Candida Moshiro

Broad and potent immune responses to a low dose intradermal HIV-1 DNA boosted with HIV-1 recombinant MVA among healthy adults in Tanzania☆☆☆

BACKGROUND We conducted a phase I/II randomized placebo-controlled trial with the aim of exploring whether priming with a low intradermal dose of a multiclade, multigene HIV-1 DNA vaccine could improve the immunogenicity of the same vaccine given intramuscularly prior to boosting with a heterologous HIV-1 MVA among healthy adults in Dar es Salaam, Tanzania. METHODS Sixty HIV-uninfected volunteers were randomized to receive DNA plasmid vaccine 1mg intradermally (id), n=20, or 3.8mg intramuscularly (im), n=20, or placebo, n=20, using a needle-free injection device. DNA plasmids encoding HIV-1 genes gp160 subtype A, B, C; rev B; p17/p24 gag A, B and Rtmut B were given at weeks 0, 4 and 12. Recombinant MVA (10(8)pfu) expressing HIV-1 Env, Gag, Pol of CRF01_AE or placebo was administered im at month 9 and 21. RESULTS The vaccines were well tolerated. Two weeks after the third HIV-DNA injection, 22/38 (58%) vaccinees had IFN-γ ELISpot responses to Gag. Two weeks after the first HIV-MVA boost all 35 (100%) vaccinees responded to Gag and 31 (89%) to Env. Two to four weeks after the second HIV-MVA boost, 28/29 (97%) vaccinees had IFN-γ ELISpot responses, 27 (93%) to Gag and 23 (79%) to Env. The id-primed recipients had significantly higher responses to Env than im recipients. Intracellular cytokine staining for Gag-specific IFN-γ/IL-2 production showed both CD8(+) and CD4(+) T cell responses. All vaccinees had HIV-specific lymphoproliferative responses. All vaccinees reacted in diagnostic HIV serological tests and 26/29 (90%) had antibodies against gp160 after the second HIV-MVA boost. Furthermore, while all of 29 vaccinee sera were negative for neutralizing antibodies against clade B, C and CRF01_AE pseudoviruses in the TZM-bl neutralization assay, in a PBMC assay, the response rate ranged from 31% to 83% positives, depending upon the clade B or CRF01_AE virus tested. CONCLUSIONS This vaccine approach is safe and highly immunogenic. Low dose, id HIV-DNA priming elicited higher and broader cell-mediated immune responses to Env after HIV-MVA boost compared to a higher HIV-DNA priming dose given im. Three HIV-DNA priming immunizations followed by two HIV-MVA boosts efficiently induced Env-antibody responses.

Risky sexual practices among youth attending a sexually transmitted infection clinic in Dar es Salaam, Tanzania

BackgroundYouth have been reported to be at a higher risk of acquiring STIs with significant adverse health and social consequences. Knowledge on the prevailing risky practices is an essential tool to guide preventive strategies.MethodsYouth aged between 18 and 25 years attending an STI clinic were recruited. Social, sexual and demographic characteristics were elicited using a structured standard questionnaire. Blood samples were tested for syphilis and HIV infections. Urethral, high vaginal and cervical swabs were screened for common STI agents.ResultsA total of 304 youth were studied with mean age of 21.5 and 20.3 years for males and females respectively. 63.5% of youth were seeking STI care. The mean age of coitache was 16.4 and 16.2 years for males and females respectively. The first sexual partner was significantly older in females compared to male youth (23.0 vs 16.8 years) (p < 0.01). 93.2% of male youth reported more than one sexual lifetime partner compared to 63.0% of the females. Only 50% of males compared to 43% of females had ever used a condom and fewer than 8.3% of female youth used other contraceptive methods. 27.1% of pregnancies were unplanned and 60% of abortions were induced. 42.0% of female youth had received gifts/money for sexual favours. The HIV prevalence was 15.3% and 7.5% for females and males respectively. The prevalence of other STIs was relatively low. Among male youth, use of alcohol or illicit drugs was associated with increased risk of HIV infection. However, the age of sexual initiation, number of sexual partners or the age of the first sexual partner were not associated with increased risk of being HIV infected.ConclusionMost female youth seen at the STI clinic had their first sexual intercourse with older males. Youth were engaging in high risk unprotected sexual practices which were predisposing them to STIs and unplanned pregnancies. There is a great need to establish more youth-friendly reproductive health clinics, encourage consistent and correct use of condoms, delay in sexual debut and avoid older sexual partners in females.

