Antiretroviral drug resistance in HIV‐1 therapy‐naïve patients in Cuba, 2006–2011

Abstract

In 2009, genotypic drug resistance testing was introduced for HIV‐1 patients failing antiviral therapy in Cuba. The high prevalence of drug resistance in this population indicated the need for surveillance of transmitted drug resistance (TDR) in therapy‐naïve patients. Therefore, the objectives of this study were to analyze the level and patterns of TDR and subtype in therapy‐naïve HIV‐1 patients in Cuba from 2006 to 2011, and to compare it with reported data from 2004 that indicated 4% TDR, solely restricted to NRTI. 153 plasma from HIV‐1 therapy‐naïve patients were collected between June 2006 and December 2011 and subsequently extracted, amplified and sequenced. Drug resistance was interpreted according to HIVdb v.6.1.1 and WHO list for TDR surveillance (2009) using the CPR tool v.6.0. Phylogenetic analysis was performed using Neighbour Joining (Kimura 2) in Mega 4. The majority of patients was male (82.4%), MSM (68.6%) and originated from Havana province (68.1%). 8.4% were recent infections. Subtype B was the most prevalent subtype (31.3%) followed by CRF20‐23‐24_BG (28.1%), CRF19 (18.3%) and CRF18 (13.0%). The prevalence of subtype B declined from 43.7% in the 2004 study to 31.3% in the present study, whereas BG recombinants increased from 14.4% to 28.1%. Overall, 12.4% (19/154) had evidence of TDR. 3.9% carried at least one NRTI, 1.9% at least one NNRTI and 1.9% at least one PI mutation. Drug resistance mutations against both NRTI and NNRTI were observed in 3.9%, whereas triple class resistance was found in only 0.6%. The most frequent NRTI mutations were M184V (55.5%), T215F/Y/rev (16.6%) and K70R (16.6%). The most frequent NNRTI mutations were K103N (61.1%) and G190A (22.2%). The most common PI mutation was L90M (5.5%). From the 19 patients with TDR, 13 (68.4%) were diagnosed with a recent HIV‐1 infection. AZT/D4T + 3TC + NVP may be effective in 6 of the patients with TDR (31.5%), partially effective in 6 (31.5%) and ineffective in 7 (36.8%). AZT/D4T + 3TC + IDV would be effective in 9 of the patients with TDR (47.3%), partially effective in 8 (42.1%) and ineffective in 2 (10.5%). This analysis confirmed the further expansion of BG recombinants in Cuba and revealed that antiretroviral drug resistance in HIV‐1 therapy‐naïve patients has increased to 12.4% in 2006–2011. The current study emphasizes the need to perform surveillance studies for TDR in therapy‐naïve patients, as the extent of TDR might jeopardize the effectiveness of first‐line regimens prescribed in Cuba.