AEGiS-15IAC: Clinical consequences of HIV superinfection.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Clinical consequences of HIV superinfection.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. TuOrB1140)

Smith DM, Wong JK, Hightower G, Koelsch KK, Igancio C, Daar E, Richman DD, Little SJ
University of California San Diego, San Diego, United States

BACKGROUND: Formal documentation of HIV superinfection (SI) in humans has only recently been reported. To investigate clinical consequences of SI, we studied 3 cases identified in a cohort of newly infected individuals.

METHODS: We retrospectively analyzed plasma samples from subjects enrolled in the San Diego and Los Angeles sites of the Acute HIV Infection and Early Disease Research Program who deferred antiretroviral (ARV) treatment for ≥6 months. Population-based RNA sequencing of pol was performed (Viroseq, Celera Diagnostics) from two timepoints (mean 313 days apart). Superinfection was suspected when phylogenetic analysis indicated paired sequences clustering independently and was confirmed by clonal (V3) and dye-primer (pol) sequencing and length polymorphism analysis (V1-2, V4-5) (GeneScan, Applied Biosystems). Viral loads (Amplicor, Roche), CD4 counts, and genotypic resistance testing (Viroseq, Celera Diagnostics) were then measured on collected samples of confirmed cases.

RESULTS: Superinfection occurred 5-13 months after the estimated date of initial infection. All were male and had sexual exposures as their HIV risk factor. Each 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. All three had relatively low viral load setpoints (<7,000 Copies/ml) initially but then increased a mean of 1.6 log within six months of acquiring the superinfecting strain, which was coincident with a decrease in CD4 counts (mean decrease of 132 cells/mul).

CONCLUSIONS: Superinfection negatively impacted each clinical course by increasing viral loads and decreasing CD4 counts. Furthermore, HIV drug resistance acquired through SI or masked by SI will undermine the value of a patient's prior drug resistant tests and history of prior antiretroviral use.

Keywords: AEGIS, HIV, Acquired Immunodeficiency Syndrome, HIV Seropositivity, Superinfection, Viral Load, CD4 Lymphocyte Count, HIV Infections, Anti-HIV Agents, HIV-1 Reverse Transcriptase, HIV Protease, HIV Protease Inhibitors, Genes, pol, Los Angeles, Humans, Male, genetics

040711
TuOrB1140