Session 25Oral Abstract Presentations Viral Pathogenesis Session Day and Time: Thursday 10 am - 12:30 pm Presentation Time: 11:30 Room: Ballroom A
126 Dual HIV-1 Infection Associated with Rapid Disease Progression Geoffrey S. Gottlieb*1, David C. Nickle1, Mark A. Jensen1, Kim G. Wong1, Fusheng Li1, Shan-Lu Liu1, Cecilia Rademeyer2, Gerald H. Learn1, Salim S. Abdool Karim3, Carolyn Williamson2, Lawrence Corey1, Joseph B. Margolick4, James I. Mullins1 1Univ of Washington,Seattle; 2Univ of Cape Town, South Africa; 3Univ of Natal, Durban, South Africa; and 4Johns Hopkins Bloomberg Sch of Publ Hlth, Baltimore, MD
Background: Infection with more than one strain of HIV has important implications for understanding HIV transmission and for vaccine development, and has led to numerous instances of recombinant viral strains of global epidemiologic significance. However, the frequency and pathogenic consequences of "dual infection" (with 2 or more distinct HIV-1 variants) are largely unknown. We previously reported the case of a homosexual male (patient B) who was dually infected with 2 distinct HIV-1 subtype B virus strains, and who progressed to AIDS within 1.5 yrs of seroconversion. Given the unusually rapid disease course in this dually-infected individual, we hypothesized that dual HIV-1 infection may be associated with rapid progression to AIDS.
Methods: We have screened a total 47 subjects from the MACS, Seattle Primary Infection Cohort, and South African FSW Cohort for dual infection using a combination of Heteroduplex Mobility Assay (HMA) and sequencing of the envelope C2-V5 region. Phylogenetic methods were used to confirm dual infection.
Results: We found 4 patients (pts) to be dually infected with HIV-1. All 4 cases were examples of intra-subtype dual infection (3 pts with subtypes B, B and 1 pt with subtypes C, C). All 4 dually-infected pts appeared to be cases of co-infection, as opposed to superinfection as both viruses were present at or near the first seropositive time point. In all 4 cases, times from seroconversion to a clinical AIDS defining event or death were less than 2 yrs, and times from seroconversion to CD4+ T-cell count < 200/ml were less than 3.1 yrs. Early "set point" HIV plasma RNA viral loads, as measured by the average of available post-seroconversion first year values, ranged from 4.6 to 5.8 log10 copies/mL for the 4 dually-infected pts.
Conclusions: This is the first study to suggest an association between dual infection and rapid disease progression. These 4 dually-infected pts had some of the fastest disease progression rates described to date. It is not clear, however, whether dual infection leads to rapid progression or whether some hosts less capable of suppressing HIV infection, and thus likely to develop a rapid disease course, were also less likely to restrict new infections. Our initial finding of an association between dual infection and rapid disease progression should prompt larger studies to access its impact on at the population level.
