HIV and HPV can both cause chronic infections and are acquired during sexual contact. HIV infection results in a progressive loss of CD4+ T cells that is associated with an increased prevalence of HPV infections, type-specific persistence and an increase in HPV-associated malignancies. On the one hand this illustrates the important role of HPV-specific CD4+ helper T-cell immunity, on the other it shows the Achilles heel of the HPV-specific immune response. The use of highly active antiretroviral therapy (HAART) results in a rapid reduction of HIV and a reconstitution of systemic CD4+ T-cell levels. The use of HAART thus has the potential to raise immunity to HPV but to the surprise of many, the incidence of HPV-induced diseases has increased rather than declined since the introduction of HAART. Here, the knowledge on how HPV-induced diseases develop in the face of a non-compromised immune system will be used to explain why the effect of HAART on HPV-induced diseases is modest at best. Furthermore, exciting new data in the field of therapeutic vaccines against HPV will be discussed as this may form a more durable and clinically successful therapeutic approach for the treatment of HPV-induced high-grade lesions in HIV-positive subjects on HAART.