BMC Infectious Diseases | |
Herpes simplex virus type 2 and HIV disease progression: a systematic review of observational studies | |
Sharon Lynn Walmsley2  Prakesh Shah3  Kellie Murphy1  Darrell Hoi-San Tan2  | |
[1] Department of Maternal Fetal Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada;Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College St., Suite 425, Toronto, ON M5T 3M6, Canada;Department of Pediatrics, University of Toronto, 600 University Ave., Room 775-A, Toronto, ON M5G 1X5, Canada | |
关键词: Systematic review; Seropositivity; CD4 count; Viral load; Disease progression; Human immunodeficiency virus; Herpes simplex virus; | |
Others : 1145671 DOI : 10.1186/1471-2334-13-502 |
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received in 2013-04-26, accepted in 2013-10-21, 发布年份 2013 | |
【 摘 要 】
Background
Herpes simplex virus type 2 (HSV-2) is a common co-infection among HIV-infected adults that is hypothesized to accelerate HIV disease progression.
Methods
We searched Medline, EMBASE, relevant conference proceedings (2006–12) and bibliographies of identified studies without language restriction for cohort studies examining the impact of HSV-2 on highly active antiretroviral therapy-untreated HIV disease in adults. The exposure of interest was HSV-2 seropositivity or clinical/laboratory markers of HSV-2 activity. The primary outcome was HIV disease progression, defined as antiretroviral initiation, development of AIDS/opportunistic infection, or progression to CD4 count thresholds (≤200 or ≤350 cells/mm3). Secondary outcomes included HIV plasma viral load and CD4 count.
Results
Seven studies were included. No definitive relationship was observed between HSV-2 seropositivity and time to antiretroviral initiation (n=2 studies), CD4≤350 (n=1), CD4≤200 (n=1), death (n=1), viral load (n=6) or CD4 count (n=3). Although two studies each observed trends towards accelerated progression to clinical AIDS/opportunistic infection in HSV-2 seropositives, with pooled unadjusted hazard ratio=1.85 (95% CI=1.12,3.06; I2=2%), most OIs observed in the study for which data were available can occur at high CD4 counts and may not represent HIV progression. In contrast, a single study HSV-2 disease activity found that the presence of genital HSV-2 DNA was associated with a 0.4 log copies/mL increase in HIV viral load.
Conclusions
Despite an observation that HSV-2 activity is associated with increased HIV viral load, definitive evidence linking HSV-2 seropositivity to accelerated HIV disease progression is lacking. The attenuating effects of acyclovir on HIV disease progression observed in recent trials may result both from direct anti-HIV activity as well as from indirect benefits of HSV-2 suppression.
【 授权许可】
2013 Tan et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
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20150402142753847.pdf | 278KB | download | |
Figure 2. | 15KB | Image | download |
Figure 1. | 54KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
【 参考文献 】
- [1]Romanowski B, Myziuk LN, Walmsley SL, Trottier S, Singh AE, Houston S, Joffe M, Chiu I: Seroprevalence and risk factors for Herpes Simplex virus infection in a population of HIV-infected patients in Canada. Sex Transm Dis 2008, 36:165-169.
- [2]Gray RH, Li X, Wawer MJ, Serwadda D, Sewankambo NK, Wabwire-Mangen F, Lutalo T, Kiwanuka N, Kigozi G, Nalugoda F, et al.: Determinants of HIV-1 load in subjects with early and later HIV infections, in a general-population cohort of Rakai, Uganda. J Infect Dis 2004, 189:1209-1215.
- [3]Lyles RH, Munoz A, Yamashita TE, Bazmi H, Detels R, Rinaldo CR, Margolick JB, Phair JP, Mellors JW: Natural history of human immunodeficiency virus type 1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men. Multicenter AIDS Cohort Study. J Infect Dis 2000, 181:872-880.
- [4]Strick LB, Wald A, Celum C: Management of herpes simplex virus type 2 infection in HIV type 1-infected persons. Clin Infect Dis 2006, 43:347-356.
