Characteristics of Incidence Seroconverters and their Predominant Viral Type: Findings from a Population-Based Cohort

Objective: To characterize the individuals who acquired HIV in domestic HIVNET studies in 1995-97, their CCR5 status, viral phenotype, initial viral load and CD4 count, and prevalence of antiretroviral resistance among the first isolates.

Design: 4892 individuals were enrolled in the HIVNET Vaccine Preparedness study and followed semi-annually for 18 months. HIV seroconverters were offered enrollment in the HIVNET Infected Participant Cohort (IPC) with follow-up every 3 months for 18 months and then semi-annually. Viral load using Roche PCR (limit of detection >200 copies), viral phenotype, genotype, CCR5 status by PCR, and lymphocyte subsets were performed on specimens from the initial visit. Antiviral genotypic resistance was assessed by Affymatrix assays. Seroconverters were interviewed about the most likely source partner and asked to refer partners for viral load, phenotype and heteroduplex tracking (HTA) analysis.

Results: 99 seroconverters (86 M, 13 F) were enrolled in HIVNET IPC an average of 6 months after estimated seroconversion, of whom 82 were gay men, 10 IDUs, and 7 women at heterosexual risk. 58 of 93 (62%) seroconverters with > 1 follow-up visit used antiretrovirals. All had CLADE B virus. Initial median plasma viral load was 25, 662 (<200-608,599) and initial CD4 count was 587 (170-1,432). One seroconverter was homozygous for the 35 bp deletion (35 bpΔΔ) for CCR5, 7 were heterozygous and 85 had wild-type CCR5. Of 88 seroconverters tested for phenotype, 95% had nonsyncitial-inducing (NSI) virus and 4 (5%) had syncitial-inducing (SI) phenotype isolated. Average CD4 counts were lower during follow-up among the 4 individuals with SI phenotype than those with NSI (p<.001). Two of the 4 had SI

phenotype isolated at their first IPC visit, including the participant with 35 bpΔΔCCR5, whose CD4 remained between 200-300 for 18 months on quadruple therapy. Of the first 38 plasma specimens tested for genotypic resistance, the majority of whom were tested for resistance before initiating treatment, 5.3% had an AZT-resistance mutation (rt M4IL) and 23% had single protease inhibitor mutations (pro LI0I, M36I, A7IV, V77I, or V92A). Three of 8 partners had closely matched viral types to the recently infected partner by HTA, one of which is awaiting confirmation by sequence analysis.

Conclusions: The 4 individuals with SI phenotype early after seroconversion had lower CD4 counts during follow-up. One seroconverter with SI and 35 bpΔΔCCR5 had a particularly rapid decline in CD4. HTA of 8 partner pairs suggests that the presumed source partner is often not the transmitter. The LOI and V82A protease mutations have not previously been observed without drug selection pressures; drug-selected protease variants may have been transmitted in these two cases. The phenotypic and clinical consequences of these single protease mutations remain to be determined.

Connie Celum
Pacific Medical Center
901 Boren Avenue, Suite 1300
Seattle, WA 98104