Safety and Immunogenicity Study of Multiclade HIV-1 Adenoviral Vector Vaccine Alone or as Boost following a Multiclade HIV-1 DNA Vaccine in Africa

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.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. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-γ) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-γ ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone.The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was well-tolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints.ClinicalTrials.gov NCT00124007

Health seeking and sexual behaviour among primary healthcare patients in Nairobi, Kenya.

Background: Health-seeking and sexual behaviors are important elements in the control of sexually transmitted infections (STIs). Goal: To examine patterns of health-seeking behavior and related sexual behavior relevant to improved prevention and care among patients attending primary healthcare (PHC) clinics. Study Design: A questionnaire covering social, demographic, and healthcare-seeking and sexual behavior information was administered to 555 patients attending three primary healthcare clinics in low socioeconomic areas of Nairobi, Kenya. Results: Women\u27s knowledge about health in general and STIs in particular was poor. A major gender difference in delay of health seeking for STIs was observed (5 days for men versus 14 days for women). Significantly more men than women reported a history of STIs (68% versus 47%; P = 0.04). Men reported more extramarital affairs (17% versus 8%; P \u3c 0.001). A high prevalence of gonorrhea (3%) and chlamydia (6%) was found in this population, with no difference between the genders. The urine dipstick was ineffective for the detection of these STIs. Conclusions: There is a need for better understanding of behavioral factors, as well as gender and social aspects of health care. Health education and health promotion in these areas should be strengthened. Improved screening tests are needed for the detection of STI

Pattern of Sexually Transmitted Diseases and Risk Factors Among Women Attending an STD Referral Clinic in Nairobi, Kenya

Background: In Kenya, sexually transmitted disease (STD) clinics care for large numbers of patients with STD-related signs and symptoms. Yet, the etiologic fraction of the different STD pathogens remains to be determined, particularly in women. Goal: The aim of the study was to determine the prevalence of STDs and of cervical dysplasia and their risk markers among women attending the STD clinic in Nairobi. Study Design: A cross-section of women were interviewed and examined; samples were taken. Results: The mean age of 520 women was 26 years, 54% had a stable relationship, 38% were pregnant, 47% had ever used condoms (1% as a method of contraception), 11% reported multiple partners in the previous 3 months, and 32% had a history of STDs. The prevalence of STDs was 29% for HIV type 1, 35% for candidiasis, 25% for trichomoniasis, 16% for bacterial vaginosis, 6% for gonorrhea, 4% for chlamydia, 6% for a positive syphilis serology, 6% for genital warts, 12% for genital ulcers, and 13% for cervical dysplasia. Factors related to sexual behavior, especially the number of sex partners, were associated with several STDs. Gonorrhea, bacterial vaginosis, cervical dysplasia , and genital warts or ulcers were independently associated with HIV infection. Partners of circumcised men had less-prevalent HIV infection. Conclusion: Most women reported low-risk sexual behavior and were likely to be infected by their regular partner. HIV and STD prevention campaigns will not have a significant impact if the transmission between partners is not addressed

Vulnerability of women in an African setting: lessons for mother-to-child HIV transmission prevention programmes

After discussing advantages and risks, only a third of the 290 HIV-infected women included in an intervention study to reduce mother-to-child transmission of HIV in Mombasa, Kenya, informed their partners of their results. Despite careful counselling, 10% subsequently experienced violence or disruption of their relationship. To increase the uptake of interventions to reduce perinatal HIV transmission safely, we recommend the involvement of partners in HIV testing. In addition, the counselling of women has to address methods and skills to deal with violence

