Looker Katharine J, Elmes Jocelyn A R, Gottlieb Sami L, Schiffer Joshua T, Vickerman Peter, Turner Katherine M E, Boily Marie-Claude
School of Social and Community Medicine, University of Bristol, Bristol, UK.
Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
Lancet Infect Dis. 2017 Dec;17(12):1303-1316. doi: 10.1016/S1473-3099(17)30405-X. Epub 2017 Aug 23.
HIV and herpes simplex virus type 2 (HSV-2) infections cause a substantial global disease burden and are epidemiologically correlated. Two previous systematic reviews of the association between HSV-2 and HIV found evidence that HSV-2 infection increases the risk of HIV acquisition, but these reviews are now more than a decade old.
For this systematic review and meta-analysis, we searched PubMed, MEDLINE, and Embase (from Jan 1, 2003, to May 25, 2017) to identify studies investigating the risk of HIV acquisition after exposure to HSV-2 infection, either at baseline (prevalent HSV-2 infection) or during follow-up (incident HSV-2 infection). Studies were included if they were a cohort study, controlled trial, or case-control study (including case-control studies nested within a cohort study or clinical trial); if they assessed the effect of pre-existing HSV-2 infection on HIV acquisition; and if they determined the HSV-2 infection status of study participants with a type-specific assay. We calculated pooled random-effect estimates of the association between prevalent or incident HSV-2 infection and HIV seroconversion. We also extended previous investigations through detailed meta-regression and subgroup analyses. In particular, we investigated the effect of sex and risk group (general population vs higher-risk populations) on the relative risk (RR) of HIV acquisition after prevalent or incident HSV-2 infection. Higher-risk populations included female sex workers and their clients, men who have sex with men, serodiscordant couples, and attendees of sexually transmitted infection clinics.
We identified 57 longitudinal studies exploring the association between HSV-2 and HIV. HIV acquisition was almost tripled in the presence of prevalent HSV-2 infection among general populations (adjusted RR 2·7, 95% CI 2·2-3·4; number of estimates [N]=22) and was roughly doubled among higher-risk populations (1·7, 1·4-2·1; N=25). Incident HSV-2 infection in general populations was associated with the highest risk of acquisition of HIV (4·7, 2·2-10·1; N=6). Adjustment for confounders at the study level was often incomplete but did not significantly affect the results. We found moderate heterogeneity across study estimates, which was explained by risk group, world region, and HSV-2 exposure type (prevalent vs incident).
We found evidence that HSV-2 infection increases the risk of HIV acquisition. This finding has important implications for management of individuals diagnosed with HSV-2 infection, particularly for those who are newly infected. Interventions targeting HSV-2, such as new HSV vaccines, have the potential for additional benefit against HIV, which could be particularly powerful in regions with a high incidence of co-infection.
World Health Organization.
HIV和2型单纯疱疹病毒（HSV-2）感染造成了巨大的全球疾病负担，且在流行病学上存在关联。之前两项关于HSV-2与HIV关联的系统评价发现，有证据表明HSV-2感染会增加感染HIV的风险，但这些评价距今已有十多年。
对于这项系统评价和荟萃分析，我们检索了PubMed、MEDLINE和Embase（2003年1月1日至2017年5月25日），以识别调查在基线时（HSV-2现患感染）或随访期间（HSV-2新发感染）暴露于HSV-2感染后感染HIV风险的研究。纳入的研究需为队列研究、对照试验或病例对照研究（包括嵌套在队列研究或临床试验中的病例对照研究）；需评估既往HSV-2感染对感染HIV的影响；需使用型特异性检测方法确定研究参与者的HSV-2感染状态。我们计算了HSV-2现患或新发感染与HIV血清转换之间关联的合并随机效应估计值。我们还通过详细的荟萃回归和亚组分析扩展了之前的研究。特别是，我们调查了性别和风险组（一般人群与高风险人群）对HSV-2现患或新发感染后感染HIV的相对风险（RR）的影响。高风险人群包括女性性工作者及其客户、男男性行为者、血清学不一致的夫妇以及性传播感染诊所的就诊者。
我们识别出57项探索HSV-2与HIV关联的纵向研究。在一般人群中，存在HSV-2现患感染时感染HIV的几率几乎增加两倍（调整后RR 2.7，95%CI 2.2 - 3.4；估计值数量[N]=22），在高风险人群中大约增加一倍（1.7，1.4 - 2.1；N=25）。一般人群中的HSV-2新发感染与感染HIV的最高风险相关（4.7，2.2 - 10.1；N=6）。在研究层面进行混杂因素调整往往不完整，但未显著影响结果。我们发现研究估计值之间存在中度异质性，这可由风险组、世界区域和HSV-2暴露类型（现患与新发）来解释。
我们发现有证据表明HSV-2感染会增加感染HIV的风险。这一发现对于诊断为HSV-2感染的个体的管理具有重要意义，尤其是对于新感染的个体。针对HSV-2的干预措施，如新的HSV疫苗，有可能对HIV带来额外益处，这在合并感染高发地区可能尤为有效。
世界卫生组织。
