Human Herpesviruses as Copathogens of HIV Infection, Their Role in HIV Transmission, and Disease Progression

ABSTRACT

Of eight human herpesviruses (HHVs), often, only herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) find mention in medical literature as both of these viruses are commonly associated with genital lesions and oral ulcers, commonly known as cold sores. However, role of human herpesviruses as copathogens and in aggravation and in the transmission of other human diseases, especially the Acquired immunodeficiency syndrome (HIV/AIDS) has only very recently been recognized. Therefore, screening and treating subclinical HHV infections may offer slowing of HIV infection, disease progression, and its transmission. Beside HSV-1 and HSV-2, HHV-3 a causative agent of herpes zoster remained one of the first manifestations of HIV disease before the era of highly active antiretroviral therapy (HAART). HHV-5 also known as human Cytomegalovirus infection remains a significant risk factor for HIV-associated mortality and morbidity even in HAART era. It is proposed that Cytomegalovirus viremia could be a better predictor of HIV disease progression than CD4+ T-lymphocyte count. The role of HHV-4 or Epstein–Burr virus and HHV-6, HHV-7, and HHV-8 is still being investigated in HIV disease progression. This review provides insight into the current understanding about these 8 HHVs, their co-pathogenesis, and role in HIV/ AIDS disease progression. The review also covers recent literature in favor and against administering anti-HHV treatment along with HAART for slower AIDS progression and interrupted sexual transmission.

Key words

Acquired immunodeficiency syndrome - blood - Cytomegalovirus - herpesviruses - highly active antiretroviral therapy - human immunodeficiency virus - semen - transmission

Publikationsverlauf

Artikel online veröffentlicht:
19. April 2020

• REFERENCES

• 1 Røttingen JA, Cameron DW, Garnett GP. A systematic review of the epidemiologic interactions between classic sexually transmitted diseases and HIV: How much really is known? Sex Transm Dis 2001;28:579-97.
• 2 Bock P, Beyers N, Fidler S. Balancing the need to rapidly scale-up and improve clinical outcomes in antiretroviral programmes in developing countries: Lessons from an Indian programmatic cohort study. Trans R Soc Trop Med Hyg 2014;108:599-600.
• 3 Kumarasamy N, Vallabhaneni S, Flanigan TP, Mayer KH, Solomon S. Clinical profile of HIV in India. Indian J Med Res 2005;121:377-94.
• 4 Redhu NS, Dey A, Balooni V, Singh S. Leishmania-HIV co-infection: An emerging problem in India. AIDS 2006;20:1213-5.
• 5 Johnson LF, Lewis DA. The effect of genital tract infections on HIV-1 shedding in the genital tract: A systematic review and meta-analysis. Sex Transm Dis 2008;35:946-59.
• 6 Galvin SR, Cohen MS. The role of sexually transmitted diseases in HIV transmission. Nat Rev Microbiol 2004;2:33-42.
• 7 Barnabas RV, Wasserheit JN, Huang Y, Janes H, Morrow R, Fuchs J, 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;57:238-44.
• 8 Corey L, Wald A, Celum CL, Quinn TC. The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: A review of two overlapping epidemics. J Acquir Immune Defic Syndr 2004;35:435-45.
• 9 Mofenson LM, Brady MT, Danner SP, Dominguez KL, Hazra R, Handelsman E, et al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep 2009;58:1-166.
• 10 Fauci AS, Pantaleo G, Stanley S, Weissman D. Immunopathogenic mechanisms of HIV infection. Ann Intern Med 1996;124:654-63.
• 11 Cohen OJ, Kinter A, Fauci AS. Host factors in the pathogenesis of HIV disease. Immunol Rev 1997;159:31-48.
• 12 Barré-Sinoussi F, Ross AL, Delfraissy JF. Past, present and future: 30 years of HIV research. Nat Rev Microbiol 2013;11:877-83.
• 13 Falster K, Choi JY, Donovan B, Duncombe C, Mulhall B, Sowden D, et al. AIDS-related and non-AIDS-related mortality in the Asia-Pacific region in the era of combination antiretroviral treatment. AIDS 2009;23:2323-36.
• 14 Samuel R, Bettiker RL, Suh B. AIDS related opportunistic infections, going but not gone. Arch Pharm Res 2002;25:215-28.
