Current HIV/AIDS Reports

, Volume 9, Issue 2, pp 101–110 | Cite as

Should We Treat Acute HIV Infection?

Antiretroviral Therapies (A Pozniak, Section Editor)

Abstract

Critical advances in the early diagnosis of HIV now allow for treatment opportunities during acute infection. It remains unclear whether treatment of acute HIV infection with antiretroviral therapy improves long-term clinical outcomes for the individual and current guidelines are not definitive in recommending therapy at this stage of infection. However, treatment of acute HIV infection may have short-term benefit on viral set point when compared to delayed therapy as well as reducing the risk of transmission to others. Herein we review the immunological and clinical literature to discuss whether we should treat acute HIV infection, both from the perspective of the individual HIV-infected patient and from the public health perspective. As transmission of drug-resistant HIV variants are of concern, we also review recent clinical trial data to provide recommendations for which specific antiretroviral treatment regimens should be considered for the treatment of acute HIV infection.

Keywords

HIV Antiretroviral therapy Clinical trials Observational studies Viral load set point Viral reservoir Drug-resistant HIV transmission 

Notes

Disclosure

No potential conflicts of interest relevant to this article were reported.

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    •• Cohen MS, Shaw GM, McMichael AJ, Haynes BF. Acute HIV-1 Infection. N Engl J Med. 2011;364(20):1943–54. This recent review gives an excellent up-to-date summary of the basic science of HIV transmission events along with important vaccine considerations. PubMedCrossRefGoogle Scholar
  2. 2.
    Stacey AR, Norris PJ, Qin L, Haygreen EA, Taylor E, Heitman J, et al. Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. J Virol. 2009;83(8):3719–33.PubMedCrossRefGoogle Scholar
  3. 3.
    Tincati C, Biasin M, Bandera A, Violin M, Marchetti G, Piacentini L, et al. Early initiation of highly active antiretroviral therapy fails to reverse immunovirological abnormalities in gut-associated lymphoid tissue induced by acute HIV infection. Antivir Ther. 2009;14(3):321–30.PubMedGoogle Scholar
  4. 4.
    Mehandru S, Poles MA, Tenner-Racz K, Jean-Pierre P, Manuelli V, Lopez P, et al. Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection. PLoS Med. 2006;3(12):e484.PubMedCrossRefGoogle Scholar
  5. 5.
    Panel on Antiretroviral Guidelines for Adults and Adolescents: Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. January 10, 2011. http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.
  6. 6.
    Thompson MA, Aberg JA, Cahn P, Montaner JS, Rizzardini G, Telenti A, et al. Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel. JAMA. 2010;304(3):321–33.PubMedCrossRefGoogle Scholar
  7. 7.
    Wawer MJ, Gray RH, Sewankambo NK, Serwadda D, Li X, Laeyendecker O, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis. 2005;191(9):1403–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Ma ZM, Stone M, Piatak Jr M, Schweighardt B, Haigwood NL, Montefiori D, et al. High specific infectivity of plasma virus from the pre-ramp-up and ramp-up stages of acute simian immunodeficiency virus infection. J Virol. 2009;83(7):3288–97.PubMedCrossRefGoogle Scholar
  9. 9.
    Bollinger RC, Brookmeyer RS, Mehendale SM, Paranjape RS, Shepherd ME, Gadkari DA, et al. Risk factors and clinical presentation of acute primary HIV infection in India. JAMA. 1997;278(23):2085–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, et al. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science. 1997;278(5342):1447–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection. N Engl J Med. 1998;339(1):33–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Schacker T, Collier AC, Hughes J, Shea T, Corey L. Clinical and epidemiologic features of primary HIV infection. Ann Intern Med. 1996;125(4):257–64.PubMedGoogle Scholar
