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Incidence of HIV Superinfection Following Primary Infection
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Reported by Jules Levin
11th Annual Retrovirus Conference
San Francisco, Feb 8-11, 2004
There are several studies at the conference examining superinfection, which is when a person who has HIV gets infected with a second viral strain of HIV through sex or injection drug use. There is some controversy about whether superinfection can occur. At the 2003 Resistance Workshop there was much discussion about superinfection by sex and IDU. Most researchers agreed it is real and understudied and underreported problem. Here is link to NATAP report from Workshop:
http://www.natap.org/2003/resistance/day2.htm
Abstract 21. Authors: D Smith*1, J Wong1, G Hightower1, K Kolesch1, C Ignacio1, E Daar2, D Richman1,3, and S Little1 1Univ. of California, San Diego, USA; 2Univ. of California, Los Angeles, USA; and 3San Diego VA Healthcare Systems, La Jolla, CA, USA
Anecdotal reports of HIV superinfection coupled with systematic investigations of chronically infected individuals who could not identify cases of superinfection prompted our investigation in a cohort of newly infected individuals.
We retrospectively analyzed plasma samples from 54 subjects enrolled in the San Diego and Los Angeles Acute HIV Infection and Early Disease Research Programs who deferred ARV treatment for 6 months or longer (46 subject-years of follow-up). Population-based sequencing of the pol gene was performed (Viroseq, Celera Diagnostics) from RNA extracted from plasma at 2 times (mean 313, range 177 to 597 days apart). Superinfection was suspected when phylogenetic analysis showed that the 2 sequences clustered independently. Superinfection was confirmed by clonal (V3) and dye-primer (pol) sequencing and length polymorphism analysis (V1-2 and V4-5) (GeneScan, Applied Biosystems).
We identified 3 cases of superinfection, representing a rate of 6.5% per year. Superinfection occurred 5 to 13 months after the estimated date of initial infection. All 3 subjects were male whose risk factor was sexual exposure; each superinfecting HIV strain was associated with a change in ARV susceptibility. Two were initially infected with drug-resistant HIV and then became superinfected with a wild-type strain, while the other was initially infected with a wild-type strain and then was superinfected with a drug-resistant strain. Within 6 months of acquiring the superinfecting strain, plasma viral loads increased (mean 1.6 log) and CD4 counts decreased (mean 132 cells/µL).
While initial co-infection cannot be ruled out, 4 independent lines of molecular investigation provide compelling evidence that these are cases of HIV-1 clade-B superinfection. Since population-based pol sequencing is a conservative screening method, this may underestimate the true superinfection rate. Other cases may have been missed if the superinfecting strain was a minor variant below the level of detection, or if the superinfecting strain replaced its original pol gene with the initial HIV strain’s pol gene through recombination. Harm reduction counseling with patients is essential even if their risk exposures are with other HIV-infected people, as superinfection could have detrimental clinical consequences by accelerating disease progression and limiting future treatment options.
NATAP recent report on Superinfection:
http://www.natap.org/2004/HIV/020504_03.htm
HIV-1 Superinfection in a Rapid Disease Progressor: Rapid Replacement of the Initial Strain with the Superinfecting Virus by Natural Selection
G Gottlieb*1, D Nickle1, M Jensen1, K Wong1, R Kaslow2, J Margolick3, and J Mullins1 1Univ. of Washington, Seattle, USA; 2Univ. of Alabama at Birmingham, USA; and 3Johns Hopkins Univ., Baltimore, MD, USA
Superinfection with a second strain of HIV-1 has important implications for understanding HIV transmission and for vaccine development. However, the frequency and pathogenic consequences of superinfection are largely unknown, as are the underlying host-virus interactions associated with HIV-1 superinfection.
From the Multicenter AIDS Cohort Study (MACS), 32 seroconverters were retrospectively evaluated for HIV-1 superinfection using a combination of heteroduplex mobility assay (HMA), sequencing of the envelope C2-V5 region, and phylogenetic methods. HLA class II typing of samples was used to confirm superinfection. Subjects were also typed for HLA and CCR variants known to influence disease progression. Outcome of HIV infection was measured using: time to clinically defined AIDS, time to CD4+ T-cell count <200/mL, and plasma RNA viral load. Phylogenetic and population genetic methods were used to analyze viral dynamics.
HIV-1 superinfection was detected in 1 of 32 subjects. Superinfection in this subject occurred with a second HIV-1 subtype B strain between 0.8 and 1.3 years post-seroconversion (SC). In this subject time from seroconversion to a CD4+ T-cell count <200/ul was 2.4 years and time from seroconversion to AIDS (PCP) was 3.4 years. There was rapid replacement of the initial virus by the superinfecting virus in plasma within 6 months, and no evidence of the initial strain in PBMC at 3.3 years post-SC. By population dynamic and phylogenetic analyses, random genetic drift could not completely explain replacement by the superinfecting virus. In addition, this subject’s HIV viral load, and pattern of HLA and CCR polymorphisms did not fully explain his rapid disease progression.
This is the first description of a case of HIV-1 superinfection in an individual with rapid progression to AIDS. Emergence of, and replacement by, the superinfecting virus appears to have occurred under selective pressure. It is not clear, however, whether superinfection leads directly to rapid progression, or whether certain hosts, who are intrinsically more likely to experience a rapid disease course, are also less likely to restrict new infections.
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