According to Dr. Jeffrey Klausner, "We have all sorts of levels of evidence ... and it's all pointing in the same direction: The crystal meth epidemic is playing an important role in increasing sexual risk behaviors, and that is leading to new HIV and STD infections."

According to New York's Pride Institute, "We're seeing a strong correlation between anal sex and HIV infection ... People who have weathered years of staying safe are getting into methamphetamine and then testing positive." A 2002 study at a San Francisco HIV clinic found that up to 30% of those with new HIV infections had used the drug in the previous six months. New York's Callen-Lorde Community Health Centre claims two-thirds of clients testing HIV-positive since June 2003 say methamphetamine was a component in their becoming positive.

In a 2001 study of HIV-positive men who use methamphetamine, 84% reported engaging in risky sexual behaviour; most tended not to disclose their HIV status to casual partners, and reported that, unless told otherwise, they assumed their sex partner(s) to be HIV-positive. Many participants reported a major increase in methamphetamine use after being diagnosed HIV-positive. Others reported using methamphetamine to deal with sources of emotional pain, such as social rejection and negative self-perceptions about being HIV-positive or memories of childhood abuse.

HIV-positive men who have unprotected sex with other HIV-positive men risk re-infection ("super-infection") or contracting more virulent and/or drug-resistant strains of the virus. According to some sources, some men who were assumed to be immune to HIV have seroconverted since starting to use methamphetamine. There are concerns that "aggressive" and difficult to treat forms of HIV may spread among methamphetamine users. Some HIV-positive individuals are using methamphetamine to deal with chronic fatigue, to alleviate the side effects of their prescription medication, alleviate depression, and escape negative self-perceptions.

Some drugs used in the treatment of HIV inhibit the body's ability to break down methamphetamine. Some users (especially heavy or longterm users) who are HIV-positive experience an increase in viral load (the amount of HIV in the body). Methamphetamine also contributes to the depletion of T-cell counts, prevents users from adhering to their drug regimens, contributes to the development of basal ganglia dysfunction (a type of dementia), and stimulates HIV replication in brain cells as much as fifteen-fold, according to an Ohio State University study. In addition, methamphetamine use is immuno-suppressive due to the missed meals, vitamin depletion, weight loss and disrupted sleep that accompany binges.