Priming with a Simplified Intradermal HIV-1 DNA Vaccine Regimen followed by Boosting with Recombinant HIV-1 MVA Vaccine Is Safe and Immunogenic: A Phase IIa Randomized Clinical Trial

Background Intradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools. Methods In this phase IIa, randomized trial, priming was performed using 5 injections of HIV-DNA, 1000 μg total dose, (3 Env and 2 Gag encoding plasmids) compared to two “simplified” regimens of 2 injections of HIV-DNA, 600 μg total dose, of Env- and Gag-encoding plasmid pools with each pool either administered separately or combined. HIV-DNA immunizations were given intradermally at weeks 0, 4, and 12. Boosting was performed intramuscularly with 108 pfu HIV-MVA at weeks 30 and 46. Results 129 healthy Tanzanian participants were enrolled. There were no differences in adverse events between the groups. The proportion of IFN-γ ELISpot responders to Gag and/or Env peptides after the second HIV-MVA boost did not differ significantly between the groups primed with 2 injections of combined HIV-DNA pools, 2 injections with separated pools, and 5 injections with separated pools (90%, 97% and 97%). There were no significant differences in the magnitude of Gag and/or Env IFN-γ ELISpot responses, in CD4+ and CD8+ T cell responses measured as IFN-γ/IL-2 production by intracellular cytokine staining (ICS) or in response rates and median titers for binding antibodies to Env gp160 between study groups. Conclusions A simplified intradermal vaccination regimen with 2 injections of a total of 600 μg with combined HIV-DNA plasmids primed cellular responses as efficiently as the standard regimen of 5 injections of a total of 1000 μg with separated plasmid pools after boosting twice with HIV-MVA. Trial Registration World Health Organization International Clinical Trials Registry Platform PACTR2010050002122368

Primary antimicrobial resistance among Mycobacterium tuberculosis isolates from HIV seropositive and HIV seronegative patients in Dar es Salaam Tanzania

BackgroundThe United Republic of Tanzania is one of the 22 high M. tuberculosis burden countries. Data collected between 2002 and 2007 indicate that the global prevalence of drug-resistant M. tuberculosis including MDR vary greatly. The varied drug-resistance patterns make continuous surveillance of drug resistance an essential component of tuberculosis control program.FindingsM. tuberculosis isolates were obtained from consenting adult tuberculosis patients involved in a placebo-controlled study to evaluate the efficacy of multivitamin supplements on response to anti-Tb treatment in Dar es Salaam, Tanzania. Antimicrobial susceptibility testing was done on four antimicrobial agents namely streptomycin, isoniazid, ethambutol and rifampicin. HIV testing and CD4+ T lymphocytes enumeration were also done. A total of 280 M. tuberculosis isolates from 191 (68%) males and 89 (32%) female patients with no previous history of anti-tuberculosis treatment exceeding 4 weeks in the previous 12 months were tested. Among these, 133 (47%) patients were HIV seropositive. Fourteen (5.0%) isolates were resistant to any of the anti-tuberculosis drugs. The prevalence of primary resistance was 5.0%, 0.7%, 0.4% and 0% for isoniazid, streptomycin, rifampicin and ethambutol respectively. One isolate (0.4%) was MDR, with resistance to isoniazid, streptomycin and rifampicin.ConclusionM. Tb primary resistance rate in a selected population in Dar es Salaam Tanzania is low and efforts should be undertaken to support the Tuberculosis program.

