HIV superinfection (also called HIV reinfection) is a condition in which a person with an established human immunodeficiency virus infection acquires a second strain of HIV, often of a different subtype. These can form a recombinant strain that co-exists with the strain from the initial infection, as well from reinfection with a new virus strain, and may cause more rapid disease progression or carry multiple resistances to certain HIV medications. HIV superinfection may be interclade, where the second infecting virus is phylogenetically distinct from the initial virus, or intraclade, where the two strains are belong to the same clade (subtype). For a list of clades, see subtypes of HIV. People with HIV risk superinfection by the same actions that would place a non-infected person at risk of acquiring HIV. These include sharing needles and forgoing condoms with HIV-positive sexual partners. Cases have been reported globally and studies have shown the incidence rate to be 0–7.7% per year. Research from Uganda published in 2012 indicates that HIV superinfection among HIV-infected individuals within a general population remains unknown. Further research indicates that there have been 16 documented cases of superinfection since 2002. If a person is infected with a second virus before seroconversion to the first virus has taken place, it is termed a dual infection. Infection with a second strain after seroconversion is known as superinfection.
Immunology A study conducted in Kenya in 2007 shows that superinfection tends to occur during the course of the initial infection, that is during acute infection, or 1–5 years after initial infection, but not during the latency period. Thus, superinfection occurs after an immune response to the initial infection has already been established. It is unknown what aspects of the natural immune response to HIV may protect someone from superinfection, but it has been shown that cytotoxic lymphocyte responses do not seem to be protective. Immune responses to initial infection with a particular strain of HIV do not provide protection against superinfection with a different strain. The effect of neutralizing antibodies (NAb) is also unknown, but it has been shown that individuals with HIV tend not to have a NAb response prior to superinfection. In addition, it has been demonstrated that superinfection can occur in individuals that demonstrate a robust anti-HIV antibody response. The anti-HIV antibody response broadens and strengthens in individuals post-superinfection. The finding that superinfection occurs within and between HIV subtypes suggests that an immune response to initial HIV infection provide limited protection against infection by a new viral strain. This means that HIV-vaccine strategies made to replicate the host's immune response to HIV infection may not prevent new infections. Studies indicate that superinfection causes a spike in HIV viral load and a decrease in CD4+ cell count similar to those reported during primary HIV infection. Early studies of HIV superinfection analysed these spikes to diagnose cases of superinfection. It is unclear whether superinfection causes a sustained increase in viral load. The effect of superinfection on the progression of HIV infection is unclear because of its ambiguous effects on surrogate markers for the disease, such as an increase in viral load or a decrease in CD4 cell count. The potential of superinfection to cause rapid disease progression depends on viral and host factors. Cases of superinfection are yet to be identified in sufficient numbers to conduct detailed studies on the effect of superinfection on the host immune response.
Causes HIV superinfection is distinct from HIV dual infection, where an individual is simultaneously infected with multiple distinct viral strains. HIV superinfection involves an individual with HIV being infected by a new, phylogenetically distinct HIV strain. Early reports of HIV superinfection were observed in cases of co-infection with HIV-1 and HIV-2. Studies have shown that a lack of neutralizing antibodies against HIV-1 infection predisposes patients to superinfection. Additionally, the tendency of HIV-1 virions to recombine when two subtypes infect a single cell increases its susceptibility to HIV superinfection. Further evidence of superinfection stems from the fact that nearly 10% of HIV-1 infections are associated with a transmittable recombinant strain. HIV-1 virions are divided into nine subtypes, all of which are characterized by different rates of disease progression, viral load and sensitivity to assays used in detection. When a single cell is infected by two HIV-1 subtypes, they recombine, forming a new, transmittable recombinant strain.
Mechanism
Loss of immune control Following initial acute HIV infection, CD8+ T-cells control viral replication and maintain it at a viral set point. Following superinfection, CD8+ T-cells lose control over replication and it deviates from the set point. The mechanism responsible for this is unknown. A weakened T-cell response against the initial virus enables the superinfecting strain to resist immune control, resulting in an increased replication rate and subsequent viremia. Increased viral load and a declining T-cell response enables the superinfecting strain to recombine rapidly, further decreasing immune control.
Recombination HIV virions each contain a double-stranded RNA genome. When superinfection occurs, cells contain two different HIV strains. These can exchange genetic material such that an RNA strand from each strain is contained in a single virion. As this progeny virion infects new cells, the RNA template transcribed by viral reverse transcriptase changes, resulting in a reverse transcript with genetic material from both parental viruses. Recombination results in a rapid increase in HIV viral diversity, causing quicker adaptations to host immune response and resistance to ART. Recombination tends to produce two distinct recombinant forms, the presence of which are used as evidence of dual infection. The high prevalence of interclade recombinants increases the likelihood of superinfection being more widespread than reported.
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