• 15 Lisco A, Vanpouille C, Margolis L. Coinfecting viruses as determinants of HIV disease. Curr HIV/AIDS Rep 2009;6:5-12.
• 16 Grossman Z, Meier-Schellersheim M, Paul WE, Picker LJ. Pathogenesis of HIV infection: What the virus spares is as important as what it destroys. Nat Med 2006;12:289-95.
• 17 Chakraborty H, Sen PK, Helms RW, Vernazza PL, Fiscus SA, Eron JJ, et al. Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: A probabilistic empiric model. AIDS 2001;15:621-7.
• 18 Cohen MS. HIV and sexually transmitted diseases: Lethal synergy. Top HIV Med 2004;12:104-7.
• 19 Mayer KH, Venkatesh KK. Interactions of HIV, other sexually transmitted diseases, and genital tract inflammation facilitating local pathogen transmission and acquisition. Am J Reprod Immunol 2011;65:308-16.
• 20 Chan DJ, McNally L, Batterham M, Smith DE. Relationship between HIV-RNA load in blood and semen in antiretroviral-naïve and experienced men and effect of asymptomatic sexually transmissible infections. Curr HIV Res 2008;6:138-42.
• 21 Ping LH, Cohen MS, Hoffman I, Vernazza P, Seillier-Moiseiwitsch F, Chakraborty H, et al. Effects of genital tract inflammation on human immunodeficiency virus type 1 V3 populations in blood and semen. J Virol 2000;74:8946-52.
• 22 Kaul R, Pettengell C, Sheth PM, Sunderji S, Biringer A, MacDonald K, et al. The genital tract immune milieu: An important determinant of HIV susceptibility and secondary transmission. J Reprod Immunol 2008;77:32-40.
• 23 Pilcher CD, Joaki G, Hoffman IF, Martinson FE, Mapanje C, Stewart PW, et al. Amplified transmission of HIV-1: Comparison of HIV-1 concentrations in semen and blood during acute and chronic infection. AIDS 2007;21:1723-30.
• 24 Lisco A, Munawwar A, Introini A, Vanpouille C, Saba E, Feng X, et al. Semen of HIV-1-infected individuals: Local shedding of herpesviruses and reprogrammed cytokine network. J Infect Dis 2012;205:97-105.
• 25 Suligoi B, Dorrucci M, Uccella I, Andreoni M, Rezza G; Italian Seroconversion Study. Effect of multiple herpesvirus infections on the progression of HIV disease in a cohort of HIV seroconverters. J Med Virol 2003;69:182-7.
• 26 Adjei AA, Armah HB, Gbagbo F, Boamah I, Adu-Gyamfi C, Asare I. Seroprevalence of HHV-8, CMV, and EBV among the general population in Ghana, West Africa. BMC Infect Dis 2008;8:111.
• 27 Roizman B. Herpesviridae. In: Fields BN, Knipe DM, Howley PM, editors. Fields Virology, Philadelphia, Pa.: Lippincott-Raven; 1996. p. 2221-30.
• 28 Mettenleiter TC, Klupp BG, Granzow H. Herpesvirus assembly: An update. Virus Res 2009;143:222-34.
• 29 Davison AJ. Herpesvirus systematics. Vet Microbiol 2010;143:52-69.
• 30 Davison AJ. Overview of classification. In: Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, et al, editors. Human 1, Herpesviruses. Ch. 1. Cambridge: Cambridge University Press; 2007. pp 1-8. Available at http://www.ncbi.nlm.nih.gov/books/NBK47375/?report=reader. [Last accessed on 2016 Feb 03].
• 31 Pellet PE, Roizmann B. Field Virology. 5^th ed., Vol. 2. New York: Lippencott-Raven; 2007. p. 2479-500.
• 32 Virgin HW, Wherry EJ, Ahmed R. Redefining chronic viral infection. Cell 2009;138:30-50.
• 33 Lisco A, Vanpouille C, Margolis L. War and peace between microbes: HIV-1 interactions with coinfecting viruses. Cell Host Microbe 2009;6:403-8.
• 34 Reynolds SJ, Quinn TC. Developments in STD/HIV interactions: The intertwining epidemics of HIV and HSV-2. Infect Dis Clin North Am 2005;19:415-25.
• 35 Rebbapragada A, Wachihi C, Pettengell C, Sunderji S, Huibner S, Jaoko W, et al. Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract. AIDS 2007;21:589-98.
