriptive cross-sectional study.

Setting: Pumwani Maternity Hospital (PMH), the largest maternity unit in Nairobi, Kenya.

Comparison of pap smear, visual inspection with acetic acid, human papillomavirus DNA-PCR testing and cervicography.

Objective: To assess the test qualities of four screening methods to detect cervical intra-epithelial neoplasia in an urban African setting.

Method: Six hundred fifty-three women, attending a family planning clinic in Nairobi (Kenya), underwent four concurrent screening methods: pap smear, visual inspection with acetic acid (VIA), PCR for high risk human papillomavirus (HR HPV) and cervicography. The presence of cervical intra-epithelial neoplasia (CIN) was verified by colposcopy or biopsy.

Associations of sexual risk taking among Kenyan female sex workers after enrollment in an HIV-1 prevention trial.

Background: Female sex workers (FSWs) often lack the ability to negotiate safer sex and are at high risk for HIV-1 infection and sexually transmitted infections (STIs).

Methods: Seronegative FSWs were enrolled in an STI/HIV-1 prevention trial in Nairobi, Kenya. Demographics and sexual risk taking were assessed every 3 months.

Female-to-male infectivity of HIV-1 among circumcised and uncircumcised Kenyan men.

Background: A lack of male circumcision has been associated with increased risk of human immunodeficiency virus type 1 (HIV-1) acquisition in a number of studies, but questions remain as to whether confounding by behavioral practices explains these results. The objective of the present study was to model per-sex act probabilities of female-to-male HIV-1 transmission (i.e.

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.

HIV-1 Env-specific cytotoxic T-lymphocyte responses in exposed, uninfected Kenyan sex workers: a prospective analysis.

The prospective significance of HIV-specific cytotoxic T lymphocyte (CTL) responses in highly exposed, persistently seronegative populations is unknown. In 1996-1997 we screened for CTL responses against HIV clade B Env in 39 recently enrolled Kenyan female sex workers, and followed these women prospectively. Annual HIV incidence was 5.