Transmitted drug resistance associated with transmission clusters in newly diagnosed antiretroviral-naïve patients in Northern Greece

Purpose of the study

To determine the contribution of transmission clusters on transmitted drug resistance (TDR) in newly diagnosed antiretroviral naive patients in Northern Greece, during 2000 -2007.

Methods

Viral reverse transcriptase and protease genes from 369 individuals with newly diagnosed HIV-1 infection were sequenced at baseline. A maximum-likelihood phylogenetic analysis method was employed to examine for linkage between viral isolates. Clinical data were retrieved from the database and cross-referenced with the patients' medical files. Transmitted drug resistance was defined in accordance with the Surveillance Drug Resistance Mutation (SDRM) 2009 list.

Results

The study population characteristics were as follows: 82.8% male, 89.7% of Greek nationality, mean age 38, median CD4 cell count at diagnosis 295 cells/µl and mean HIV-1 RNA 4.94 log10 copies/ml. The most prevalent risk exposure category was men who have sex with men 59.1% (n=218) followed by heterosexual transmission 21.4% (n=79) and intravenous drug use 7.6% (n=28). Subtype B viruses were most prevalent (53.1%), followed by subtype A (32.5%). At least one drug resistance mutation was identified in 46/369 patients (12.4%). Twenty-eight patients (7.6%) harbored resistance mutations to nucleoside/nucleotide RT inhibitors, 20 patients (5.4%) to non-nucleoside RT inhibitors and 12 patients (3.3%) to protease inhibitors (PIs). Dual-class resistance mutations were identified in 14 patients (3.8%). The median CD4 cell count in patients with TDR was not significantly different compared to patients without (p=0.072). Phylogenetic analyses, supported by bootstrapping >90% and genetic distance <0.015, revealed three transmission clusters involving drug resistant strains, including one cluster of 11 patients infected with a strain carrying RT mutations Y181C and T215 variants conferring NRTI and NNRTI resistance.

Conclusions

The overall prevalence of TDR in our study population was 12.4%. Phylogenetic analyses of viral sequences from these new diagnoses demonstrated the impact of transmission clusters on the primary drug resistance. The outbreak of dual-class TDR, coupled with late HIV diagnosis in this population may require improved public health interventions.