• 36 Root-Bernstein RS, Hobbs SH. Does HIV "piggyback" on CD4-like surface proteins of sperm, viruses, and bacteria? Implications for co-transmission, cellular tropism and the induction of autoimmunity in AIDS. J Theor Biol 1993;160:249-64.
• 37 Biancotto A, Iglehart SJ, Vanpouille C, Condack CE, Lisco A, Ruecker E, et al. HIV-1 induced activation of CD4+T cells creates new targets for HIV-1 infection in human lymphoid tissue ex vivo. Blood 2008;111:699-704.
• 38 Leach CT, Cherry JD, English PA, Hennessey K, Giorgi JV, Visscher BR, et al. The relationship between T-cell levels and CMV infection in asymptomatic HIV-1 antibody-positive homosexual men. J Acquir Immune Defic Syndr 1993;6:407-13.
• 39 Douek D. HIV disease progression: Immune activation, microbes, and a leaky gut. Top HIV Med 2007;15:114-7.
• 40 Grivel JC, Ito Y, Fagà G, Santoro F, Shaheen F, Malnati MS, et al. Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6. Nat Med 2001;7:1232-5.
• 41 Cole AM. Innate host defense of human vaginal and cervical mucosae. Curr Top Microbiol Immunol 2006;306:199-230.
• 42 Ganz T. Defensins: Antimicrobial peptides of innate immunity. Nat Rev Immunol 2003;3:710-20.
• 43 Doncel GF, Joseph T, Thurman AR. Role of semen in HIV-1 transmission: Inhibitor or facilitator? Am J Reprod Immunol 2011;65:292-301.
• 44 Murphy PM. Viral exploitation and subversion of the immune system through chemokine mimicry. Nat Immunol 2001;2:116-22.
• 45 Pleskoff O, Tréboute C, Brelot A, Heveker N, Seman M, Alizon M. Identification of a chemokine receptor encoded by human Cytomegalovirus as a cofactor for HIV-1 entry. Science 1997;276:1874-8.
• 46 Margolis DM, Rabson AB, Straus SE, Ostrove JM. Transactivation of the HIV-1 LTR by HSV-1 immediate-early genes. Virology 1992;186:788-91.
• 47 McCarthy M, Auger D, He J, Wood C. Cytomegalovirus and human herpesvirus-6 trans-activate the HIV-1 long terminal repeat via multiple response regions in human fetal astrocytes. J Neurovirol 1998;4:495-511.
• 48 Garzino-Demo A, Chen M, Lusso P, Berneman Z, DiPaolo JA. Enhancement of TAT-induced transactivation of the HIV-1 LTR by two genomic fragments of HHV-6. J Med Virol 1996;50:20-4.
• 49 Caselli E, Galvan M, Santoni F, Rotola A, Caruso A, Cassai E, et al. Human herpesvirus-8 (Kaposi's sarcoma-associated virus) ORF50 increases in vitro cell susceptibility to human immunodeficiency virus type 1 infection. J Gen Virol 2003;84(Pt 5):1123-31.
• 50 Nahmias AJ, Lee FK, Beckman-Nahmias S. Sero-epidemiological and -sociological patterns of herpes simplex virus infection in the world. Scand J Infect Dis Suppl 1990;69:19-36.
• 51 Smith JS, Robinson NJ. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: A global review. J Infect Dis 2002;186 Suppl 1:S3-28.
• 52 Tolfvenstam T, Enbom M, Ghebrekidan H, Rudén U, Linde A, Grandien M, et al. Seroprevalence of viral childhood infections in Eritrea. J Clin Virol 2000;16:49-54.
• 53 Hashido M, Lee FK, Nahmias AJ, Tsugami H, Isomura S, Nagata Y, et al. An epidemiologic study of herpes simplex virus type 1 and 2 infection in Japan based on type-specific serological assays. Epidemiol Infect 1998;120:179-86.
• 54 Shivaswamy KN, Thappa DM, Jaisankar TJ, Sujatha S. High seroprevalence of HSV-1 and HSV-2 in STD clinic attendees and non-high risk controls: A case control study at a referral hospital in south India. Indian J Dermatol Venereol Leprol 2005;71:26-30.
• 55 Looker KJ, Garnett GP, Schmid GP. An estimate of the global prevalence and incidence of herpes simplex virus type 2 infection. Bull World Health Organ 2008;86:805-12, A.