P14-14 LB. A low dose of multigene, multiclade HIV DNA given intradermally induces strong and broad immune responses after boosting with heterologous HIV MVA

Open Access Poster presentation P14-14 LB. A low dose of multigene, multiclade HIV DNA given intradermally induces strong and broad immune responses after boosting with heterologous HIV MVA M Bakari*1, S Aboud1, C Nilsson2, J Francis1, D Buma3, C Moshiro1, EA Aris3, E Lyamuya1, M Janabi3, J Mbwana1, L Mwanyika4, R Stout5, B Hejdeman6, A Brave2, M Robb7, M Marovich7, N Michael7, P Earl8, B Moss8, B Wahren2, G Biberfeld2, K Pallangyo1, F Mhalu1 and E Sandstrom6

Experiences on recruitment and retention of volunteers in the first HIV vaccine trial in Dar es Salam, Tanzania - the phase I/II HIVIS 03 trial

BackgroundEventual control of HIV/AIDS is believed to be ultimately dependent on a safe, effective and affordable vaccine. Participation of sub-Saharan Africa in the conduct of HIV trials is crucial as this region still experiences high HIV incidences. We describe the experience of recruiting and retaining volunteers in the first HIV vaccine trial (HIVIS03) in Tanzania.MethodsIn this trial enrolled volunteers from amongst Police Officers (POs) in Dar es Salaam were primed with HIV-1 DNA vaccine at months 0, 1 and 3; and boosted with HIV-1 MVA vaccine at months 9 and 21. A stepwise education provision/sensitization approach was employed to eventual recruitment. Having identified a “core” group of POs keen on HIV prevention activities, those interested to participate in the vaccine trial were invited for a first screening session that comprised of provision of detailed study information and medical evaluation. In the second screening session results of the initial assessment were provided and those eligible were assessed for willingness to participate (WTP). Those willing were consented and eventually randomized into the trial having met the eligibility criteria. Voluntary participation was emphasized throughout.ResultsOut of 408 POs who formed the core group, 364 (89.0%) attended the educational sessions. 263 out of 364 (72.2%) indicated willingness to participate in the HIV vaccine trial. 98% of those indicating WTP attended the pre-screening workshops. 220 (85.0%) indicated willingness to undergo first screening and 177 POs attended for initial screenings, of whom 162 (91.5%) underwent both clinical and laboratory screenings. 119 volunteers (73.5%) were eligible for the study. 79 were randomized into the trial, while 19 did not turn up, the major reason being partner/family advice. 60 volunteers including 15 females were recruited during a one-year period. All participated in the planned progress updates workshops. Retention into the schedule was: 98% for the 3 DNA/placebo vaccinations, while it was 83% and 73% for the first and second MVA/placebo vaccinations respectively.ConclusionIn this first HIV vaccine trial in Tanzania, we successfully recruited the volunteers and there was no significant loss to follow up. Close contact and updates on study progress facilitated the observed retention rates.Trial registration numbersISRCTN90053831 ISRNCT01132976 and ATMR2009040001075080

Priming with a “simplified regimen” of HIV-1 DNA vaccine is as good as a “standard regimen” when boosted with heterologous HIV-1 MVA vaccine

Priming with a “simplified regimen” of HIV-1 DNA vaccine is as good as a “standard regimen” when boosted with heterologous HIV-1 MVA vaccine P Munseri, A Kroidl, C Nilsson, C Moshiro, S Aboud, A Joachim, C Geldmacher, E Aris, D Buma, E Lyamuya, F Gotch, K Godoy-Ramirez, K Pallangyo, L Maboko, M Marovich, M Robb, M Hoelscher, M Janabi, P Mann, S Joseph, S Mfinanga, W Stoehr, F Mhalu, B Wahren, G Biberfeld, S McCormack, E Sandstrom, M Bakari

Prevalence and risk factors for skin diseases among antiretroviral-naïve HIV-infected pregnant women in Dar es Salaam, Tanzania.

Reduced cell‐mediated immunity associated with pregnancy may cause a flaring or exacerbation of some skin conditions. Little is known about the magnitude of and risk factors for skin diseases among human immunodeficiency virus (HIV)‐infected antiretroviral therapy‐naïve pregnant women.