HIV DNA Decay in a Treatment-Naive Patient Starting Dolutegravir Plus Lamivudine with Resistance Mutations to Integrase Inhibitors: A Case Report

Editor: Recent data from clinical trials highlight the efficacy of a two-drug strategy with lamivudine (3TC) plus dolutegravir (DTG) as first-line regimen in treatment-naive HIV-infected people living with HIV (PLWH).1 PLWH with transmitted resistance mutations, however, were not included in the two GEMINI trials and thus no data are available on the efficacy of such regimens in PLWH with primary resistances. In a recently published report,2 we described our initial experience in a small cohort of treatment-naive PLWH starting 3TC plus DTG in clinical practice. We would like to further analyze the case of a 23-year-old subject with Y188C and D232N resistance mutations starting 3TC+DTG. The D232N mutation, in particular, is a nonpolymorphic mutation selected in patients previously exposed to raltegravir3 and has been related to potential resistance to first-generation integrase inhibitors (INIs) raltegravir and elvitegravir. The subject was diagnosed with HIV infection in March 2019, with a peak HIV RNA value of 114,866 copies/mL and a nadir CD4+ cell count of 328 cell/mm3. Genotypic test was also performed, showing the mentioned resistance mutations. He subsequently started the two-drug regimen with a rapid decline in HIV RNA, reaching 48 copies/mL after 3 weeks from treatment initiation. His HIV RNA load became undetectable after 8 weeks and as of today, after 24 weeks, it is still undetectable. We also observed a steady improvement in immunological parameters; after 24 weeks his CD4+ cell count was 1,091 cell/mm3. Given the presence of the transmitted resistances, we further investigated the subject's virological status by evaluating total HIV-1 DNA levels, a marker of low-grade inflammation and viral reservoir dynamics.4 In our patient, baseline HIV-1 DNA quantification was 3.00 log10 copies/106 leukocytes. Initial decay was sharp, as HIV DNA levels decreased to 2.69 log10 copies/106 leukocytes after 4 weeks of treatment and to 2.37 log10 copies/106 leukocytes after 8 weeks