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 1 mg intradermally (id), n = 20, or 3.8 mg 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 (108 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. 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.

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BackgroundSelf-initiation to antiretroviral treatment (ART) exposes the patient to the risk of drug toxicity, poor adherence to treatment, and escalates the development of drug resistance.ObjectivesTo determine the sources of antiretroviral (ARV) drugs by unregistered human immunodeficiency virus (HIV)-infected patients and the extent of ARV self-medication.MethodsSimulated clients were used to investigate availability and ARV dispensing practice in the private pharmacies in Dar Es Salaam, Tanzania. A total of 480 HIV-infected patients qualifying to start ART were interviewed to find out their previous use of ARV drugs prior to visiting the HIV clinics. Venous blood (2 mL) was collected from each patient who indicated not to have used ARVs in the past (n = 450). Blood samples were analyzed for the presence and levels of nevirapine (NVP).ResultsOnly 5.1% (23/451) of pharmacies were found stocking ARVs drugs, among which 4.0% were retail. Drug dispensers in nearly all (15/18) retail pharmacies which stocked ARVs were willing to sell ARVs without prescription. Out of 450 enrolled patients, only 2.7% (12) stated that they had been receiving ARV drugs from HIV clinics but interrupted the ART treatment due to various reasons. From 450 patients, only 10% had quantifiable NVP concentrations in the blood, despite stating in an interview that they had not recently used ARVs.ConclusionPrior use of ARV drugs outside HIV clinics was rare among patients attending those centers. However, the results show that some patients could access and use ARV drugs from private pharmacies without undergoing ART eligibility assessment in HIV clinics.

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