• 56 Agabi YA, Banwat EB, Mawak JD, Lar PM, Dashe N, Dashen MM, et al. Seroprevalence of herpes simplex virus type-2 among patients attending the Sexually Transmitted Infections Clinic in Jos, Nigeria. J Infect Dev Ctries 2010;4:572-5.
• 57 Weiss H. Epidemiology of herpes simplex virus type 2 infection in the developing world. Herpes 2004;11 Suppl 1:24A-35A.
• 58 Xu F, Sternberg MR, Gottlieb S, Berman SM, Markowitz LE, Forhan S, et al. Seroprevalence of herpes simplex virus type 2 among persons aged 14-49 years-United States, 2005-2008. MMWR Morb Mortal Wkly Rep 2010;59:456-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20414188. [Last accessed on 2016 Feb 02].
• 59 Cunningham AL, Taylor R, Taylor J, Marks C, Shaw J, Mindel A. Prevalence of infection with herpes simplex virus types 1 and 2 in Australia: A nationwide population based survey. Sex Transm Infect 2006;82:164-8.
• 60 Lin H, He N, Su M, Feng J, Chen L, Gao M. Herpes simplex virus infections among rural residents in eastern China. BMC Infect Dis 2011;11:69.
• 61 Cowan FM, French RS, Mayaud P, Gopal R, Robinson NJ, de Oliveira SA, et al. Seroepidemiological study of herpes simplex virus types 1 and 2 in Brazil, Estonia, India, Morocco, and Sri Lanka. Sex Transm Infect 2003;79:286-90.
• 62 Schneider JA, Lakshmi V, Dandona R, Kumar GA, Sudha T, Dandona L. Population-based seroprevalence of HSV-2 and syphilis in Andhra Pradesh state of India. BMC Infect Dis 2010;10:59.
• 63 Weiss HA, Buvé A, Robinson NJ, Van Dyck E, Kahindo M, Anagonou S, et al. The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations. AIDS 2001;15 Suppl 4:S97-108.
• 64 Freeman EE, Orroth KK, White RG, Glynn JR, Bakker R, Boily MC, et al. Proportion of new HIV infections attributable to herpes simplex 2 increases over time: Simulations of the changing role of sexually transmitted infections in sub-Saharan African HIV epidemics. Sex Transm Infect 2007;83 Suppl 1:i17-24.
• 65 Bohl DD, Katz KA, Bernstein K, Wong E, Raymond HF, Klausner JD, et al. Prevalence and correlates of herpes simplex virus type-2 infection among men who have sex with men, san francisco, 2008. Sex Transm Dis 2011;38:617-21.
• 66 Jacob S, Gopal T, Kanagasabai S, Durairaj A, Sushi K, Arumugam G. Herpes simplex virus 2 infection in HIV-seropositive individuals in Tamil Nadu, India. Int J Med Sci Public Health 2015;4(3):404-7. Available from: http://www.scopemed.org/?mno=172880. [Last accessed on 2016 Feb 01].
• 67 Lafferty WE, Downey L, Celum C, Wald A. Herpes simplex virus type 1 as a cause of genital herpes: Impact on surveillance and prevention. J Infect Dis 2000;181:1454-7.
• 68 Manavi K, McMillan A, Ogilvie M. Herpes simplex virus type 1 remains the principal cause of initial anogenital herpes in Edinburgh, Scotland. Sex Transm Dis 2004;31:322-4.
• 69 Roberts CM, Pfister JR, Spear SJ. Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students. Sex Transm Dis 2003;30:797-800.
• 70 Dinotta F, De Pasquale R, Nasca MR, Tedeschi A, Micali G. Disseminated herpes simplex infection in a HIV+patient. G Ital Dermatol Venereol 2009;144:205-9.
• 71 Arvin A, Abendroth A. VZV: immunobiology and host response. In: Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, et al, editors. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Ch. 39. Cambridge: Cambridge University Press; 2007. p. 1-31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21348065. [Last accessed on 2016 Feb 02].
• 72 Wharton M. The epidemiology of varicella-zoster virus infections. Infect Dis Clin North Am 1996;10:571-81.
• 73 Lolekha S, Tanthiphabha W, Sornchai P, Kosuwan P, Sutra S, Warachit B, et al. Effect of climatic factors and population density on varicella zoster virus epidemiology within a tropical country. Am J Trop Med Hyg 2001;64:131-6.