  13. 13.
    Ho DD, Rota TR, Schooley RT, Kaplan JC, Allan JD, Groopman JE, et al. Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med. 1985;313(24):1493–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Niu MT, Stein DS, Schnittman SM. Primary human immunodeficiency virus type 1 infection: review of pathogenesis and early treatment intervention in humans and animal retrovirus infections. J Infect Dis. 1993;168(6):1490–501.PubMedCrossRefGoogle Scholar
  15. 15.
    Quinn TC. Acute primary HIV infection. JAMA. 1997;278(1):58–62.PubMedCrossRefGoogle Scholar
  16. 16.
    Dorrucci M, Rezza G, Vlahov D, Pezzotti P, Sinicco A, Nicolosi A, et al. Clinical characteristics and prognostic value of acute retroviral syndrome among injecting drug users. Italian Seroconversion Study. AIDS. 1995;9(6):597–604.PubMedCrossRefGoogle Scholar
  17. 17.
    Henrard DR, Phillips JF, Muenz LR, Blattner WA, Wiesner D, Eyster ME, et al. Natural history of HIV-1 cell-free viremia. JAMA. 1995;274(7):554–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A. 2008;105(21):7552–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Lee HY, Giorgi EE, Keele BF, Gaschen B, Athreya GS, Salazar-Gonzalez JF, et al. Modeling sequence evolution in acute HIV-1 infection. J Theor Biol. 2009;261(2):341–60.PubMedCrossRefGoogle Scholar
  20. 20.
    Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, Polis M, et al. New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol. 2003;41(10):4531–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Damond F, Avettand-Fenoel V, Collin G, Roquebert B, Plantier JC, Ganon A, et al. Evaluation of an upgraded version of the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test for HIV-1 load quantification. J Clin Microbiol. 2010;48(4):1413–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Daar ES, Little S, Pitt J, Santangelo J, Ho P, Harawa N, et al. Diagnosis of primary HIV-1 infection. Los Angeles County Primary HIV Infection Recruitment Network. Ann Intern Med. 2001;134(1):25–9.PubMedGoogle Scholar
  23. 23.
    Rich JD, Merriman NA, Mylonakis E, Greenough TC, Flanigan TP, Mady BJ, et al. Misdiagnosis of HIV infection by HIV-1 plasma viral load testing: a case series. Ann Intern Med. 1999;130(1):37–9.PubMedGoogle Scholar
  24. 24.
    Little SJ, McLean AR, Spina CA, Richman DD, Havlir DV. Viral dynamics of acute HIV-1 infection. J Exp Med. 1999;190(6):841–50.PubMedCrossRefGoogle Scholar
  25. 25.
    Fiebig EW, Wright DJ, Rawal BD, Garrett PE, Schumacher RT, Peddada L, et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS. 2003;17(13):1871–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Saville RD, Constantine NT, Cleghorn FR, Jack N, Bartholomew C, Edwards J, et al. Fourth-generation enzyme-linked immunosorbent assay for the simultaneous detection of human immunodeficiency virus antigen and antibody. J Clin Microbiol. 2001;39(7):2518–24.PubMedCrossRefGoogle Scholar
  27. 27.
    Sickinger E, Jonas G, Yem AW, Goller A, Stieler M, Brennan C, et al. Performance evaluation of the new fully automated human immunodeficiency virus antigen-antibody combination assay designed for blood screening. Transfusion. 2008;48(4):584–93.PubMedCrossRefGoogle Scholar
  28. 28.
    Branson BM. State of the art for diagnosis of HIV infection. Clin Infect Dis. 2007;45 Suppl 4:S221–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Eshleman SH, Khaki L, Laeyendecker O, Piwowar-Manning E, Johnson-Lewis L, Husnik M, et al. Detection of individuals with acute HIV-1 infection using the ARCHITECT HIV Ag/Ab Combo assay. J Acquir Immune Defic Syndr. 2009;52(1):121–4.PubMedCrossRefGoogle Scholar
  30. 30.
    Daar ES, Pilcher CD, Hecht FM. Clinical presentation and diagnosis of primary HIV-1 infection. Curr Opin HIV AIDS. 2008;3(1):10–5.PubMedCrossRefGoogle Scholar
  31. 31.
