Suchergebnisse

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.

Between 1986 and 2011, 100 children have been diagnosed with HIV‐1 in Cuba. 38 have acquired HIV‐1 by vertical transmission, 6 by blood transfusion and 56 by sexual contacts (teenager). Currently, AZT/D4T + 3TC + NVP/KALETRA are available for the treatment of pediatric patients. The aim of the study was to monitor the subtype distribution and emergence of drug resistance in pediatric HIV‐1 infections. Plasma from 46 HIV‐1‐infected children were collected from November 2005 to November 2011, subsequently extracted, amplified and sequenced. Phylogenetic analysis was performed using Mega 4 (Neighbour joining, Kimura 2). The CPR tool v6.0 (WHO list 2009) was used to interpret transmitted drug resistance (TDR). In addition, acquired drug resistance was interpreted according to HIVdb v6.1.1. Experiments were successful for 28 samples from 20 patients (5 patients with multiple samples). At the moment of analysis, 17 children were receiving ART. The median age at diagnosis was 1.9 years, whereas the median age at sampling was 4.5 years. Ten children were male (50%), 16 (80%) were infected by vertical transmission, 1 by blood transfusion (5%) and 3 by sexual route (15%). The subtypes were CRF18_cpx (25%), CRF19_cpx (25%), B (20%), CRF20_BG (10%), G (10%), CRF24_BG (5%) and C (5%). 82.3% of the children who were receiving ART at sampling (14/17) displayed at least one drug resistance mutation. The most common NRTI and NNRT mutations were: M184V (55.5%), T215FY (16.6%) and K70R (16.6%); and K103NS (61.1%) and G190A (22.0%). In contrast, only one PI mutation, L90M (5.5%), was observed. 5.8% of these children displayed single NRTI class resistance, 17.4% single NNRTI class resistance, 59% double NRTI + NNRTI class resistance and 5.8% triple NRTI + NNRTI + PI class resistance. According to HIVdb, NRTI, NNRTI and PI resistance was present in respectively 42.8%, 58.7% and 8.08% of the treated children. High‐level NVP and EFV resistance was observed in 76.5% and 58.8%, respectively. 35.2% displayed already low‐level resistance to ETR/RPV. For NRTI, high‐level resistance to 3TC/FTC was detected in 50%. High‐level resistance to NFV was detected in only one sample. No NNRTI TDR was observed, while one patient displayed PI TDR (L90M) and another NRTI TDR (D67N, T215S and K219Q) (2/11) (18.1%). At this moment, insufficient data is available whether resistance is associated with TDR, poor adherence to treatment or poor efficacy of ART regimens in use. The present study reinforces the usefulness of resistance tests for the correct management of ART.