Infect Chemother.  2018 Sep;50(3):252-262. 10.3947/ic.2018.50.3.252.

Effectiveness, Safety, and Tolerability of a Switch to Dual Therapy with Dolutegravir Plus Cobicistat-Boosted Darunavir in Treatment-Experienced Patients with Human Immunodeficiency Virus

Affiliations
  • 1Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea. ksw2kms@knu.ac.kr

Abstract

BACKGROUND
Dual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG/DRV/c) is reasonable alternative option for patients with existing resistance and/or intolerance to nucleoside reverse transcriptase inhibitors (NRTIs). MATERIAL AND METHODS: All patients who switched to DTG/DRV/c among treatment-experienced patients with human immunodeficiency virus (HIV) in a tertiary university hospital were selected. We analyzed the effectiveness, safety, and tolerability based on serial laboratory data and clinical findings. The primary endpoint was defined as the proportion of patients with plasma HIV RNA below 50 copies/mL at week 48 after switch. Secondary endpoints included evaluation of safety and tolerability.
RESULTS
Thirty-one patients were retrospectively analyzed. The main reasons for the change to DTG/DRV/c were treatment failure in 13 patients (41.9%), simplification in 12 patients (38.7%), and adverse drug reaction in 6 patients (19.4%). Among the 13 patients who switched owing to treatment failure, the proportion of patients in whom the viral loads were suppressed to less than 50 copies/mL increased from 0% at baseline to 45% at 4 weeks, 50% at 12 weeks, 50% at 24 weeks, and 66.7% at 48 weeks. HIV virus levels decreased and CD4⁺ T cell counts increased during the follow-up period. In non-treatment failure patients (18 patients), the levels of viral suppression and CD4⁺ T cells were maintained. There were no significant differences in renal function, liver function, glucose levels, and lipid profile before and after regimen changes. The tolerability was very good: 30 patients (96.8%) tolerated the drugs well and only 1 patient discontinued owing to no improvement in renal insufficiency. Two patients (6.4%) in treatment failure group failed to reach viral suppression.
CONCLUSION
The use of DTG/DRV/c in HIV treatment-experienced patients appears to be a very good regimen for switch therapy that is effective and well tolerated, without significant adverse drug reaction.

Keyword

Dolutegravir; Darunavir; Cobicistat; Human immunodeficiency virus

MeSH Terms

Cell Count
Cobicistat
Darunavir*
Drug-Related Side Effects and Adverse Reactions
Follow-Up Studies
Glucose
HIV*
Humans
Humans*
Liver
Plasma
Renal Insufficiency
Retrospective Studies
Reverse Transcriptase Inhibitors
RNA
T-Lymphocytes
Treatment Failure
Viral Load
Cobicistat
Darunavir
Glucose
RNA
Reverse Transcriptase Inhibitors

Figure

  • Figure 1 Percentage of patients with HIV-1 RNA counts less than 50 copies/mL in the failure group.HIV, human immunodeficiency virus; RNA, ribonucleic acid; n, number of the patients.

  • Figure 2 Mean changes in HIV RNA titer (A) and CD4+ T cell count (B). In the failure group (purple line), suppression of the HIV RNA titer decrease is shown and CD4+ T cell count increased. In the non-failure group (orange line), virus suppression and high CD4+ T cell levels are maintained.HIV, human immunodeficiency virus; RNA, ribonucleic acid.

  • Figure 3 Drug tolerability can be used to determine drug adherence (by Kaplan-Meier plot with 0.2 P-value threshold entering multiple regression). Tolerability is determined by whether each group continued taking this regimen without dropout during the follow-up period.


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