title: Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba.
abstract: In Cuba, antiretroviral therapy rollout started in 2001 and antiretroviral therapy coverage has reached almost 40% since then. The objectives of this study were therefore to analyze subtype distribution, and level and patterns of drug resistance in therapy-naive HIV-1 patients. Four hundred and one plasma samples were collected from HIV-1 therapy-naive patients in 2003 and in 2007-2011. HIV-1 drug resistance genotyping was performed in the pol gene and drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, version 2009. Potential impact on first-line therapy response was estimated using genotypic drug resistance interpretation systems HIVdb version 6.2.0 and Rega version 8.0.2. Phylogenetic analysis was performed using Neighbor-Joining. The majority of patients were male (84.5%), men who have sex with men (78.1%) and from Havana City (73.6%). Subtype B was the most prevalent subtype (39.3%), followed by CRF20-23-24_BG (19.5%), CRF19_cpx (18.0%) and CRF18_cpx (10.3%). Overall, 29 patients (7.2%) had evidence of drug resistance, with 4.0% (CI 1.6%-4.8%) in 2003 versus 12.5% (CI 7.2%-14.5%) in 2007-2011. A significant increase in drug resistance was observed in recently HIV-1 diagnosed patients, i.e. 14.8% (CI 8.0%-17.0%) in 2007-2011 versus 3.8% (CI 0.9%-4.7%) in 2003 (OR 3.9, CI 1.5-17.0, p=0.02). The majority of drug resistance was restricted to a single drug class (75.8%), with 55.2% patients displaying nucleoside reverse transcriptase inhibitor (NRTI), 10.3% non-NRTI (NNRTI) and 10.3% protease inhibitor (PI) resistance mutations. Respectively, 20.7% and 3.4% patients carried viruses containing drug resistance mutations against NRTI+NNRTI and NRTI+NNRTI+PI. The first cases of resistance towards other drug classes than NRTI were only detected from 2008 onwards. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). The median genotypic susceptibility score for the commonly prescribed first-line therapies was 2.5. This analysis emphasizes the need to perform additional surveillance studies to accurately assess the level of transmitted drug resistance in Cuba, as the extent of drug resistance might jeopardize effectiveness of first-line regimens prescribed in Cuba and might necessitate the implementation of baseline drug resistance testing.
authors: Virology Department, Institute of Tropical Medicine Pedro Kourí, Havana City, Cuba. lissetteps@infomed.sld.cu
authors: Lissette
authors: L
authors: Pérez
authors: Vivian
authors: V
authors: Kourí
authors: Yoan
authors: Y
authors: Alemán
authors: Yeisel
authors: Y
authors: Abrahantes
authors: Consuelo
authors: C
authors: Correa
authors: Carlos
authors: C
authors: Aragonés
authors: Orlando
authors: O
authors: Martínez
authors: Jorge
authors: J
authors: Pérez
authors: Carlos
authors: C
authors: Fonseca
authors: Jorge
authors: J
authors: Campos
authors: Delmis
authors: D
authors: Álvarez
authors: Yoeri
authors: Y
authors: Schrooten
authors: Nathalie
authors: N
authors: Dekeersmaeker
authors: Stijn
authors: S
authors: Imbrechts
authors: Gertjan
authors: G
authors: Beheydt
authors: Lore
authors: L
authors: Vinken
authors: Yudira
authors: Y
authors: Soto
authors: Alina
authors: A
authors: Álvarez
authors: Anne-Mieke
authors: AM
authors: Vandamme
authors: Kristel
authors: K
authors: Van Laethem
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003462:Cuba / Q000453:epidemiology; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D019380:Anti-HIV Agents