• 74 Lokeshwar MR, Agrawal A, Subbarao SD, Chakraborty MS, Ram Prasad AV, Weil J, et al. Age related seroprevalence of antibodies to varicella in India. Indian Pediatr 2000;37:714-9.
• 75 Lee BW. Review of varicella zoster seroepidemiology in India and Southeast Asia. Trop Med Int Health 1998;3:886-90.
• 76 Thomas SL, Hall AJ. What does epidemiology tell us about risk factors for herpes zoster? Lancet Infect Dis 2004;4:26-33.
• 77 Abdul Latheef EN, Pavithran K. Herpes zoster: A clinical study in 205 patients. Indian J Dermatol 2011;56:529-32.
• 78 Liesegang TJ. The varicella-zoster virus: Systemic and ocular features. J Am Acad Dermatol 1984;11(2 Pt 1):165-91.
• 79 Gebo KA, Kalyani R, Moore RD, Polydefkis MJ. The incidence of, risk factors for, and sequelae of herpes zoster among HIV patients in the highly active antiretroviral therapy era. J Acquir Immune Defic Syndr 2005;40:169-74.
• 80 Birlea M, Arendt G, Orhan E, Schmid DS, Bellini WJ, Schmidt C, et al. Subclinical reactivation of varicella zoster virus in all stages of HIV infection. J Neurol Sci 2011;304:22-4.
• 81 Chakraborty N, Bhattacharyya S, De C, Mukherjee A, Bhattacharya D, Santra S, et al. Incidence of multiple Herpesvirus infection in HIV seropositive patients, a big concern for Eastern Indian scenario. Virol J 2010;7:147.
• 82 Goldberg DE, Smithen LM, Angelilli A, Freeman WR. HIV-associated retinopathy in the HAART era. Retina 2005;25:633-49.
• 83 Gershon AA. Prevention and treatment of VZV infections in patients with HIV. Herpes 2001;8:32-6.
• 84 McGeoch DJ, Cook S, Dolan A, Jamieson FE, Telford EA. Molecular phylogeny and evolutionary timescale for the family of mammalian herpesviruses. J Mol Biol 1995;247:443-58.
• 85 Balfour HH Jr., Sifakis F, Sliman JA, Knight JA, Schmeling DO, Thomas W. Age-specific prevalence of Epstein-Barr virus infection among individuals aged 6-19 years in the United States and factors affecting its acquisition. J Infect Dis 2013;208:1286-93.
• 86 Svahn A, Berggren J, Parke A, Storsaeter J, Thorstensson R, Linde A. Changes in seroprevalence to four herpesviruses over 30 years in Swedish children aged 9-12 years. J Clin Virol 2006;37:118-23.
• 87 Chen CY, Huang KY, Shen JH, Tsao KC, Huang YC. A large-scale seroprevalence of Epstein-Barr virus in Taiwan. PLoS One 2015;10:e0115836.
• 88 Mekmullica J, Kritsaneepaiboon S, Pancharoen C. Risk factors for Epstein-Barr virus infection in Thai infants. Southeast Asian J Trop Med Public Health 2003;34:395-7.
• 89 Schaftenaar E, Verjans GM, Getu S, McIntyre JA, Struthers HE, Osterhaus AD, et al. High seroprevalence of human herpesviruses in HIV-infected individuals attending primary healthcare facilities in rural South Africa. PLoS One 2014;9:e99243.
• 90 Luchsinger V, Luzoro A, Martínez MJ. High seroprevalence of Cytomegalovirus, herpes simplex type 1 virus and Epstein Barr virus infection among human immunodeficiency virus-infected adults. Rev Med Chil 2010;138:809-14.
• 91 He N, Chen L, Lin HJ, Zhang M, Wei J, Yang JH, et al. Multiple viral coinfections among HIV/AIDS patients in China. Biosci Trends 2011;5:1-9.
• 92 McClain KL. Epstein-Barr virus and HIV-AIDS-associated diseases. Biomed Pharmacother 2001;55:348-52.
• 93 Dhir AA, Sawant SP. Malignancies in HIV: The Indian scenario. Curr Opin Oncol 2008;20:517-21.
• 94 Saple DG, Shah I, Surjushe AU, Murthy A, Chudgar P, Gote PD. Lymphoma in HIV patients: Varied presentations. Indian J Med Paediatr Oncol 2010;31:39-42.
