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Objectives Although antiretroviral therapy (ART) prolongs life and reduces infectiousness, in some contexts, it has been associated with increased sexual risk taking. Design Retrospective case–control study. Setting Nairobi-based dedicated female sex worker (FSW) clinic. Participants HIV-infected FSWs before and after ART initiation (n=62); HIV-infected and -uninfected control FSWs not starting ART during the same follow-up period (n=40). Intervention Initiation of ART. Primary outcome measures Self-reported condom use, client numbers and sexually transmitted infection incidence over the study period (before and after ART initiation in cases). Results Sexual risk-taking behaviour with casual clients did not increase after ART initiation; condom use increased and sexually transmitted infection incidence decreased in both cases and controls, likely due to successful cohort-wide HIV prevention efforts. Conclusions ART provision was not associated with increases in unsafe sex in this FSW population., Article summary Article focus Impact of starting ART on sexual risk-taking behaviour in FSWs, which could have an important impact on HIV transmission to clients. Key messages ART initiation was not associated with increased risk taking or sexually transmitted infection incidence. Both of these declined over time, most likely as a result of risk reduction counselling. Strengths and limitations of this study Strengths include a relevant population, longitudinal follow-up and inclusion of biological measures of risk taking (sexually transmitted infection incidence). Limitations include relatively small study groups and limited sampling time points.

BackgroundWe 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 findingsVolunteers 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.Conclusions/significanceThe 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.Trial registrationClinicalTrials.gov NCT00124007.

Highlights • MVA.HIVA vaccine was tested for the first time in HIV-1-exposed infants in Africa. • PedVacc 002 had 99% retention of infants over 48 weeks of follow-up. • MVA.HIVA was safe, but not sufficiently immunogenic. • MVA.HVA did not interfere with routine childhood vaccines except for induction of HBV antibodies. • MVA is well suited as a vaccine vector for infants under 1 year of age., Background A safe, effective vaccine for breastfeeding infants born to HIV-1-positive mothers could complement antiretroviral therapy (ART) for prevention of mother-to-child transmission of HIV-1. To date, only a few HIV-1 vaccine candidates have been tested in infants. Trial design A phase I/II randomized controlled trial PedVacc 002 was conducted to determine the safety and immunogenicity of a single, low dose of MVA.HIVA vaccine delivered intramuscularly to healthy 20-week-old infants born to HIV-1-positive mothers in Nairobi, Kenya. Methods Pregnant HIV-1-positive women in the 2nd/3rd trimester of gestation were enrolled, provided with ART and self-selected their infant-feeding modality. Infants received nevirapine and cotrimoxazole prophylaxis. At 20 weeks of age, eligible HIV-1-negative infants were randomized to vaccine versus no-treatment arms and followed to 48 weeks of age for assessments of vaccine safety, HIV-1-specific T-cell responses and antibodies to routine childhood vaccines. Results Between February and November 2010, 182 mothers were screened, 104 were eligible and followed on ART during pregnancy/postpartum, of whom 73 had eligible infants at 20 weeks postpartum. Thirty-six infants were randomized to vaccine and 37 to no treatment. Eighty-four percent of infants breastfed, and retention at 48 weeks was 99%. Adverse events were rare and similar between the two arms. HIV-1-specific T-cell frequencies in interferon-γ ELISPOT assay were transiently higher in the MVA.HIVA arm (p = 0.002), but not above the threshold for a positive assay. Protective antibody levels were adequate and similar between arms for all routine childhood vaccines except HBV, where 71% of MVA.HIVA subjects compared to 92% of control subjects were protected (p = 0.05). Conclusions This trial tested for the first time an MVA-vectored candidate HIV-1 vaccine in HIV-1-exposed infants in Africa, demonstrating trial feasibility and vaccine safety, low immunogenicity, and compatibility with routine childhood vaccinations. These results are reassuring for use of the MVA vector in more potent prime-boost regimens.

Background European and Developing Countries Clinical Trials Partnership (EDCTP) was founded in 2003 by the European Parliament and Council. It is a partnership of 14 European Union (EU) member states, Norway, Switzerland, and Developing Countries, formed to fund acceleration of new clinical trial interventions to fight the human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), malaria and tuberculosis (TB) in the sub-Saharan African region. EDCTP seeks to be synergistic with other funding bodies supporting research on these diseases. Methods EDCTP promotes collaborative research supported by multiple funding agencies and harnesses networking expertise across different African and European countries. EDCTP is different from other similar initiatives. The organisation of EDCTP blends important aspects of partnership that includes ownership, sustainability and responds to demand-driven research. The Developing Countries Coordinating Committee (DCCC); a team of independent scientists and representatives of regional health bodies from sub-Saharan Africa provides advice to the partnership. Thus EDCTP reflects a true partnership and the active involvement and contribution of these African scientists ensures joint ownership of the EDCTP programme with European counterparts. Results The following have been the major achievements of the EDCTP initiative since its formation in 2003; i) increase in the number of participating African countries from two to 26 in 2008 ii) the cumulative amount of funds spent on EDCTP projects has reached € 150 m, iii) the cumulative number of clinical trials approved has reached 40 and iv) there has been a significant increase number and diversity in capacity building activities. Conclusion While we recognise that EDCTP faced enormous challenges in its first few years of existence, the strong involvement of African scientists and its new initiatives such as unconditional funding to regional networks of excellence in sub-Saharan Africa is envisaged to lead to a sustainable programme. Current data shows that the number of projects supported by EDCTP is increasing. DCCC proposes that this success story of true partnership should be used as model by partners involved in the fight against other infectious diseases of public health importance in the region.

