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泰国 HIV/HBV 共感染患者接受含拉米夫定的高效抗逆转录病毒治疗的长期乙型肝炎病毒(HBV)应答。

Long-term hepatitis B virus (HBV) response to lamivudine-containing highly active antiretroviral therapy in HIV-HBV co-infected patients in Thailand.

机构信息

Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.

出版信息

PLoS One. 2012;7(7):e42184. doi: 10.1371/journal.pone.0042184. Epub 2012 Jul 31.

DOI:10.1371/journal.pone.0042184
PMID:22860080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3409123/
Abstract

BACKGROUND

Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV). In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART) and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known.

METHODOLOGY/PRINCIPAL FINDING: HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030) and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg). At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 log(10) IU/mL and 4.47 log(10) copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24%) lost HBsAg and 7 of 8 (88%) HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months). HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L.

CONCLUSIONS

All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for the management of co-infected patients in resource-limited countries where the vast majority of co-infected patients are currently receiving 3TC.

摘要

背景

约有 400 万人同时感染 HIV 和乙型肝炎病毒(HBV)。在资源有限的环境中,大多数 HIV 感染者接受包含拉米夫定(3TC 类)的一线高效抗逆转录病毒治疗(HAART),但对于 HBV 对包含拉米夫定的 HAART 的长期病毒学反应尚不清楚。

方法/主要发现:本研究纳入了 PHPT 队列(ClinicalTrials.gov NCT00433030)中入组的 HIV-HBV 合并感染患者,并开始接受 3TC 类 HAART 方案。在基线、3 个月、12 个月和之后每 6 个月(最长 5 年)时,测量 HBV-DNA、HIV-RNA、CD4+T 细胞计数和丙氨酸转氨酶。Kaplan-Meier 分析用于估计达到并维持 HBV-DNA 抑制的患者的累积率。在 30 例合并感染患者中,有 19 例 HBeAg 阳性(HBeAg)。在开始 3TC 类 HAART 时,中位 HBV DNA 和 HIV RNA 水平分别为 7.35 log(10)IU/mL 和 4.47 log(10)拷贝/mL。在 12 个月时,67%的患者达到 HBV DNA 抑制:HBeAg 阴性患者 100%,HBeAg 阳性患者 47%。73%的患者 HIV RNA 低于 50 拷贝/mL。在 23 例达到 HBV-DNA 抑制的患者中,HBV-DNA 抑制维持率分别为 91%、87%和 80%,在 1、2 和 4 年时。在 17 例仍在使用 3TC 时维持 HBV-DNA 抑制的患者中,有 4 例(24%)失去 HBsAg,8 例 HBeAg 阳性患者中有 7 例(88%)失去 HBeAg,他们最后一次就诊(中位时间,59 个月)。仅在 HBeAg 阳性患者中观察到 HBV 突破,在 7 例发生 HBV 突破的患者中,有 6 例存在与拉米夫定耐药相关的 rtM204I/V 突变,以及 rtL180M 和/或 rtV173L。

结论

所有 HBeAg 阴性患者和 63%的 HBeAg 阳性 HIV-HBV 合并感染患者在接受包含拉米夫定的 HAART 时达到了长期 HBV DNA 抑制。这项研究提供了在资源有限的国家管理合并感染患者的有用信息,在这些国家中,绝大多数合并感染患者目前正在接受 3TC 治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84e9/3409123/a8942e1e746c/pone.0042184.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84e9/3409123/145364e02e5b/pone.0042184.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84e9/3409123/62c3013dca80/pone.0042184.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84e9/3409123/b99dfc7c11d9/pone.0042184.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84e9/3409123/a8942e1e746c/pone.0042184.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84e9/3409123/145364e02e5b/pone.0042184.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84e9/3409123/62c3013dca80/pone.0042184.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84e9/3409123/b99dfc7c11d9/pone.0042184.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84e9/3409123/a8942e1e746c/pone.0042184.g004.jpg

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