Characterization of HIV-1 diversity in various compartments at the time of primary infection by ultradeep sequencing

We used next-generation sequencing to evaluate the quantity and genetic diversity of the HIV envelope gene in various compartments in eight patients with acute infection. Plasma (PL) and seminal fluid (SF) were available for all patients, whole blood (WB) for seven, non-spermatozoid cells (NSC) for four, and saliva (SAL) for three. Median HIV-1 RNA was 6.2 log₁₀ copies/mL [IQR: 5.5-6.95] in PL, 4.9 log₁₀ copies/mL [IQR: 4.25-5.29] in SF, and 4.9 log₁₀ copies/mL [IQR: 4.46-5.09] in SAL. Median HIV-1 DNA was 4.1 log₁₀ copies/10⁶ PBMCs [IQR: 3.15-4.15] in WB and 2.6 log₁₀ copies /10⁶ Cells [IQR: 2.23-2.75] in NSC. The median overall diversity per patient varied from 0.0005 to 0.0232, suggesting very low diversity, confirmed by the clonal aspect of most of the phylogenetic trees. One single haplotype was present in all compartments for five patients in the earliest stage of infection. Evidence of higher diversity was established for two patients in PL and WB, suggesting compartmentalization. Our study shows low diversity of the env gene in the first stages of infection followed by the rapid establishment of cellular reservoirs of the virus. Such clonality could be exploited in the search for early patient-specific therapeutic solutions.