Absence of genotypic drug resistance and presence of several naturally occurring polymorphisms of human immunodeficiency virus‐1 CRF06_cpx in treatment‐naive patients in Estonia

All non‐B HIV‐1 subtypes and circulating recombinant forms (CRFs) are characterized by several polymorphisms in protease (PR) region. In addition, in recent years the increasing use of antiretroviral treatment (ART) has rapidly raised the spread of transmitted drug resistance. We aimed to determine the presence of naturally occurring polymorphisms and transmitted drug resistance mutations (DRMs) in ART naïve HIV‐1‐positive subjects in Estonia. A total of 115 drug‐naive HIV‐1‐infected subjects (mean age 27 years; 70% male; 65% infected via intravenous drug use and 34% by heterosexual contact) were enrolled. Viral genomic RNA from plasma was directly sequenced in PR, revertase (RT), and envelope (env) regions. Phylogenetic analysis of RT and env regions revealed that 89% and 3% of sequenced viruses belonged to CRF06_cpx and subtype A1, respectively, and 6% were described as unique recombinants (signed A1‐06) between CRF06_cpx and subtype A1 viruses. No primary DRMs were found in PR or RT regions indicating the absence of transmitted drug resistance. The most common polymorphisms in the PR region were K14R, M36I, H69K, and L89M seen in 96%, 100%, 99%, and 100%, respectively. The clinical relevance of these polymorphisms in terms of success of ART has to be monitored in future clinical studies. J. Med. Virol. 81:953–958, 2009. © 2009 Wiley‐Liss, Inc.     

The SnoB study: frequency of baseline raltegravir resistance mutations prevalence in different non-B subtypes

The SnoB study analysed the variability of the integrase (IN) gene of non-B viruses from treatment-na?ve patients to determine whether non-B subtypes carry natural resistance mutations to raltegravir (RAL). Plasma viral RNA from 427 patients was gained, and IN sequences were subtyped and screened for subtype-specific highly-variable residues. Seven viruses of different subtypes were phenotypically tested for RAL susceptibility; 359/427 samples could be sequenced. One hundred and seventy samples (47%) were classified as non-B subtypes. No primary RAL resistance-associated mutations (RRAMs) were detected. Certain secondary mutations were found, mostly related to specific non-B subtypes. L74 M was significantly more prevalent in subtype 02_AG, T97A in A and 06_cpx, V151I in 06_cpx, and G163R in 12_BF. Various additional mutations were also detected and could be associated with the subtype too. While K156 N and S230 N were correlated with B subtype, V72I, L74I, T112I, T125A, V201I and T206S were more frequent in certain non-B subtypes. The resistance factors (RF) of 7 viral strains of different subtypes ranged from 1.0 to 1.9. No primary or secondary but subtype-associated additional RRAMs were present. No correlation between RF and additional RRAMs was found. The prevalence of RRAMs was higher in non-B samples. However, the RFs for the analysed non-B subtypes showed lower values to those reported relevant to clinical failure. As the role of baseline secondary and additional mutations on RAL therapy failure is actually not known, baseline IN screening is necessary.     

Characterization of drug resistance mutations in naïve and ART-treated patients infected with HIV-1 in Yaounde, Cameroon

Currently the prevalence of HIV‐1 infection in Cameroon is 5.1%, CRF02_AG subtype is responsible for about 50% of infections. Since an HIV‐1 drug resistance test is not yet available widely, accurate data on the prevalence of resistant viral strains are missing. The objective of this study was to determine HIV‐1 genetic diversity and to characterize HIV‐1 mutations conferring drug resistance among antiretroviral therapy (ART)‐naïve and ART‐treated patients. A cohort of 239 patients infected with HIV were followed‐up between January 2007 and July 2010 in Cameroon. Two hundred and sixteen plasma samples were sequenced for phylogenetic analysis and identification of drug resistance mutations in the HIV‐1 pol region. A significant genetic diversity was found: Seven pure subtypes (A1, A3, D, F1, F2, G, H), nine circulating recombinant forms (CRFs: 01_AE, 02_AG, 06cpx, 09cpx, 11cpx, 13cpx, 16cpx, 18cpx, 37cpx) and one new unique recombinant form (URF) (G/F2). The rate of transmitted drug resistance (TDR) in naïve patients was 8.2% (4/49). Around 80% of patients failing a first‐line ART harbored a virus with at least one resistance mutation to two antiretroviral (ARV) classes, and 36% of those failing a second‐line regimen carried a virus with at least one resistant mutation to three ARV classes. The high level of drug resistance observed in the cohort is alarming because this occurred as a result of only few years of treatment. Adherence to therapy, adequate education of physicians, and the appropriate use of genotypic resistance assay are critical points of intervention for the improvement of patient care. J. Med. Virol. 84:721–727, 2012. © 2012 Wiley Periodicals, Inc.     

北京市2006年新确认HIV-1感染者耐药突变的流行性研究

目的 研究北京市2006年新确认HIV-1感染者毒株的耐药突变本底数据.方法 随机选取北京市2006年新确认HIV-1感染者抗凝全血标本50份,提取血浆病毒RNA,用逆转录聚合酶链反应扩增HIV-1 pol区基因片段,并进行序列测定及耐药基因型分析.结果 成功扩增出34份标本的pol区基因;在1例样本的蛋白酶编码区检测出1个主要耐药突变,7例样本检测出7个次要耐药突变,主要耐药突变为M46L,毒株是CRF01_AE亚型,次要耐药突变有4种,出现的频率分别为A71T(2个)、A71V(3个)、Q58E(1个)、V11IV(1个).在14例样本逆转录酶编码区检测出一种或多种核苷类和(或)非核苷类逆转录酶抑制剂耐药突变,9例标本检出核苷类逆转录酶抑制剂耐药突变,出现频率分别为:V118I(42.9%)、M184V(7.1%)、A62V(7.1%)、K70T(7.1%)、K65R(7.1%)、K219N(7.1%)、T69d(7.1%)、V75LV(7.1%)、K219R(7.1%);10例标本检出核苷类逆转录酶抑制剂耐药突变,出现的频率分别为V1061(35.5%)、Y181C(15.4%)、K103KR(7.7%)、K103R(7.7%)、L100LV(7.7%)、V1081(7.7%)、V179D(7.7%)、V179DV(7.7%).结论 北京市2006年新确认HIV-1感染者毒株中已经存在一定比例耐药突变,有必要定期进行耐药性监测研究.