It is not known how cannabis reacts with anti-HIV drugs. A small American study found that cannabis use did not impact on the effectiveness of the protease inhibitor indinavir, even though the drugs use the same mechanism to pass through the body. However, protease inhibitors may increase THC levels (the active ingredient in marijuana) so smaller doses may have greater effects (i.e. getting stoned quicker)

There is no clear evidence that smoking cannabis in itself affects immunity, but smoking certainly does. If the drug is smoked, long-term use is known to cause many smoking-related respiratory and cardiovascular diseases such as asthma, bronchitis, emphysema and heart disease. This may be of particular concern to people with HIV who have suffered lung damage from TB, or to those with increased lipids from anti-HIV medication, as this may increase the risk of heart attack.

Smoking depletes the body's store of antioxidant nutrients, which can lower resistance to infection. Low levels of the antioxidant nutrients appear as symptoms of HIV infection emerge. Heavy smokers with HIV are especially vulnerable to the development of Pneumocystis Pneumonia (PCP). There is also evidence that smoking cannabis can cause cancers of the mouth, throat and lungs.