Renwick N, Halaby T, Weverling G J, Dukers N H, Simpson G R, Coutinho R A, Lange J M, Schulz T F, Goudsmit J
Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam, The Netherlands.
AIDS. 1998 Dec 24;12(18):2481-8. doi: 10.1097/00002030-199818000-00018.
The finding of antibodies against human herpesvirus 8 (HHV-8) is associated with the occurrence of Kaposi's sarcoma in persons infected with HIV. However, the predictive value of HHV-8 antibodies for Kaposi's sarcoma in HIV infection is unknown.
The Amsterdam Cohort Studies on HIV infection and AIDS started in 1984 for homosexual men and in 1985 for injecting drug users. Serum samples from 1459 homosexual men and 1167 drug users were tested for antibodies to recombinant HHV-8 lytic-phase capsid (ORF65) antigen and latent-phase nuclear (ORF73) antigen. Individuals were retrospectively identified as HHV-8-positive or HHV-8-negative at enrolment or HHV-8 seroconverter during the study. Kaposi's sarcoma-free survival time was compared between HIV-infected men who were positive for HHV-8 at enrolment and those who later seroconverted for HHV-8. Hazard ratios were estimated for Kaposi's sarcoma, lymphoma, and opportunistic infection according to the HHV-8 serostatus.
The incidence of HHV-8 seroconversion among drugs users was 0.7 per 100 person-years based on 31 seroconversions, whereas an incidence of 3.6 was found among homosexual men based on 215 seroconversions. The hazard ratio for Kaposi's sarcoma was 3.15 (95% CI: 1.89-5.25) in HIV-infected individuals if HHV-8 antibodies were present either at enrolment or at HIV seroconversion. In HIV-infected persons who later seroconverted to HHV-8, Kaposi's sarcoma developed more rapidly: hazard ratio of 5.04 (95% CI: 2.94-8.64), an additional risk of 1.60 (95% CI: 1.01-2.53; P = 0.04). Time-dependent adjustment for CD4+ cell count and HIV RNA had no impact on the additional risk, although the CD4+ cell count was an independent risk factor for Kaposi's sarcoma. HHV-8 infection did not increase the risk of AIDS-related lymphoma or opportunistic infections.
The incidence of HHV-8 infection is higher in homosexual men than in drug users. The presence of HHV-8 antibodies in HIV-infected persons increases the risk of Kaposi's sarcoma. Among HIV-infected persons, those who subsequently seroconvert for HHV-8 are at highest risk. These results strongly confirm the causal role of HHV-8 in Kaposi's sarcoma and emphasize the clinical relevance of HHV-8 seroconversion before and after the HIV infection.
在感染人类免疫缺陷病毒（HIV）的人群中，发现抗人类疱疹病毒8型（HHV-8）抗体与卡波西肉瘤的发生有关。然而，HHV-8抗体对HIV感染中卡波西肉瘤的预测价值尚不清楚。
阿姆斯特丹HIV感染与艾滋病队列研究始于1984年，针对男同性恋者，1985年针对注射吸毒者。对1459名男同性恋者和1167名吸毒者的血清样本进行检测，以检测针对重组HHV-8裂解期衣壳（ORF65）抗原和潜伏期核（ORF73）抗原的抗体。在入组时回顾性确定个体为HHV-8阳性或HHV-8阴性，或在研究期间为HHV-8血清转化者。比较入组时HHV-8呈阳性的HIV感染男性与后来发生HHV-8血清转化的男性的无卡波西肉瘤生存时间。根据HHV-8血清状态估计卡波西肉瘤、淋巴瘤和机会性感染的风险比。
基于31例血清转化，吸毒者中HHV-8血清转化的发生率为每100人年0.7例，而基于215例血清转化，男同性恋者中的发生率为3.6例。在HIV感染个体中，如果在入组时或HIV血清转化时存在HHV-8抗体，卡波西肉瘤的风险比为3.15（95%CI：1.89-5.25）。在后来发生HHV-8血清转化的HIV感染者中，卡波西肉瘤发展得更快：风险比为5.04（95%CI：2.94-8.64），额外风险为1.60（95%CI：1.01-2.53；P=0.04）。对CD4+细胞计数和HIV RNA进行时间依赖性调整对额外风险没有影响，尽管CD4+细胞计数是卡波西肉瘤的独立危险因素。HHV-8感染并未增加与艾滋病相关的淋巴瘤或机会性感染的风险。
男同性恋者中HHV-8感染的发生率高于吸毒者。HIV感染者中HHV-8抗体的存在增加了卡波西肉瘤的风险。在HIV感染者中，随后发生HHV-8血清转化的人风险最高。这些结果有力地证实了HHV-8在卡波西肉瘤中的因果作用，并强调了HIV感染前后HHV-8血清转化的临床相关性。
