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Relationship between HIV co-receptor tropism and disease progression in persons with untreated chronic HIV infection
Presented by Matthew Goetz, United States.
Goetz M.1, Leduc R.2, Kostman J.3, Labriola A.4, Lie Y.5, Weidler J.5, Coakley E.5, Luskin-Hawk R.6, Long Term Monitoring (LTM) Study, Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA 060)
1VA Greater Los Angeles Healthcare System, Infectious Diseases/Medicine, Los Angeles, United States, 2University of Minnesota, Minneapolis, United States, 3UPHS/Presbyterian Medical Center, Philadelphia, United States, 4VA Washington Medical Center, Washington, United States, 5Monogram Biosciences, South San Francisco, United States, 6Saint Joseph Hospital, Chicago, United States
Objectives: To assess the effect of HIV co-receptor tropism on disease progression in prospectively followed, treatment-naïve HIV-infected patients.
Methods: At study entry, eligible patients were treatment-naïve and had ³450 CD4+ cells/mL and ³1,000 HIV RNA copies/mL. Tropism was retrospectively assessed using the Trofile assay (Monogram Biosciences).
Results: Results were available from 294 persons, 32 patients had dual/mixed R5/X4 (DM) tropic virus and 262 had R5 virus. Patients with R5 virus were less often Latino/a (8% vs 25%), otherwise no demographic differences were found. The median CD4+ count was higher in persons with R5 vs. DM virus (624 vs. 571) but the VL (4.1 vs 4.4 log10), age (38 years) and duration of known HIV infection (48 months) or study follow-up (52 months) did not differ.
Patients with DM virus progressed more rapidly (p=0.004) to the composite outcome of CD4+ count <350 (n=106), treatment initiation (n=59) or death (n=8). After adjusting for age, gender, race, IDU, MSM contact, HBV and/or HCV seropositivity, known duration of HIV infection and prior AIDS diagnoses, the relative risk of progression was 2.11 (p=0.004) for DM vs. R5 virus, 1.91 per 1.0 log10 higher VL (p<0.001) and 0.86 per 50 cell higher CD4+ count (p<0.001). The effect of DM tropism was also significant in separate regression analyses of time to CD4+ count <350 or time to treatment initiation.
Conclusion: Untreated patients with DM tropic virus vs. R5 tropic virus have a faster rate of HIV disease progression, whether assessed by a composite outcome of CD4+ count <350, treatment initiation or death, or by separate analyses of time to CD4+ count <350 or treatment initiation. Compared with R5 tropism, the effect of DM tropism was similar to a 1.0 log10 increase in VL. These data confirm and extend previous reports about DM tropism and disease progression.
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