- [5]Reynolds SJ, Makumbi F, Newell K, Kiwanuka N, Ssebbowa P, Mondo G, Boaz I, Wawer MJ, Gray RH, Serwadda D, et al.: Effect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-controlled trial. Lancet Infect Dis 2012, 12:441-448.
- [6]Lingappa JR, Baeten JM, Wald A, Hughes JP, Thomas KK, Mujugira A, Mugo N, Bukusi EA, Cohen CR, Katabira E, et al.: Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial. Lancet 2010, 375:824-833.
- [7]McMahon MA, Siliciano JD, Lai J, Liu JO, Stivers JT, Siliciano RF, Kohli RM: The antiherpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multidrug resistance mutation. J Biol Chem 2008, 283:31289-31293.
- [8]Lisco A, Vanpouille C, Tchesnokov EP, Grivel JC, Biancotto A, Brichacek B, Elliott J, Fromentin E, Shattock R, Anton P, et al.: Acyclovir is activated into a HIV-1 reverse transcriptase inhibitor in herpesvirus-infected human tissues. Cell Host Microbe 2008, 4:260-270.
- [9]von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 2007, 147:573-577.
- [10]Vandenbroucke JP, von Elm E, Altman DG, Gotzsche PC, Mulrow CD, Pocock SJ, Poole C, Schlesselman JJ, Egger M: Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Ann Intern Med 2007, 147:W163-W194.
- [11]Sanderson S, Tatt ID, Higgins JP: Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography. Int J Epidemiol 2007, 36:666-676.
- [12]Barnabas RV, Wasserheit JN, Huang Y, Janes H, Morrow R, Fuchs J, Mark KE, Casapia M, Mehrotra DV, Buchbinder SP, et al.: Impact of herpes simplex virus type 2 on HIV-1 acquisition and progression in an HIV vaccine trial (the Step study). J Acquir Immune Defic Syndr 2011, 57:238-244.
- [13]Cachay ER, Frost SDW, Richman DD, Smith DM, Little SJ: Herpes simplex virus type 2 infection does not influence viral dynamics during early HIV-1 infection [see comment]. J Infect Dis 2007, 195:1270-1277.
- [14]Cachay ER, Frost SDW, Poon AFY, Looney D, Rostami SM, Pacold ME, Richman DD, Little SJ, Smith DM: Herpes simplex virus type 2 acquisition during recent HIV infection does not influence plasma HIV levels. J Acquir Immune Defic Syndr 2008, 47:592-596.
- [15]Crum-Cianflone N, Hale B, Truett A, Utz G, Chun H, Pope B, Burgi A, Medina S, Brandt C, Furtek K, et al.: The effect of herpes simplex virus 2 (HSV2) co-infection in HIV-infected persons on CD4 counts, HIV viral load, and time to antiretroviral medications. In 44th Annual Meeting of IDSA: 12-15 October 2006; Abstract 895. Toronto, Canada: Alexandria: Infectious Diseases Society of America; 2006.
- [16]Nagot N, Ouedraogo A, Konate I, Weiss HA, Foulongne V, Defer MC, Sanon A, Becquart P, Segondy M, Sawadogo A, et al.: Roles of clinical and subclinical reactivated herpes simplex virus type 2 infection and human immunodeficiency virus type 1 (HIV-1)-induced immunosuppression on genital and plasma HIV-1 levels. J Infect Dis 2008, 198:241-249.
- [17]Roxby AC, Drake AL, John-Stewart G, Brown ER, Matemo D, Otieno PA, Farquhar C: Herpes simplex virus type 2, genital ulcers and HIV-1 disease progression in postpartum women. PLoS One 2011, 6:e19947.
- [18]Suligoi B, Dorrucci M, Volpi A, Andreoni M, Pezzotti P, Rezza G, Italian Seroconversion S: Absence of an effect of herpes simplex virus type 2 infection on HIV disease progression: data from a cohort of HIV-positive individuals with known date of seroconversion. AIDS 2001, 15:133-135.
- [19]Ludema C, Cole SR, Poole C, Chu H, Eron JJ: Meta-analysis of randomized trials on the association of prophylactic acyclovir and HIV-1 viral load in individuals coinfected with herpes simplex virus-2. AIDS 2011, 25:1265-1269.
