Vergne Laurence, Kane Coumba Touré, Laurent Christian, Diakhaté Ndella, Gueye Ndeye Fatou Ngom, Gueye Pape Mandoumbé, Sow Papa Salif, Faye Mame Awa, Liégeois Florian, Ndir Adama, Lanièce Isabelle, Peeters Martine, Ndoye Ibrahima, Mboup Souleymane, Delaporte Eric
Institut de Recherche pour le Développement (IRD, UR 36), University of Montpellier, France.
AIDS. 2003 Jul;17 Suppl 3:S31-8. doi: 10.1097/00002030-200317003-00005.
To monitor the prevalence of antiretroviral (ARV)-resistant HIV-1 viruses, and the genotypic mutations in patients enrolled in the Senegalese initiative for access to antiretroviral treatment (ART).
A total of 80 patients with a virological follow-up of at least 6 months were selected, 68 were ART-naive and 12 ART-experienced. Genotypic resistance to ARV was studied at baseline for a random subset of patients and at each rebound in plasma viral load during ART, by sequencing the protease and reverse transcriptase genes.
At baseline, 66 patients received highly active antiretroviral therapy (HAART) [2 nucleoside reverse transcriptase inhibitors (NRTIs) +1 protease inhibitor (PI) (n = 64) or 2 NRTIs + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) (n = 2)] and 14 patients (17.5%) started with a dual therapy because of ongoing antitubercular therapy or efficient previous bitherapy for the ART-experienced patients. The emergence of drug-resistant viruses (n = 13) during follow-up was more frequent in ART-experienced patients than in ART-naive patients, 41.7 versus 11.8%, resistant viruses emerged at comparable follow-up periods, a median of 17.8 and 18.3 months, respectively. In patients receiving zidovudine and lamivudine in their drug regimen, resistance to lamivudine was more frequent than to zidovudine. Two of the three patients, with viruses resistant to PIs, acquired mutations associated with cross-resistance. Strikingly, five (39%) of the 13 patients developed resistances to drugs that they had never received (n = 3) or that they received 18 or 36 months ago (n = 2). Didanosine/stavudine pressure had selected zidovudine-resistant viruses in four patients, and indinavir had selected a nelfinavir-resistant virus in one patient.
In contrast to other reports from developing countries where patients had received ARVs in an uncontrolled manner, our study showed that implementation of HAART together with good clinical, biological and logistical monitoring can reduce the emergence of resistant strains in Africa.
监测在参与塞内加尔抗逆转录病毒治疗（ART）倡议项目的患者中，抗逆转录病毒（ARV）耐药的HIV-1病毒的流行情况以及基因变异。
共选取80例病毒学随访至少6个月的患者，其中68例为初治患者，12例为经治患者。通过对蛋白酶和逆转录酶基因进行测序，在基线时对部分随机选取的患者以及在ART期间血浆病毒载量每次反弹时研究对ARV的基因耐药性。
基线时，66例患者接受了高效抗逆转录病毒治疗（HAART）[2种核苷类逆转录酶抑制剂（NRTIs）+1种蛋白酶抑制剂（PI）（n = 64）或2种NRTIs + 1种非核苷类逆转录酶抑制剂（NNRTI）（n = 2）]，14例患者（17.5%）因正在进行抗结核治疗或经治患者之前有效的双药治疗而开始接受双药治疗。随访期间耐药病毒（n = 13）的出现，在经治患者中比初治患者更频繁，分别为41.7%和11.8%，耐药病毒在相似的随访期出现，中位数分别为17.8个月和18.3个月。在其药物治疗方案中接受齐多夫定和拉米夫定的患者中，对拉米夫定的耐药比对齐多夫定更常见。3例对PI耐药的患者中有2例获得了与交叉耐药相关的突变。引人注目的是，13例患者中有5例（39%）对他们从未接受过的药物（n = 3）或在18或36个月前接受过的药物（n = 2）产生了耐药。去羟肌苷/司他夫定的压力在4例患者中选择出了对齐多夫定耐药的病毒，茚地那韦在1例患者中选择出了对奈非那韦耐药的病毒。
与发展中国家其他关于患者以不受控制的方式接受ARV的报道不同，我们的研究表明，HAART的实施以及良好的临床、生物学和后勤监测可以减少非洲耐药菌株的出现。
