The human immunodeficiency virus (HIV) vaccine is urgently needed to curtail the global AIDS epidemic. Here, we report the findings from the Phase I clinical trial of a candidate multigene HIV-1 clade A DNA vaccine and demonstrate the induction of HIV-1-specific immune responses.Three groups of trial participants (21 healthy HIV-1-negative adult volunteers) were vaccinated four times with one of three different doses of DNA (0.25, 0.5 or 1.0 mg) administered intramuscularly. Vaccine-induced immune responses were measured by extensively validated methods, including ELISA, intracellular cytokine staining (ICS), IFNγ enzyme immunospot (ELISpot) assay and lymphocyte proliferation assay.We found that our DNA vaccine was safe and well-tolerated at three used doses. Altogether, T-cell immune responses were elicited in all of 21 participants. We observed the increase in lymphocyte proliferation after fourth immunization that can show the advantage of fourfold against triple immunization. The frequency of detection positive cytokine responses decreases with increasing the vaccine dose. The humoral responses were induced in 5 people (24%). We didn't observe any correlation between the antibody production and the DNA-4 vaccine doses.We also found the important correlation with our results obtained for the HIV specific immune responses in exposed seronegative individuals, i.e. TNFa production in immunized group.Our findings of 100% immune reactivity of trial participants and the correlation of TNFa production with that in ESN individuals, may be promising indications for the possible efficacy of our candidate DNA vaccine.

Background: Untreated opioid addiction in persons with HIV is associated with poor outcome. Slow release, long-acting, implantable naltrexone may improve outcomes. Methods: We conducted a 48-week outcome study beween July 2011 and April 2015 of opioid addicted males and females starting antiretroviral treatment (ART) for HIV whose viral loadwas ≥1000 copies per mL and were seeking treatment at HIV and Narcology programs in St. Petersburg and the surrounding Leningrad Region, Russian Federation. We stratified participants according to gender, viral load (VL) and CD4 cells per μL, and randomized them to addiction treatment with a naltrexone implant and oral naltrexone placebo (NI), or oral naltrexone and placebo implant (ON). The primary outcome was plasma viral load of ≤400 copies per mL at 24 and 48 weeks. We included all randomized participants in outcome analyses. Treatment staff was blinded to group assignment. The study is complete and registered at ClinicalTrials.gov, NCT01101815 Findings: 238 potential subjects were screened, 35 excluded for not meeting inclusion criteria, 3 declined to participate and 200 were randomized. There was no difference between NI and ON in the number of participants with VL≤400 copies per mL at week 24 (38 [38%] vs 35 [35%] p=0•77) but more NI than ON participants had a VL≤400 copies per mL at week 48 (66 [66%] vs 50 [50%] RR: 1•32 [95% CI: 1•04−1•68] p=0•0451). There were seven serious adverse events: three deaths in NI (one heart disease, one trauma, one AIDS), and four in ON (two overdoses, one pancreatic cancer, one AIDS). The overdose deaths occurred 9-10 months after the last naltrexone dose. Interpretation: The longer the blockade, the more protection from missed doses and the impulsive behaviors that lead to relapse and poor, even fatal outcomes. Commercial development of implants could result in a meaningful addition to current addiction treatment options.

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