HIV superinfection occurs when a person with HIV infection becomes infected with another strain of HIV. ^[33,34] In contrast, HIV co-infection refers to the situation where two HIV strains are present at the time of initial infection. Dual HIV infection collectively refers to either HIV superinfection or co-infection. Dual infection is a prerequisite for genetic recombination events to occur between different HIV subtypes resulting in circulating recombinant forms (CRFs) of HIV (see section on Basic HIV Virology).

Cases of HIV superinfection have been reported in a variety of situations, including intersubtype; intrasubtype; wild-type with drug resistant; drug-resistant with wild-type; and R5-tropic only with dual tropic. Recombination of superinfecting viruses has been documented in people with chronic HIV infection. This has involved intersubtype recombination^[35] and intrasubtype recombination involving multiclass drug resistant viruses.^[36]  Cohort based studies have reported that superinfection occurs in 0-5% of patients with HIV infection.^{[37] [38] [39] [40]}  

The implications of HIV superinfection for HIV vaccine development, as well as the consequences for the infected individual, are currently unclear. The implications for vaccine development are that if the natural immune response generated by HIV infection is not sufficient to protect against infection with another strain of HIV, it might be difficult to do this with a vaccine.^[41] With regards to the HIV-infected individual, case reports have associated superinfection with accelerated clinical and surrogate marker progression.^[42]  Superinfection with a drug-resistant strain of HIV-1 has been associated with  impaired virological responses to ART.^[43] However, not all cases of HIV superinfection have been associated with poorer outcomes as this process has been documented in two patients with long-term non-progressive HIV disease.^[44] While studies have sometimes been unable to distinguish between HIV co-infection and superinfection, they have consistently associated dual infection with higher HIV viral load set points.^[45] On balance, evidence suggests that superinfection may have deleterious effects on HIV disease progression. It is not clear if superinfection itself leads to accelerated disease progression, or if unidentified host factors contribute to the accelerated disease progression independent of superinfection.

It is unknown if all HIV patients are at risk of HIV superinfection or when this is most likely to occur. However, superinfection has been documented to occur up to 12 years after initial infection. ^[46] To date, superinfection has not been reported in people receiving ART. ^[37] However, methods  used  in  these  studies  may  underestimate  the  true prevalence of superinfection. Case reports of superinfection with multiclass antiretroviral drug-resistant HIV potentially suggest that even patients on ART may be at risk of superinfection.^[36]