In contrast to the results mentioned above has been published a randomized, double-blind, placebo-controlled trial performed on 83 patients to which 400 mg HCQ (n = 42) or placebo (n = 41) were administered for 48 weeks. All patients were naïve to HAART or had stopped this therapy 22 months before the trial began; 17 subjects in the HCQ group and 8 in the placebo group interrupted study medication before the 48th week. At the end of treatment, in the HCQ group, compared to placebo, patients showed a reduction in total CD4 cell count and a significant viral load increased from the 12th week above baseline [24]. Hence, based on these results, HCQ did not decrease immune activation in patients with chronic HIV infection who were naïve to HAART, as there was an increase in HIV viral replication and a negative effect on CD4+ cell counts. In light of these results, there was the need to consider that the first two described clinical trials, which reported the antiviral effect of HCQ, were on short-term treatments (8 or 16 weeks) and that they used an HCQ dosage of 800 mg/day [17,18]. In contrast, the latter used only 400 mg/day [24], corresponding to the maximum recommended dose for long-time use. Besides, the latter study also enrolled more patients than the other studies, and unlike the trial of Piconi et al. [23], which described significative effects in reducing immune activation after HCQ administration, was conducted in the absence of antiretroviral treatments [24]. Therefore, further clinical trials involving a larger number of subjects would be necessary to assess the real antiviral activity of HCQ in monotherapy and synergy with antiretrovirals drugs.