P25.11
Background: Previous reports showed that HIV-1 viruses from early infection had shorter HIV-1 Env variable loops and could be more sensitive to neutralization. However, findings on HIV-1 subtype C and A were not confirmed with subtype B and there were uncertainties as to whether loop lengths evolved in the first weeks of infection. Here we characterized Env variable loops (V1-V5) in subjects newly infected (diagnosis at a median of 4 days after the last negative visit) with different HIV-1 subtypes.
Methods: We sequenced 1,204 HIV-1 strains from 49 subjects enrolled in Kenya, Tanzania, Uganda and Thailand at a median of 4, 33 and 171 days after diagnosis. These sequences were compared to 624 independent sequences from chronic infection.
Results: Reflecting the distribution of subtypes in Thailand and East Africa, our cohort included individuals infected with CRF01_AE (n=15), subtype A1 (n=10), C (n=4), and different A1/C/D recombinant strains (n=17). V1 loops varied between 8 and 34 amino acid (AA) (IQR=16-23), while V2 loops varied between 36 and 51 AA (IQR=40-44). Variable loop lengths did not differ between HIV-1 subtypes (p>0.230). Next, we compared loop lengths from our cohort to values from chronically infected subjects: for 280 sequences isolated past 2000, V1 loops varied between 5 and 42 AA (IQR=18-24), and V2 loops between 36 and 74 AA (IQR=40-45). There was no evidence that variable loops from acutely-infected individuals were shorter than those from chronically-infected individuals (p>0.188). Finally, we found that Env variable loop lengths did not increase over the first six months of follow-up in our cohort (p>0.352).
Conclusions: Env sequences sampled in the first week of HIV-1 infection showed a wide range of variable loop lengths, making them undistinguishable from sequences from chronic infection. Our findings indicate that viruses with shorter Env variable loops are not selected for in the establishment of HIV-1 infection.
