HIV-1 genotypic drug resistance in patients with virological failure to single-tablet antiretroviral regimens in southern Taiwan

Abstract

Purpose: Sparse data are available on the prevalence of resistance among HIV-1-infected patients with virological failure to a single-tablet regimen (STR). This study aimed to evaluate the prevalence of HIV genotypic drug resistance in HIV-1-infected patients with virological failure to STRs in southern Taiwan.

Patients and methods: This retrospective study investigated drug resistance in patients with virological failure to STR from January 2016 to September 2017. Antiretroviral resistance mutations were defined using the 2017 International AIDS Society-USA HIV drug resistance algorithm, and drug resistance was compared using the HIVdb program of the Stanford University HIV Drug Resistance Database. Variables between resistance and non-resistance groups were compared.

Results: Thirty-nine HIV-1-infected patients with treatment failure were tested for resistance, of whom 89% were infected by men who have sex with men. Subtype B HIV-1 strains were found in 90% of the patients. Eight patients were treatment naïve and initiated STRs, while 31 patients experienced treatment failure after switching to STRs. Eighty-seven percent of the patients harbored any of four classes of resistance (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors (PIs), and integrase strand transfer inhibitors). The prevalence rates of nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, PI, and integrase strand transfer inhibitor resistance were 72%, 82%, 10%, and 3%, respectively. Patients with PI resistance were more likely to respond to treatment with a non-tenofovir disoproxil fumarate/emtricitabine/efavirenz-based STR (.=0.004) and a longer duration of antiretroviral therapy (101 months [72.0-123.3] vs 11 months [7-44], P=0.007). There were no associations between different STRs and transmission risk factors, HIV subtype, duration of antiretroviral therapy, and resistance to tenofovir disoproxil fumarate.

Conclusion: A high rate of antiretroviral drug resistance was found in the patients who failed STR treatment. The presence of PI resistance in these patients represented an inappropriate switch from a multiple tablet regimen to an STR. These findings should remind clinicians that detailed drug resistance history and close monitoring are mandatory after switching to an STR.

Keywords: HIV; antiretroviral therapy; drug resistance; single-tablet regimen; treatment failure.

Figure 1

Drug resistance according to the HIVdb program of Stanford University among 39 HIV-1-infected patients with virological failure to STRs. Note: The figure shows 87% drug resistance to any of the four classes of antiretroviral drugs, including 72% resistance to NRTI, 82% resistance to NNRTI, 10% resistance to PI, and 3% resistance to INSTI. Abbreviations: INSTI, integrase strand transfer inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; STR, single-tablet regimen.

Figure 2

The prevalence of drug resistance to NRTI, NNRTI, PI, and INSTI among 39 HIV-1-infected patients with virological failure to STRs. Notes: The figure shows that 5% of the 39 STR users were resistant to zidovudine, 23% to tenofovir disoproxil fumarate, and 10% were resistant to atazanavir/ritonavir or lopinavir/ritonavir. Of the patients who failed Complera or Triumeq treatment, 38% and 33% were resistant to atazanavir/ritonavir or lopinavir/ritonavir, respectively. Abbreviations: INSTI, integrase strand transfer inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; STR, single-tablet regimen.

Figure 3

Percentage of HIV drug resistance-associated mutations to NRTI, NNRTI, PI, and INSTI among the 39 HIV-1-infected patients with virological failure to STRs. Abbreviations: INSTI, integrase strand transfer inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; STR, single-tablet regimen.

Figure 4

The prevalence of drug resistance-associated mutations to NRTI, NNRTI, PI, and INSTI among the 39 HIV-1-infected patients with virological failure to STRs. Notes: The figure shows that the most common NRTI drug resistance-associated mutations were M184V/I (71.8%) and K65R (17.9%). For NNRTI, the mutations were K103N (35.9%), V179D (33.3%), Y181C (12.8%), and L100I (12.8%), and those for PI were K20T (7.7%) and L90M (5.1%). One of the three patients (33.3%) who failed Triumeq treatment had E138K, G140S, and Q148H INSTI mutations. Abbreviations: INSTI, integrase strand transfer inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; STR, single-tablet regimen.