LOW AND HIGH-FREQUENCY TRANSMITTED DRUG-RESISTANCE MUTATIONS AMONG RECENTLY-INFECTED HIV-1 PATIENTS IN ISRAEL, 2000-2014

Introduction: Transmitted drug-resistant mutations (TDRM) occurring at low or high frequency, may hamper successful anti-HIV-1 therapy and impact future control of the HIV-1 epidemic. Recently-infected, therapy-naïve individuals are best suited for surveillance of such TDRM.

Methods: Historical samples from 80 recently-infected patients diagnosed between 2000 and 2014 in Israel were subjected to ABI-based sequencing (ABS) and MiSeq next-generation sequencing (NGS). DeepChek-HIV software was used to analyze the results.

Results: Most patients were males (80%); Men who have sex with men (MSM) was the major risk group (58.8%). Overall TDRM was detected in 8.8% of patients by ABS and 31.3% by NGS, ranging from 2.7% or 24.3%, respectively, in 2000-2007 to 13.9% or 37.2%, respectively, in 2008-2014. All ABS-detected TDRM were identified by NGS. The prevalence of TDRM impacting protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI) and nonnucleoside reverse transcriptase inhibitors (NNRTI) was 0%, 3.8% and 5%, respectively, for ABS analyses and 11.3%, 26.2%, 7.5%, respectively, for NGS analyses. Patients with NGS detected TDRM had significantly lower viral load (4.9 versus 5.7 median log copies/ml, p<0.05) and higher number of low prevalence non-synonymous reverse transcriptase (RT) mutations compared to those without NGS-detected TDRM. None had integrase resistance mutations. Minor TDRM did not persist in later samples and did not hinder successful treatment.

Conclusions: NGS can substitute ABS for surveillance of TDRM. Although rates of HIV-1 protease and RT TDRM in Israel are high and continue to increase from 2000 to 2014, minor TDRM do not become major species or interfere with therapy. The need for ongoing surveillance of low frequency TDRM should be revisited in a larger study.