- [20]Ioannidis JP, Collier AC, Cooper DA, Corey L, Fiddian AP, Gazzard BG, Griffiths PD, Contopoulos-Ioannidis DG, Lau J, Pavia AT, et al.: Clinical efficacy of high-dose acyclovir in patients with human immunodeficiency virus infection: a meta-analysis of randomized individual patient data. J Infect Dis 1998, 178:349-359.
- [21]Ashley-Morrow R, Krantz E, Wald A: Time course of seroconversion by HerpeSelect ELISA after acquisition of genital herpes simplex virus type 1 (HSV-1) or HSV-2. Sex Transm Dis 2003, 30:310-314.
- [22]Ashley RL, Militoni J, Lee F, Nahmias A, Corey L: Comparison of Western blot (immunoblot) and glycoprotein G-specific immunodot enzyme assay for detecting antibodies to herpes simplex virus types 1 and 2 in human sera. J Clin Microbiol 1988, 26:662-667.
- [23]Ramaswamy M, Sabin C, McDonald C, Smith M, Taylor C, Geretti AM: Herpes simplex virus type 2 (HSV-2) seroprevalence at the time of HIV-1 diagnosis and seroincidence after HIV-1 diagnosis in an ethnically diverse cohort of HIV-1-infected persons. Sex Transm Dis 2006, 33:96-101.
- [24]Benedetti J, Corey L, Ashley R: Recurrence rates in genital herpes after symptomatic first-episode infection. Ann Intern Med 1994, 121:847-854.
- [25]Benedetti JK, Zeh J, Corey L: Clinical reactivation of genital herpes simplex virus infection decreases in frequency over time. Ann Intern Med 1999, 131:14-20.
- [26]Engelberg R, Carrell D, Krantz E, Corey L, Wald A: Natural history of genital herpes simplex virus type 1 infection. Sex Transm Dis 2003, 30:174-177.
- [27]Wald A, Zeh J, Selke S, Ashley RL, Corey L: Virologic characteristics of subclinical and symptomatic genital herpes infections. N Engl J Med 1995, 333:770-775.
- [28]Mole L, Ripich S, Margolis D, Holodniy M: The impact of active herpes simplex virus infection on human immunodeficiency virus load. J Infect Dis 1997, 176:766-770.
- [29]Aumakhan B, Gaydos CA, Quinn TC, Beyrer C, Benning L, Minkoff H, Merenstein DJ, Cohen M, Greenblatt R, Nowicki M, et al.: Clinical reactivations of herpes simplex virus type 2 infection and human immunodeficiency virus disease progression markers. PLoS One 2010, 5:1-7.
- [30]Mugwanya K, Baeten JM, Mugo NR, Irungu E, Ngure K, Celum C: High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial. J Infect Dis 2011, 204:1912-1917.
- [31]Baeten JM, Lingappa J, Beck I, Frenkel LM, Pepper G, Celum C, Wald A, Fife KH, Were E, Mugo N, et al.: Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. J Infect Dis 2011, 203:117-121.
- [32]Roxby AC, Liu AY, Drake AL, Kiarie JN, Richardson B, Lohman-Payne BL, John-Stewart GC, Wald A, De Rosa S, Farquhar C: Short communication: T cell activation in HIV-1/herpes simplex virus-2-coinfected Kenyan women receiving valacyclovir. AIDS Res Hum Retroviruses 2013, 29:94-98.
- [33]Yi TJ, Walmsley S, Szadkowski L, Raboud J, Rajwans N, Shannon B, Kumar S, Kain KC, Kaul R, Tan DHS: A randomized controlled pilot trial of valacyclovir for attenuating inflammation and immune activation in HIV/Herpes simplex virus 2-coinfected adults on suppressive antiretroviral therapy. Clin Infect Dis 2013. epub ahead of print
- [34]Ashley-Morrow R, Nollkamper J, Robinson NJ, Bishop N, Smith J: Performance of focus ELISA tests for herpes simplex virus type 1 (HSV-1) and HSV-2 antibodies among women in ten diverse geographical locations. Clin Microbiol Infect 2004, 10:530-536.