Impact of HIV infection on invasive cervical cancer in Kenyan women

Objectives: To determine the association between invasive cervical cancer (ICC) and HIV infection in Kenyan women. Study design: Case-control, with ICC patients as cases, and women with uterine fibroids as controls. Methods: Medical and socio-demographic data were collected from 367 ICC patients, and 226 women with fibroids. After informed consent, HIV testing was done. Results: ICC patients were older than fibroid patients (48 versus 41 years; P \u3c 0.001), with an HIV seroprevalence of 15% and 12% respectively (P \u3e 0.05). However, cases younger than 35 years were 2.6-times more likely to be HIV positive than controls of similar age [35% versus 17%; odds ratio (OR), 2.6; P = 0.043]. ICC HIV-seropositive patients were, on average, 10 years younger than HIV-seronegative patients (40 versus 50 years; P \u3c 0.001). Eighty per cent of HIV-seropositive and 77% of HIV-seronegative ICC patients were in FIGO stage IIb or above. However, the odds of having poorly differentiated tumours was three times higher for HIV-seropositive than for HIV-seronegative ICC patients (77% versus 52%; OR, 3.1; P = 0.038) after adjusting for histological cell type and clinical stage. Mean CD4 cell count was 833 × 106 cells/l in ICC and 1025 × 106 cells/l in fibroid patients (P = 0.001). Conclusion: Young women with ICC were more often HIV infected than women with fibroids of the same age groups. HIV infection was associated with poor histological differentiation of the tumours. These findings suggest an accelerated clinical progression of premalignant cervical lesions to ICC in HIV-infected women

Exposure to HIV-1 during delivery and mother-to-child transmission.

Background The correlation between the presence of HIV-1 in maternal cervico-vaginal secretions and in the infant\u27s oro-pharyngal secretions at birth, and mother-to-child HIV transmission (MTCT) were examined to obtain a better understanding of its mechanism. Methods Women without medical and obstetrical complications, living within a reasonable distance of the government hospital in Mombasa, Kenya, were recruited after informed consent. Maternal and infant characteristics were collected. Polymerase chain reaction was used to detect HIV-1 in cervico-vaginal and oro-pharyngal secretions. Infants were tested for HIV-1 by polymerase chain reaction within 48 h and at 6 weeks after delivery. Results Between April 1998 and April 1999, 228 woman–infant pairs were included in the study. HIV-1 DNA in cervico-vaginal secretions was independently associated with HIV-1 maternal viral load and with infant birth-weight, whereas HIV-1 RNA was associated with maternal viral load and maternal age. HIV-1 DNA in the oro-pharyngal secretions was also independently associated with maternal viral load. MTCT rate at the age of 6 weeks was 23.6%. Intrapartum and early postpartum HIV transmission was independently associated with maternal viral load [adjusted odds ratio (OR), 1.6; 95% confidence interval (CI),1.0–2.7], detection of HIV-1 RNA in cervico-vaginal secretions (adjusted OR, 3.2; 95% CI, 1.5–7.3) and of HIV-1 DNA in oro-pharyngal secretions (adjusted OR, 3.2; 95% CI, 1.1–9.0). Discussion As far as is known, this is the first study showing that infant exposure to HIV-1 in the birth canal and the presence of HIV-infected cells in the infant\u27s oro-pharyngal cavity are independently associated with intrapartum and early postpartum MTCT. It supports the hypothesis that MTCT could occur through the oral route

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. Predictors of reduced risk taking were defined using multivariate logistic regression. Results: Four hundred sixty-six FSWs were enrolled and followed for just over 2 years each. A spectrum of sex work was apparent: FSWs working in night clubs were younger, charged more for sex, and used condoms more frequently; FSWs working from home were older, charged less, and used condoms the least; and those working in bars were intermediate. Increases in reported condom use were most significant and sustained for FSWs working from home and charging less for sex and were poorly maintained for bar-based FSWs. Self-reported lower condom use, higher client numbers, and alcohol use were associated with higher STI rates. Conclusions: Home-based FSWs and those charging less for sex used condoms the least at baseline but showed the greatest and most sustained improvements over time. Potential response heterogeneity in FSW subgroups should be considered in the design of HIV-1 prevention programs