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Dolutegravir Monotherapy in HIV-Infected Naive Patients With <100,000 Copies/mL HIV RNA Load
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JAIDS Journal of Acquired Immune Deficiency Syndromes: May 1 2016 Lanzafame, Massimiliano MD; Gibellini, Davide PROF; Lattuada, Emanuela MD; Signoretto, Caterina MD; Mazzi, Romualdo MD; Concia, Ercole PROF; Vento, Sandro PROF Units of *Diagnosis and Therapy of HIV Infection
Infectious Diseases, G.B. Rossi University Hospital, Verona, Italy
┬žDepartment of Medicine, School of Medicine, Nazarbayev University, Astana, Kazakhstan
To the Editors:
Dolutegravir is an HIV integrase inhibitor with a potent antiviral activity, distinct resistance profile, and favorable pharmacokinetic profile1 recently approved for use in naive and highly active antiretroviral therapy-experienced patients. Its efficacy and safety have been demonstrated in various clinical trials conducted both in naive and experienced patients.2 In dose-ranging study, dolutegravir monotherapy has shown a potent antiviral activity, with a significant reduction in plasma HIV RNA levels from baseline to day 11 for various doses.1 Dolutegravir is approved for use in association with an abacavir/lamivudine or emtricitabine/tenofovir backbone in antiretroviral naive patients at a 50-mg once-daily dose. In 3 phase III randomized controlled clinical studies in antiretroviral naive patients, dolutegravir plus 2 nucleoside reverse transcriptase inhibitors was superior to both tenofovir/emtricitabine/efavirenz and darunavir/ritonavir regimens, and noninferior to raltegravir.3-5 We report our experience in 9 antiretroviral naive HIV-1-infected patients followed at the Infectious Diseases Outpatient Department of G.B. Rossi Hospital in Verona, Italy, who started dolutegravir monotherapy after refusing nucleoside reverse transcriptase inhibitors. They all gave written informed consent to the use of dolutegravir as only antiretroviral drug. Seven men and 2 women were all HIV monoinfected, with a mean age of 45 years (range, 36-76). Pretreatment characteristics of the patients, HIV RNA level (at baseline), number of CD4 cells (at baseline), HIV RNA level 4 weeks after starting treatment and at last visit, number of CD4 lymphocytes at the last control, residual plasma HIV RNA 3 and 6 months after the beginning of dolutegravir, and duration of dolutegravir monotherapy are indicated in Table 1. No patients had baseline HIV resistance mutations for NRTI, NNRTI, PI, or INSTI. The second table shows total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterols, and triglycerides levels before starting dolutegravir and at the last control. For CD4 cell count, the mean increase was 191 cells per microliter. Serum lipids increased importantly only in 1 patient (no. 1, Table 2), who had also an increase in her body weight. The treatment of HIV infection continues to be based on the combination of 3 antiretroviral drugs. Monotherapy with protease inhibitors in antiretroviral naive patients is inferior to standard antiretroviral regimens in clinical studies.6 Dolutegravir in association with 2 nucleosides is superior to efavirenz and darunavir in naive patients.3,5 Dolutegravir 50 mg daily showed a high antiviral potency with a reduction of viral load of 2.5 log10 after 10 days of monotherapy. Recently, a combination of dolutegravir and lamivudine was virologically effective in 20 treatment-naive patients in a pilot study.7 The results of our small and time-limited study suggest the feasibility of a dolutegravir monotherapy in patients with a viral load lower than 100,000 copies per milliter. Should well powered clinical trials with long follow-up confirm our results, a dolutegravir monotherapy strategy could be used to preserve future antiretroviral drug options, reducing side effects and health care costs.


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