In vitro reactivation of latent HIV-1 by cytostatic bis (thiosemicarbazonate) gold(III) complexes

BACKGROUND : A number of cytostatic agents have been investigated for the ability to reactivate latent viral reservoirs, which is a major prerequisite for the eradication of HIV-1 infection. Two cytostatic bis(thiosemicarbazonate) gold(III) complexes (designated 1 and 2) were tested for this potential in the U1 latency model of HIV-1 infection. METHODS : Cell viability in the presence or absence of 1 and 2 was determined using a tetrazolium dye and evidence of reactivation was assessed by p24 antigen capture following exposure to a latency stimulant, phorbol myristate acetate (PMA) and or test compounds. The latency reactivation mechanism was explored by determining the effect of the complexes on protein kinase C (PKC), histone deacetylases (HDAC) and proinflammatory cytokine production. RESULTS : The CC50 of the complexes in U1 cells were 0.53 ± 0.12 μM for 1 and 1.0 ± 0.4 μM for 2. In the absence of PMA and at non toxic concentrations of 0.2 and 0.5 μM, 1 and 2 significantly (p ≤ 0.02) reactivated virus in U1 cells by 2.7 and 2.3 fold respectively. In comparison, a 2.6 fold increase (p = 0.03) in viral reactivation was observed for hydroxyurea (HU), which was used as a cytostatic and latent HIV reactivation control. Viral reactivation was absent for the complexes during co-stimulation with PMA indicating the lack of an additive effect between the chemicals as well as an absence of inhibition of PMA induced HIV reactivation but for HU inhibition of the stimulant’s activity was observed (p = 0.01). Complex 1 and 2 activated PKC activity by up to 32% (p < 0.05) but no significant inhibition of HDAC was observed. Increases in TNF-α levels suggested that the reactivation of virus by the complexes may have been due to contributions from the latter and the activation of PKC. CONCLUSION : The ethyl group structural difference between 1 and 2 seems to influence bioactivity with lower active concentrations of 1, suggesting that further structural modifications should improve specificity. The cytostatic effect of 1 and 2 and now HIV reactivation from a U1 latency model is consistent with that of the cytostatic agent, HU. These findings suggest that the complexes have a potential dual (cytostatic and reactivation) role in viral “activation/elimination”.AuTEK Biomed (Mintek and Harmony Gold),Technology Innovation Agency (TIA) and the University of Pretoria.http://www.biomedcentral.com/bmcinfectdis/hb201

Interest in the &#x2018;Test and Treat&#x2019; strategy for HIV prevention among men who have sex with men living in Bangkok

Background: The current HIV epidemic in Thailand is primarily driven by new cases among men who have sex with men (MSM). HPTN052 study demonstrated 96% efficacy of immediate antiretroviral therapy (ART) to reduce HIV transmission among serodiscordant heterosexual couples. As a result, universal HIV testing and immediate ART has emerged as a strategy to reduce HIV transmission in certain at-risk populations. The acceptability of this strategy, however, is unknown in MSM. Methods: From August 2011-March 2012, we conducted a cross-sectional study using self-administered questionnaires to assess attitudes towards universal HIV testing and immediate ART among MSM VCT clients in Bangkok. Participants were asked to complete the questionnaires prior to and after knowing their HIV status. The study was approved by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Results: Of 342 MSM, the median age (IQR) was 26 (22&#x2013;31) years, and 34.2% had bachelor&#x0027;s degree or higher. Previous HIV testing was reported by 69.9%, 35.2% of which had HIV testing annually. The most common reasons for previous HIV testing included perceived risk behaviors (63.6%), annual health checkup (26.4%), and partner&#x0027;s request (13.8%). Prior to receiving pre-test counseling, 74.4% expressed interest to get regular HIV testing. Health benefits from testing (59.6%), free testing (36.5%), and speedy service (35.7%) were the most common persuasive reasons to come for regular HIV testing. Longevity (73.1%) and prevention of HIV transmission to others (58.4%) were reasons for interest in immediate ART (if tested positive) program while costs (37.0%) and life-long burden (36.7%) were cited as main barriers. Among MSM who tested HIV-positive (n=45, 13.2%), the interest to participate in immediate ART program was very high both before and after knowing their HIV status (86.7% vs 93.3%, p=0.371). Among HIV-negative MSM, the interest to participate in regular HIV testing program significantly increased after knowing HIV status (83.4% vs 77.0%, p&#x3C;0.001). Conclusions: MSM in Bangkok showed high level of interest in the &#x201C;Test and Treat&#x201D; strategy for HIV prevention. Knowing one&#x0027;s HIV status affected the interest to access regular HIV testing program