• 95 Cannon MJ. Congenital Cytomegalovirus (CMV) epidemiology and awareness. J Clin Virol 2009;46 Suppl 4:S6-10.
• 96 Staras SA, Dollard SC, Radford KW, Flanders WD, Pass RF, Cannon MJ. Seroprevalence of Cytomegalovirus infection in the United States, 1988-1994. Clin Infect Dis 2006;43:1143-51.
• 97 Seale H, MacIntyre CR, Gidding HF, Backhouse JL, Dwyer DE, Gilbert L. National serosurvey of Cytomegalovirus in Australia. Clin Vaccine Immunol 2006;13:1181-4.
• 98 Cannon MJ, Schmid DS, Hyde TB. Review of Cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol 2010;20:202-13.
• 99 Kothari A, Ramachandran VG, Gupta P, Singh B, Talwar V. Seroprevalence of Cytomegalovirus among voluntary blood donors in Delhi, India. J Health Popul Nutr 2002;20:348-51.
• 100 Rabenau HF, Lennemann T, Kircher C, Gürtler L, Staszewski S, Preiser W, et al. Prevalence- and gender-specific immune response to opportunistic infections in HIV-infected patients in Lesotho. Sex Transm Dis 2010;37:454-9.
• 101 Kryger P, Gerstoft J, Pedersen NS, Nielsen JO. Increased prevalence of Cytomegalovirus antibodies in homosexual men with syphilis: Relation to sexual behaviour. Scand J Infect Dis 1984;16:381-4.
• 102 Drew WL, Sweet ES, Miner RC, Mocarski ES Multiple infections by Cytomegalovirus in patients with acquired immunodeficiency syndrome: Documentation by Southern blot hybridization. J Infect Dis 1984;150:952-3.
• 103 Ford N, Shubber Z, Saranchuk P, Pathai S, Durier N, O'Brien DP, et al. Burden of HIV-related Cytomegalovirus retinitis in resource-limited settings: A systematic review. Clin Infect Dis 2013;57:1351-61.
• 104 Griffiths PD. CMV as a cofactor enhancing progression of AIDS. J Clin Virol 2006;35:489-92.
• 105 Chiu HM, Wu MS, Hung CC, Shun CT, Lin JT. Low prevalence of Helicobacter pylori but high prevalence of Cytomegalovirus-associated peptic ulcer disease in AIDS patients: Comparative study of symptomatic subjects evaluated by endoscopy and CD4 counts. J Gastroenterol Hepatol 2004;19:423-8.
• 106 Fowotade A, Okonko IO, Agbede OO, Suleiman ST. High seropositivity of IgG and IgM antibodies against Cytomegalovirus (CMV) among HIV-1 seropositive patients in Ilorin, Nigeria. Afr Health Sci 2015;15:1-9.
• 107 Silva CA, Oliveira AC, Vilas-Boas L, Fink MC, Pannuti CS, Vidal JE. Neurologic Cytomegalovirus complications in patients with AIDS: Retrospective review of 13 cases and review of the literature. Rev Inst Med Trop Sao Paulo 2010;52:305-10.
• 108 Salahuddin SZ, Ablashi DV, Markham PD, Josephs SF, Sturzenegger S, Kaplan M, et al. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 1986;234:596-601.
• 109 De Bolle L, Naesens L, De Clercq E. Update on human herpesvirus 6 biology, clinical features, and therapy. Clin Microbiol Rev 2005;18:217-45.
• 110 Chua KB, Khairullah NS, Hooi PS. Seroepidemiology of human herpesvirus 6 in a population seen in the University Hospital, Kuala Lumpur, Malaysia. Southeast Asian J Trop Med Public Health 1996;27:91-5.
• 111 Wu Z, Mu G, Wang L. Seroprevalence of human herpesvirus-6 in healthy population in two provinces of north China. Chin Med Sci J 1997;12:111-4.
• 112 Ranger S, Patillaud S, Denis F, Himmich A, Sangare A, M'Boup S, et al. Seroepidemiology of human herpesvirus-6 in pregnant women from different parts of the world. J Med Virol 1991;34:194-8.
• 113 Braun DK, Dominguez G, Pellett PE. Human herpesvirus 6. Clin Microbiol Rev 1997;10:521-67.
• 114 Ablashi DV, Berneman ZN, Kramarsky B, Whitman J Jr, Asano Y, Pearson GR. Human herpesvirus-7 (HHV-7): current status. Clin Diagn Virol. 1995;4(1):1-13.
