Genetic diversity from proviral DNA as a proxy for time since HIV-1 infection. Journal of Infectious Diseases
HIV-1 RNA genetic diversity predicts time since infection, which is important for clinical care and research. It is unclear, however, whether proviral DNA genetic diversity sampled under suppressive antiretroviral therapy can be used for this purpose.
In this study, the authors tested whether proviral genetic diversity from next-generation sequencing predicts time since infection and recency in 221 people with HIV-1 with known infection time.
Proviral diversity was significantly associated with time since infection (P < 5×10−7, R 2 up to 25%) and predictive of treatment initiation during recent infection (area under the curve-receiver operating characteristic up to 0.85). Predictive accuracy was lower than that of viral diversity derived from plasma HIV-1 RNA, in particular when partial sequences were included. When restricting the analysis to full-length sequences and hypermutation filtering, predictive performances were in the range of what is achieved with treatment-naive plasma RNA for pol/env (AUC of 0.84/0.85 for proviral DNA compared to ≥0.95 for viral RNA).
In summary, this work shows the utility of average pairwise diversity scores derived from proviral sequences as a proxy for the time since infection and for prediction of infection recency. This may be useful for people with HIV without a baseline drug resistance test to decide on treatment simplification strategies in clinical practice or to determine infection recency in HIV research, for example, to retrospectively estimate HIV-1 incidence.