Infection with two different HIV isolates is possible. HIV superinfection occurs when a person with HIV infection acquires a second viral strain. In contrast, HIV co-infection refers to the situation where two viral strains are present at the time of initial infection.[43] Dual HIV infection collectively refers to both HIV superinfection and co-infection.[44] Dual infection is a prerequisite for recombination events, which occur between isolates from different HIV subtypes resulting in circulating recombinant forms of HIV (see Basic Virology and immunology - The taxonomy of HIV and the primate immunodeficiency viruses).
Cases of superinfection have been reported in a variety of situations including intersubtype;[45]intrasubtype;[46] wild-type with drug resistant;[47] drug-resistant with wild-type;[48] and R5 only with dual tropic.[49] Recombination of superinfecting viruses has been documented in people with chronic infection. This has involved intersubtype recombination[50] and intrasubtype recombination involving multiclass drug resistant viruses.[51]The exact incidence of superinfection is at present unknown. Cohort based studies have reported that superinfection occurs in 0-5% of patients with HIV.[52], [53], [54], [55], [56]
The consequences of superinfection are unknown for the individual and also HIV vaccine development. The implication is that the natural immune response to HIV infection is frequently not sufficient to provide protection from infection with another HIV variant, raising concerns for vaccine design.[57] Case reports have associated superinfection with accelerated clinical and surrogate marker progression.[58], [59] Superinfection with a drug resistant strain has been associated with impaired virological responses to ART.[60] However, not all cases of superinfection have been associated with poorer outcomes as this process has been documented in two patients with long-term non-progressive HIV disease.[61] Studies have been unable to distinguish between co-infection and superinfection; however, they have consistently associated dual infection with higher viral load set points.[62],[63] 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 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.[64],[65], [66], [67] To date, no case of superinfection has occurred in people taking ART.[68], [69] However, methods used in these studies may underestimate the true prevalence of superinfection. Case reports of superinfection with multiclass resistant HIV potentially suggest that even patients on ART may be at risk of superinfection.[70]