• 115 Inoue N, Dambaugh TR, Pellett PE. Molecular biology of human herpesviruses 6A and 6B. Infect Agents Dis 1993;2:343-60.
• 116 Bates M, Monze M, Bima H, Kapambwe M, Clark D, Kasolo FC, et al. Predominant human herpesvirus 6 variant A infant infections in an HIV-1 endemic region of Sub-Saharan Africa. J Med Virol 2009;81:779-89.
• 117 Lusso P, Gallo RC. Human herpesvirus 6 in AIDS. Immunol Today 1995;16:67-71.
• 118 Lusso P, Crowley RW, Malnati MS, Di Serio C, Ponzoni M, Biancotto A, et al. Human herpesvirus 6A accelerates AIDS progression in macaques. Proc Natl Acad Sci U S A 2007;104:5067-72.
• 119 Frenkel N, Schirmer EC, Wyatt LS, Katsafanas G, Roffman E, Danovich RM, et al. Isolation of a new herpesvirus from human CD4+T cells. Proc Natl Acad Sci U S A 1990;87:748-52.
• 120 Berneman ZN, Ablashi DV, Li G, Eger-Fletcher M, Reitz MS Jr., Hung CL, et al. Human herpesvirus 7 is a T-lymphotropic virus and is related to, but significantly different from, human herpesvirus 6 and human Cytomegalovirus. Proc Natl Acad Sci U S A 1992;89:10552-6.
• 121 Black JB, Pellett PE. Human herpesvirus 7. Rev Med Virol 1999;9:245-62.
• 122 Wyatt LS, Rodriguez WJ, Balachandran N, Frenkel N. Human herpesvirus 7: Antigenic properties and prevalence in children and adults. J Virol 1991;65:6260-5.
• 123 Krueger GR, Koch B, Leyssens N, Berneman Z, Rojo J, Horwitz C, et al. Comparison of seroprevalences of human herpesvirus-6 and -7 in healthy blood donors from nine countries. Vox Sang 1998;75:193-7.
• 124 Kositanont U, Wasi C, Ekpatcha N, Poomchart A, Likanonsakul S, Suphanip I, et al. Seroprevalence of human herpesvirus 6 and 7 infections in the Thai population. Asian Pac J Allergy Immunol 1995;13:151-7.
• 125 Yoshikawa T, Asano Y, Kobayashi I, Nakashima T, Yazaki T, Suga S, et al. Seroepidemiology of human herpesvirus 7 in healthy children and adults in Japan. J Med Virol 1993;41:319-23.
• 126 Reeves WC, Stamey FR, Black JB, Mawle AC, Stewart JA, Pellett PE. Human herpesviruses 6 and 7 in chronic fatigue syndrome: A case-control study. Clin Infect Dis 2000;31:48-52.
• 127 Schwartz KL, Richardson SE, Ward KN, Donaldson C, MacGregor D, Banwell B, et al. Delayed primary HHV-7 infection and neurologic disease. Pediatrics 2014;133:e1541-7.
• 128 Epstein LG, Shinnar S, Hesdorffer DC, Nordli DR, Hamidullah A, Benn EK, et al. Human herpesvirus 6 and 7 in febrile status epilepticus: The FEBSTAT study. Epilepsia 2012;53:1481-8.
• 129 Stewart MW. Herpetic (non-Cytomegalovirus) retinal infections in patients with the acquired immunodeficiency syndrome. Curr HIV Res 2013;11:210-9.
• 130 Kosuge H. HHV-6, 7 and their related diseases. J Dermatol Sci 2000;22:205-12.
• 131 Carbone A, Gloghini A. HHV-8-associated lymphoma: State-of-the-art review. Acta Haematol 2007;117:129-31.
• 132 Rohner E, Wyss N, Trelle S, Mbulaiteye SM, Egger M, Novak U, et al. HHV-8 seroprevalence: A global view. Syst Rev 2014;3:11.
• 133 Batista MD, Ferreira S, Sauer MM, Tomiyama H, Giret MT, Pannuti CS, et al. High human herpesvirus 8 (HHV-8) prevalence, clinical correlates and high incidence among recently HIV-1-infected subjects in Sao Paulo, Brazil. PLoS One 2009;4:e5613.
