Background: To evaluate whether drug susceptibility and viral replication capacity (RC, e.g., fitness) are associated with baseline plasma viral load levels in treatment naïve subjects with primary HIV infection.

Methods: Baseline plasma viral load (VL), drug susceptibility, RC, and pol sequence analysis were evaluated a median of 119 days after the estimated date of HIV infection for 202 treatment naïve subjects. Drug resistance results have been previously reported in part for these subjects. Drug susceptibility and RC were measured using PhenoSense™ HIV. ABI sequence analysis of pol was used to identify drug resistant mutations. Longitudinal phenotype and RC data were available (median 28 months) for a subset of 9 untreated subjects.

Results: Subjects were predominantly men (91%) of white, non-Hispanic race (73%), whose risk for HIV infection was sex with men (73%). Median VL at baseline was not significantly different among subjects infected with drug resistant virus, defined by phenotype as a > 10 fold reduction in susceptibility to at least one drug (4.71 log₁₀ copies/ml) and by genotype as the detection of at least one major drug resistance mutation or 215 D/N/S/C/E (median 4.75 log), compared to subjects infected with drug sensitive virus as defined by phenotype (median 4.94 log) or genotype (median 4.88 log). Hypersusceptibility (HS), defined as an IC₅₀ fold-change ≤ 0.4, to one or more protease inhibitors (PI) was noted in 27% of subjects. The median RC in subjects with either PI HS virus (29%) or phenotypically resistant virus (32%) at baseline was significantly lower than for subjects with drug susceptible virus that did not exhibit PI HS (48%, p < 0.01). Baseline VL was significantly higher (5.06 vs 4.69 log, p = 0.005) for subjects with baseline RC values above the median RC of 42% for the entire group. No significant change in RC or plasma VL was noted among 9 subjects with longitudinal follow-up (s.e. log RC = 0.12, s.e. log VL = 0.46).

Conclusions: Higher baseline viral RC, but not drug resistance, was a significant predictor of higher baseline viral load in subjects presenting with primary HIV infection. PI HS and phenotypic resistance were associated with a lower baseline RC. Although the clinical significance of RC requires further study, it may be an important determinant of the rate of disease progression among untreated patients with recent HIV infection.