More than 15 years after the introduction of
highly active antiretroviral therapy, HIV/
HAART-associated
lipodystrophy syndrome still shadows the indisputable efficacy of antiretroviral
therapy. Several issues related to this complication (prevalence, diagnosis, pathogenesis, prevention, or clinical management) have not been completely clarified. However, in the last years, substantial progress has been made in elucidating some of these basic aspects. This includes a better knowledge of the pathogenic mechanisms underlying HIV/
HAART-associated
lipodystrophy syndrome such as genetic host determinants, the impact of
HIV infection per se, as well as the contribution of antiretroviral
therapy. In regard to treatment, we have learned that certain drugs are especially prone to cause HIV/
HAART-associated
lipodystrophy syndrome (i.e.
thymidine analogues). Pharmacological interventions to treat this condition have yielded mostly disappointing results, and the only intervention which offers an immediate aesthetical improvement for patients with HIV/
HAART-associated
lipodystrophy syndrome is plastic surgery. Even under the most favorable conditions (ideal host genetic make-up, and the timely initiation of HIV
therapy with less toxic drugs), current data show that HIV/
HAART-associated
lipodystrophy syndrome is a complication of
HIV infection and/or antiretroviral treatment that we are unable to avoid. In the context of HIV-1-infected patients under long-term antiretroviral
therapy, fat toxicity is still the dark side of the rainbow.