The Prevalence of Transmitted Drug Resistance in Newly Diagnosed HIV-Infected Individuals in Croatia: The Role of Transmission Clusters of Men Who Have Sex with Men Carrying the T215S Surveillance Drug Resistance Mutation

Abstract

The aim of this study was to determine the prevalence of transmitted drug resistance (TDR) in newly diagnosed and treatment-naive HIV-infected patients from Croatia and evaluate a possible contribution of transmission clusters to the spread of resistant virus. The study enrolled treatment-naive HIV-infected patients that entered clinical care at the Croatian Reference Center for HIV/AIDS between 2006 and 2008. The protease gene and a part of the reverse transcriptase gene of the HIV-1 genome were sequenced by using the Trugene HIV-1 Genotyping System. The prevalence of transmitted drug resistance was analyzed by using the surveillance drug resistance mutations (SDRM) list recommended by the WHO in 2009. We report findings for 118 of 180 eligible patients (65.6% coverage). SDRM were detected in 26 of 118 patients (22.0%) who were infected with subtype B and belonged mostly to the men having sex with men (MSM). The majority of patients with primary resistance carried SDRM associated with resistance to nucleoside analogues reverse transcriptase inhibitors (NRTIs, 23 of 118 patients, 19.5%). The most frequently found NRTI SDRM was T215S (17 of 118 patients, 14.4%). SDRM associated with resistance to nonnucleoside reverse transcriptase inhibitors were detected in three (2.5%) patients and primary resistance to protease inhibitors was not detected. Non-B subtypes were detected in 13/118 patients (11%). A total of 12 transmission pairs and eight distinct transmission clusters were identified with the largest cluster harboring sequences from 19 patients; among them all but two were carrying the T215S mutation. This study showed a high prevalence of TDR in newly diagnosed MSM from Croatia and is an important contribution concerning the relationship between local transmission clusters and the spread of resistant virus.

Short Communication: Increase of HIV-1 K103N Transmitted Drug Resistance and Its Association with Efavirenz Use in South Korea

“…The increase in NNRTI TDR is important because it is associated with virological failure of first-line ART when suboptimal NNRTI-based regimens are selected for such patients. 15,16 Although there have been some reports about TDR being transmitted within clusters, including K103N, [17][18][19][20][21][22] we identified just three distinctly clustering pairs that were carrying K103N. Taking into account the three described pairs, there were at least five independent K103N TDR strains in our study population, implying multiple sources of K103N transmission.…”

No Difference in Prevalence of Transmitted Drug Resistance between Injection Drug Users and Non-Injection Drug Users: A Cross-Sectional Study among Antiretroviral Treatment-Naïve HIV Patients

“…It has been reported that transmission clusters contribute to the spread of TDR in relatively closed populations [43, 44]. Therefore, a distinct regional HIV-1 subtype distribution as well as relatively closed transmission environment may contribute to the local higher TDR prevalence compared with other places in Guangxi.…”

The emerging and re-emerging human immunodeficiency virus epidemics in Europe

“…The reported prevalence of TDR in Europe in individuals diagnosed with HIV infection since 2005 ranges between 0% and 25%. An important contribution of transmission clusters to the spread of resistant virus (particularly among MSM carrying T215 revertants, and Y181C and M41L mutations) has been described in several countries and regions within countries (Sweden, Denmark, Greenland, Italy, Croatia, northern Greece, the Basque Country in Spain, and Geneva) . Although subtype B infection was a significant predictor of TDR in the SPREAD study and several more recent national studies (Croatia and Italy), other studies have found a comparable risk of TDR in subtype B and non‐subtype B infections (France) .…”

“…However, more recent data on the prevalence of TDR in Europe are available in a number of national and regional studies (Table ) . Analysis of TDR prevalence according to drug classes shows that the majority of surveillance drug resistance mutations observed in newly diagnosed individuals are associated with NRTI resistance . Nevertheless, the prevalence of TDR to NRTIs is below 10% in the majority of European national studies (Table ).…”