Kully C, Yerly S, Erb P, Kind C, Krautheim A, Perrin L, Rudin C
Department of Pediatrics, University Children's Hospital, CH-4058 Basel, Switzerland.
J Infect Dis. 1999 Mar;179(3):705-8. doi: 10.1086/314615.
In 1994, the Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 demonstrated a two-thirds reduction of perinatal human immunodeficiency virus (HIV) type 1 transmission with zidovudine chemoprophylaxis. However, zidovudine alone does not fully suppress HIV replication, and chemoprophylaxis with zidovudine alone might select for zidovudine-resistant viral variants, decreasing the efficacy of zidovudine prophylaxis and affecting future responses to combined antiretroviral regimens. Sixty-two HIV-infected pregnant women consecutively enrolled in the ongoing Swiss HIV and Pregnancy Study were prospectively evaluated for the presence or development of zidovudine resistance by analysis of codon 215 of the reverse transcriptase gene. Six women (9.6%) harbored a codon T215Y/F mutation, which is associated with high-level resistance to zidovudine. Postnatal evaluation was completed in all children of mothers harboring the mutation. None was HIV-infected. The observed prevalence of codon 215 mutations of 9.6% raises important concerns regarding the future use of the PACTG 076 regimen.
1994年，儿童艾滋病临床试验组（PACTG）的076号方案表明，齐多夫定化学预防可使围产期1型人类免疫缺陷病毒（HIV）传播减少三分之二。然而，单独使用齐多夫定并不能完全抑制HIV复制，仅用齐多夫定进行化学预防可能会选择出对齐多夫定耐药的病毒变异株，降低齐多夫定预防的效果，并影响未来对抗逆转录病毒联合疗法的反应。通过对逆转录酶基因第215密码子的分析，对连续纳入正在进行的瑞士HIV与妊娠研究的62名HIV感染孕妇进行前瞻性评估，以确定是否存在齐多夫定耐药或是否会出现齐多夫定耐药。6名女性（9.6%）携带T215Y/F密码子突变，该突变与对齐多夫定的高水平耐药相关。对所有携带该突变母亲的孩子均完成了产后评估。无一例感染HIV。观察到的第215密码子突变发生率为9.6%，这引发了人们对未来使用PACTG 076方案的重要担忧。
