Makerere University, Johns Hopkins University Research Collaboration, Kampala, Uganda.
AIDS. 2012 Jan 28;26(3):325-33. doi: 10.1097/QAD.0b013e32834e892c.
Nevirapine and cotrimoxazole are associated with hematologic toxicities and skin-rash. Safety of their concurrent use for prophylaxis over extended periods among HIV-exposed uninfected infants has not been previously assessed.
Secondary data analysis of the 'HIV Prevention Trials Network-046 protocol' (version 2.0), a phase-III, randomized, placebo-controlled trial that assessed efficacy and safety of nevirapine prophylaxis against breast milk transmission of HIV-1.
Trial infants received 6-month study nevirapine/placebo, and standard-of-care peripartum single-dose nevirapine+/- zidovudine 'tail', and cotrimoxazole prophylaxis from 6 weeks through breastfeeding cessation. Adverse events were monitored using United States Division of AIDS Toxicity Tables (2004). Risk of neutropenia, anemia and skin-rash in the cotrimoxazole + nevirapine and the cotrimoxazole + placebo groups were compared using negative-binomial regression.
Incidence of neutropenia and/or anemia, and skin-rash was highest during the first 6 weeks of life and declined, thereafter, regardless of study group. Time to first adverse event after 6 weeks was similar in cotrimoxazole + nevirapine and cotrimoxazole + placebo groups: hazard ratio (95% confidence interval) was 1.26 (0.96-1.66) for neutropenia and/or anemia (all grades), 1.27 (0.80-2.03) for neutropenia and/or anemia (grade ≥3) and 1.16 (0.46-2.90) for skin-rash (grade ≥2). There were no statistically significant differences in immediate (6 weeks-6 months) and long-term (6-12 months) adverse event risk among infants on cotrimoxazole + nevirapine versus cotrimoxazole + placebo.
Extended nevirapine and cotrimoxazole prophylaxis through 6 months of age among HIV-exposed uninfected infants did not appear to increase the immediate or long-term risk of neutropenia, anemia or skin-rash. Concurrent use beyond 6 months, however, needs to be evaluated.
奈韦拉平与复方磺胺甲噁唑均与血液学毒性和皮疹有关。此前尚未评估在艾滋病毒暴露的未感染婴儿中同时使用这两种药物进行长期预防的安全性。
对“HIV 预防试验网络-046 方案”（第 2.0 版）的二次数据分析，这是一项 III 期、随机、安慰剂对照试验，评估了奈韦拉平预防方案对 HIV-1 经母乳传播的疗效和安全性。
试验婴儿接受 6 个月的研究用奈韦拉平/安慰剂，以及围产期单次奈韦拉平+/-齐多夫定“尾巴”，并在 6 周龄至停止母乳喂养期间接受复方磺胺甲噁唑预防。使用美国艾滋病毒性表（2004 年）监测不良事件。使用负二项式回归比较复方磺胺甲噁唑+奈韦拉平组和复方磺胺甲噁唑+安慰剂组中性粒细胞减少症、贫血和皮疹的风险。
中性粒细胞减少症和/或贫血和皮疹的发生率在生命的头 6 周内最高，此后则下降，无论研究组如何。6 周后首次出现不良事件的时间在复方磺胺甲噁唑+奈韦拉平组和复方磺胺甲噁唑+安慰剂组相似：中性粒细胞减少症和/或贫血（所有等级）的风险比（95%置信区间）为 1.26（0.96-1.66），中性粒细胞减少症和/或贫血（≥3 级）为 1.27（0.80-2.03），皮疹（≥2 级）为 1.16（0.46-2.90）。在接受复方磺胺甲噁唑+奈韦拉平与复方磺胺甲噁唑+安慰剂的婴儿中，即时（6 周-6 个月）和长期（6-12 个月）不良事件风险没有统计学上的显著差异。
在艾滋病毒暴露的未感染婴儿中，将奈韦拉平与复方磺胺甲噁唑联合预防延长至 6 个月并未增加中性粒细胞减少症、贫血或皮疹的即时或长期风险。然而，需要评估超过 6 个月的联合使用。