• 134 Mosam A, Aboobaker J, Shaik F. Kaposi's sarcoma in sub-Saharan Africa: A current perspective. Curr Opin Infect Dis 2010;23:119-23.
• 135 Munawwar A, Sharma SK, Gupta S, Singh S. Seroprevalence and determinants of Kaposi sarcoma-associated human herpesvirus 8 in Indian HIV-infected males. AIDS Res Hum Retroviruses 2014;30:1192-6.
• 136 Hunt PW, Martin JN, Sinclair E, Epling L, Teague J, Jacobson MA, et al. Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+T cell recovery on antiretroviral therapy. J Infect Dis 2011;203:1474-83.
• 137 Ioannidis JP, Collier AC, Cooper DA, Corey L, Fiddian AP, Gazzard BG, 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;178:349-59.
• 138 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;25:1265-9.
• 139 Vickerman P, Devine A, Foss AM, Delany-Moretlwe S, Mayaud P, Meyer-Rath G. The cost-effectiveness of herpes simplex virus-2 suppressive therapy with daily aciclovir for delaying HIV disease progression among HIV-1-infected women in South Africa. Sex Transm Dis 2011;38:401-9.
• 140 Lingappa JR, Baeten JM, Wald A, Hughes JP, Thomas KK, Mujugira A, et al. Daily acyclovir 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;375:824-33.
• 141 Vanpouille C, Lisco A, Margolis L. Acyclovir: A new use for an old drug. Curr Opin Infect Dis 2009;22:583-7.
• 142 McMahon MA, Shen L, Siliciano RF. New approaches for quantitating the inhibition of HIV-1 replication by antiviral drugs in vitro and in vivo. Curr Opin Infect Dis 2009;22:574-82.
• 143 Weiss HA, Paz Bailey G, Phiri S, Gresenguet G, LeGoff J, Pepin J, et al. Episodic therapy for genital herpes in sub-saharan Africa: A pooled analysis from three randomized controlled trials. PLoS One 2011;6:e22601.
• 144 Vanpouille C, Lisco A, Grivel JC, Bassit LC, Kauffman RC, Sanchez J, et al. Valacyclovir decreases plasma HIV-1 RNA in HSV-2 seronegative individuals: A randomized placebo-controlled crossover trial. Clin Infect Dis 2015;60:1708-14.
• 145 Barnabas RV, Baeten JM, Lingappa JR, Thomas KK, Hughes JP, Mugo NR, et al. Acyclovir prophylaxis reduces the incidence of herpes zoster among HIV-infected individuals: Results of a randomized clinical trial. J Infect Dis 2015;213:551-5.
• 146 Redd AD, Newell K, Patel EU, Nalugoda F, Ssebbowa P, Kalibbala S, et al. Decreased monocyte activation with daily acyclovir use in HIV-1/HSV-2 coinfected women. Sex Transm Infect 2015;91:485-8.
• 147 Roxby AC, Atkinson C, Asbjörnsdóttir K, Farquhar C, Kiarie JN, Drake AL, et al. Maternal valacyclovir and infant Cytomegalovirus acquisition: A randomized controlled trial among HIV-infected women. PLoS One 2014;9:e87855.
• 148 Yi TJ, Walmsley S, Szadkowski L, Raboud J, Rajwans N, Shannon B, et al. 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;57:1331-8.
• 149 Mujugira A, Magaret AS, Celum C, Baeten JM, Lingappa JR, Morrow RA, et al. Daily acyclovir to decrease herpes simplex virus type 2 (HSV-2) transmission from HSV-2/HIV-1 coinfected persons: A randomized controlled trial. J Infect Dis 2013;208:1366-74.
• 150 Perti T, Saracino M, Baeten JM, Johnston C, Diem K, Ocbamichael N, et al. High-dose valacyclovir decreases plasma HIV-1 RNA more than standard-dose acyclovir in persons coinfected with HIV-1 and HSV-2: A randomized crossover trial. J Acquir Immune Defic Syndr 2013;63:201-8.
• 151 Roxby AC, Drake AL, Ongecha-Owuor F, Kiarie JN, Richardson B, Matemo DN, et al. Effects of valacyclovir on markers of disease progression in postpartum women co-infected with HIV-1 and herpes simplex virus-2. PLoS One 2012;7:e38622.
• 152 Reynolds SJ, Makumbi F, Newell K, Kiwanuka N, Ssebbowa P, Mondo G, 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;12:441-8.