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In response to the HIV-AIDS pandemic, great strides have been made in developing molecular methods that accurately quantify nucleic acid products of HIV-1 at different stages of viral replication and to assess HIV-1 sequence diversity and its effect on susceptibility to small molecule inhibitors and neutralizing antibodies. Here, we review how knowledge gained from these approaches, including viral RNA quantification and sequence analyses, have been rapidly applied to study SARS-CoV-2 and the COVID-19 pandemic. Recent studies have shown