Kuhn Louise, Semrau Katherine, Ramachandran Shobana, Sinkala Moses, Scott Nancy, Kasonde Prisca, Mwiya Mwiya, Kankasa Chipepo, Decker Don, Thea Donald M, Aldrovandi Grace M
Gertrude H. Sergievsky Center, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032-3702, USA.
J Acquir Immune Defic Syndr. 2009 Sep 1;52(1):132-6. doi: 10.1097/QAI.0b013e3181ab6d5e.
Single-dose nevirapine (SDNVP) for prevention of mother-to-child HIV transmission selects mutations conferring resistance to nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy. We investigated mortality and virologic and clinical outcomes after introduction of antiretroviral treatment (ART) among a cohort of women given SDNVP.
When ART programs were introduced in 2004 in Lusaka, Zambia, we were completing a trial of infant feeding, which involved following HIV-infected women who received SDNVP between 2001 and 2005. Women still in follow-up or who could be contacted were evaluated for eligibility for ART (CD4 count <200 or <350 and World Health Organization stage >or=3) and started on NNRTI-based therapy if eligible. We compared mortality in the cohort of women before and after ART access, and examined, among women initiating ART, whether virologic response was better allowing a longer time to elapse between SDNVP and treatment initiation.
In the cohort of 872 women, mortality more than halved after ART became available (relative hazard = 0.46, 95% confidence interval: 0.23 to 0.91, P = 0.03). Of 161 SDNVP-exposed women followed on NNRTI-based ART, 70.8% suppressed (viral load <400 copies/mL). Only 3 of 8 SDNVP-exposed women (37.5%) <6 months of starting therapy suppressed compared with 13 of 22 (59.1%) who started 6-12 months, 44 of 61 (72.1%) 12-24 months, and 54 of 70 (77.1%) >24 months after exposure (chi2 trend P = 0.01).
Most SDNVP-exposed women respond well to NNRTI-based therapy, but there was an attenuation of therapy efficacy that persisted to 12 months after exposure. Women should be screened for ART eligibility during pregnancy and started on effective regimens before delivery.
单剂量奈韦拉平(SDNVP)用于预防母婴HIV传播会选择出对基于非核苷类逆转录酶抑制剂(NNRTI)的治疗产生耐药性的突变。我们调查了在接受SDNVP的一组女性中引入抗逆转录病毒治疗(ART)后的死亡率、病毒学和临床结局。
2004年赞比亚卢萨卡引入ART项目时,我们正在完成一项婴儿喂养试验,该试验涉及对2001年至2005年间接受SDNVP的HIV感染女性进行随访。对仍在随访或能够联系到的女性评估其接受ART的资格(CD4细胞计数<200或<350且世界卫生组织分期≥3期),如果符合条件则开始基于NNRTI的治疗。我们比较了该组女性在获得ART前后的死亡率,并在开始ART的女性中检查病毒学反应是否更好,从而使SDNVP与开始治疗之间的时间间隔更长。
在872名女性队列中,获得ART后死亡率降低了一半以上(相对风险=0.46,95%置信区间:0.23至0.91,P=0.03)。在161名接受基于NNRTI的ART治疗的曾接触SDNVP的女性中,70.8%的病毒得到抑制(病毒载量<400拷贝/毫升)。在开始治疗<6个月的8名曾接触SDNVP的女性中,只有3名(37.5%)病毒得到抑制,而在接触后6 - 12个月开始治疗的22名女性中有13名(59.1%),12 - 24个月开始治疗的61名女性中有44名(72.1%),接触后>24个月开始治疗的70名女性中有54名(77.1%)(趋势χ2检验P=0.01)。
大多数曾接触SDNVP的女性对基于NNRTI的治疗反应良好,但治疗效果在接触后持续12个月出现衰减。应在孕期对女性进行ART资格筛查,并在分娩前开始有效的治疗方案。