Almost 25 years have passed since the discovery of HIV and AIDS, and >25 antiviral drugs from various therapeutic classes are available at present. Despite these developments and the numerous educational campaigns that have been initiated worldwide, the numbers of HIV-infected patients in developing and industrialized countries are still increasing. Although the classical AIDS-related conditions have now become less common owing to highly active antiretroviral therapy (HAART), there is a significant risk of “non-AIDS”, early aging complications, including insulin-resistant diabetes mellitus, cardiovascular diseases, liver and kidney failures, and cancer in HIV-infected patients [1]. Even sustained and efficient medication combined with good compliance does not fully restore health, mandating the development of new strategies to avoid (re)infections. Therefore, gene-based therapies have been proposed as a long-term alternative to HAART (Table 1). In this context, one of the most promising approaches is to focus on the main coreceptor for HIV: the chemokine receptor CCR5.