Background: Changes in susceptibility patterns of bacterial pathogens isolated from urinary tract infections emphasize the need for regional surveillance to generate information that can be used in management of patients. Knowledge on the current status of antimicrobial resistance in uropathogens, and the prevalence of expanding spectrum beta-lactamases (ESBLs) in the isolates will guide policy formulations and encourage prudent use of antimicrobials.Objectives: To identify bacterial pathogens causing UTI and determine the association between the pathogens isolated from patients attending KNH. Determine antimicrobial susceptibility patterns of the UTI pathogens and the prevalence of ESBL in the isolated pathogens.Design: Laboratory-based study.Setting: Department of Medical Microbiology University of Nairobi and Kenyatta National Hospital microbiology laboratory, Nairobi, Kenya.Subjects: Nine hundred and forty eight patients presenting directly to the Kenyatta National Hospital’s diagnostic laboratory. Patients were only classified as in-patients if at the time of specimen collection they were being admitted to one of KNH wards.Results: Out of the 948 urine samples processed, 189 in-patients and 37 out-patients samples had significant bacterial growth. The uropathogens identified from inpatient specimens were Escherichia coli (56), Klebsiellapneumoniae (33), Enterococcus spp. (34) and Entrobacter (16) making up 30%, 18%, 18% and 9% respectively. ESBL isolates were found to be resistant to the locally administered antibiotics; Augmentin (37%), Levofloxacin (37%), Cefoperazone (37%), Ampicillin (39%), Doxycyline (41%), Gentamicin (30%) and Nalidixic Acid (38%).Conclusion: The increased prevalence of multidrug resistant ESBL pathogens poses challenges for healthcare providers at KNH and signifies the need for new approach to treat UTI. It would be prudent for laboratories to include specialised tests for detection of ESBL producing pathogens from isolates obtained from in-patients. Further studies on the mechanisms and pathways utilised by these bacteria to cause UTI will highlight other avenues in patient management.

Background Pathological changes due to infection with Schistosoma haematobium include cytokine-mediated urinary tract inflammation. The involved cytokines may be excreted in urine and their presence in urine may therefore reflect S. haematobium-related urinary tract pathology. The present study, for the first time, reports on the relationship between selected cytokines in urine and infection with S. haematobium in children from an area highly affected by this parasite. Methods Children aged 5–12 years from two primary schools in Tana Delta District of Kenya were examined for S. haematobium eggs using urine filtration technique, for haematuria using dipstix and for eosinophil cationic protein (ECP), IL-6, IFN- γ, TNF-α and IL-10 levels using ELISA, and for S. haematobium-related urinary tract pathology using ultrasonography. In addition, venous blood was examined for serum IL-6, IFN- γ, TNF-α and IL-10 levels using ELISA. Results There was no significant correlation between urinary and serum levels of IL-6, IFN- γ, TNF-α or IL-10. There was no significant difference in geometric mean intensity (GMI) in any of the serum cytokines, or in urinary TNF-α or IFN-γ, between children with light and heavy S. haematobium infections. However, children with heavy S. haematobium infections had significantly higher GMI of urinary IL-6 (p

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. Results: Of the 6,415 adults screened for antibodies to HIV at Kenyatta National Hospital VCT Centre between July 2002 and February 2003, 728 tested positive in the two HIV screening tests used at the center, indicating a prevalence of 11%. Of these seropositive cases, 355 consented to participate in the study. Using STARHS, 34 (9.6%) of the plasma samples were classified as being from individuals with recent infection (within 170 days), giving an annual estimated HIV-1 incidence in this population of 1.3 infections per 100 person-years with a 95% CI of 0.872–1.728%. Young adults had a higher rate of new infection than older adults. Young females were infected much earlier in life, with a peak age of new infections of 26 years, versus. 31 years for young males. Conclusion: This study confirms our hypothesis that STARHS or Detuned assay can be used to determine HIV incidence in this population. The HIV high risk groups as identified by this study are young women between ages 16 to 26 years old and men between ages 45 to 55 years of age.

Objectives: To determine the prevalence, clinical features, risk factors and outcomes associated with cryptococcal meningitis (CM) in human immunodeficiency virus (HIV) positive patients at two referral hospitals in Nairobi, Kenya.Design: Prospective, observational study.Setting: Kenyatta National Hospital (KNH) and Mbagathi District Hospital (MDH), Nairobi, KenyaSubjects: Three hundred and forty HIV patients presenting with suspected CM.Results: Of three hundred and forty suspected CM patients, 111 (33%) were diagnosed with CM by CrAg. Among CM patients, in-hospital mortality was 36% (38/106), median age was 35 years (range, 19-60 years) and median CD4 count was 41 cells/μL (n=89, range 2-720 cells/μL). Common clinical manifestations among CM patients included headache 103 (93%), neck stiffness 76 (69%) and weight loss 53 (48%). Factors independently associated with CM were male sex, headache, blurred vision and previous antifungal drug use. Night sweats and current use of anti-retroviral therapy were associated with reduced risk for CM.Conclusions: There is a high prevalence of CM and CM-associated mortality in HIV patients at KNH and MDH despite treatment with antifungal and anti-retroviral drugs. This study demonstrates the need to address the existing inadequacies of CM patient outcomes in Kenya.