Highly active antiretroviral therapy (HAART) was recently associated with disturbance of lipid metabolism, fat mass distribution and insulin resistance, known to be partly regulated by steroid hormones. Nevertheless, complementary or adjunctive wide used of dehydroepiandrosterone (DHEA) in fully suppressed HIV patients appeared to have no beneficial antiviral, immuno modulatory, hormonal or body composition effects. Herein, we tested in vivo safety and efficacy of IM28, a potent analog of DHEA, on volunteers HIV positive patients from Gabon, randomly organized as followed: IM28 alone (15 patients + 30 healthy individuals), IM28+HAART (150 patients), HAART alone (13 patients) and DHEA+HAART (23 patients). All patients were evaluated three times: M0 (pre-treatment with IM28), M1 (after six months of treatment with IM28) and M2 (after 12 months of treatment with IM28). No noticeable side effects were observed for IM28 as evaluated by measuring hepatic, cardiac, renal functions and body weight progression. Compared to HAART therapy, combinations DHEA+HAART, IM28+HAART or IM28, quickly rescued patients from anxiety, restored their appetite and normalized their body weight. However, only patients receiving IM28 alone or in combination with HAART showed normalization of body temperatures and increase in the levels of CD4 lymphocytes (p<0.01) and haemoglobin (p<0.001), as well as significant reductions of platelets antigenemia p24 (p<0.001) and viral load (p<0.01). Moreover, only cardiovascular, obese and hypertensive disease-induced HAART therapy patients under IM28 showed restoration of body levels in lipids, glucose and normalization of blood pressure. These data unequivocally suggest therapeutic proprieties to IM28 for HIV-1 and cardiovascular-induced HAART therapy. These open new promising insights for IM28.