    Rieder P, Joos B, von Wyl V, Kuster H, Grube C, Leemann C, et al. HIV-1 transmission after cessation of early antiretroviral therapy among men having sex with men. AIDS. 2010;24(8):1177–83.PubMedCrossRefGoogle Scholar
  32. 32.
    Markowitz M, Vaida F, Hare CB, Boden D, Mohri H, Hecht FM, et al. The virologic and immunologic effects of cyclosporine as an adjunct to antiretroviral therapy in patients treated during acute and early HIV-1 infection. J Infect Dis. 2010;201(9):1298–302.PubMedCrossRefGoogle Scholar
  33. 33.
    Attia S, Egger M, Muller M, Zwahlen M, Low N. Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis. AIDS. 2009;23(11):1397–404.PubMedCrossRefGoogle Scholar
  34. 34.
    Kinloch-De Loes S, Hirschel BJ, Hoen B, Cooper DA, Tindall B, Carr A, et al. A controlled trial of zidovudine in primary human immunodeficiency virus infection. N Engl J Med. 1995;333(7):408–13.PubMedCrossRefGoogle Scholar
  35. 35.
    Niu MT, Bethel J, Holodniy M, Standiford HC, Schnittman SM. Zidovudine treatment in patients with primary (acute) human immunodeficiency virus type 1 infection: a randomized, double-blind, placebo-controlled trial. DATRI 002 Study Group. Division of AIDS Treatment Research Initiative. J Infect Dis. 1998;178(1):80–91.PubMedCrossRefGoogle Scholar
  36. 36.
    •• Hogan CM, Degruttola V, Sun X, Fiscus SA, Del Rio C, Hare CB et al. The Setpoint Study (ACTG A5217): Effect of Immediate Versus Deferred Antiretroviral Therapy on Virologic Set Point in Recently HIV-1-Infected Individuals. J Infect Dis. 2011;205(1):87–96. This important randomized controlled study compared early versus delayed ART in early (< 6 months) HIV infection. Although this study was powered to determine whether viral load setpoint could be altered after treatment interruption, the study was stopped early (and the viral load setpoint outcome could not be evaluated) because subjects who were not treated within 6 months of acute HIV diagnosis experienced more rapid disease progression. PubMedCrossRefGoogle Scholar
  37. 37.
    Grijsen M, Steingrover R, Wit F, de Wolf F, Lange J, Verbon A, Brinkman K, van der Ende M, Schuitemaker H, Prins J. An RCT Comparing No Treatment with 24 or 60 Weeks of Temporary ART during Primary HIV Infection. Conference on Retroviruses and Opportunistic Infections(CROI) 2011.Google Scholar
  38. 38.
    Fidler S, Spartac Trial Investigators. The effect of short-course antiretroviral therapy in primary HIV infection: final results from an international randomised controlled trial; SPARTAC. 6th International AIDS Society conference on HIV pathogenesis, treatment and prevention 2011.Google Scholar
  39. 39.
    Streeck H, Jessen H, Alter G, Teigen N, Waring MT, Jessen A, et al. Immunological and virological impact of highly active antiretroviral therapy initiated during acute HIV-1 infection. J Infect Dis. 2006;194(6):734–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Hecht FM, Wang L, Collier A, Little S, Markowitz M, Margolick J, et al. A multicenter observational study of the potential benefits of initiating combination antiretroviral therapy during acute HIV infection. J Infect Dis. 2006;194(6):725–33.PubMedCrossRefGoogle Scholar
  41. 41.
    Fidler S, Fox J, Touloumi G, Pantazis N, Porter K, Babiker A, et al. Slower CD4 cell decline following cessation of a 3 month course of HAART in primary HIV infection: findings from an observational cohort. AIDS. 2007;21(10):1283–91.PubMedCrossRefGoogle Scholar
  42. 42.
    von Wyl V, Gianella S, Fischer M, Niederoest B, Kuster H, Battegay M, et al. Early antiretroviral therapy during primary HIV-1 infection results in a transient reduction of the viral setpoint upon treatment interruption. PLoS One. 2011;6(11):e27463.PubMedCrossRefGoogle Scholar
  43. 43.
    Hoen B, Cooper DA, Lampe FC, Perrin L, Clumeck N, Phillips AN, et al. Predictors of virological outcome and safety in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy: QUEST GW PROB3005. Clin Infect Dis. 2007;45(3):381–90.PubMedCrossRefGoogle Scholar
  44. 44.
    Tilling R, Kinloch S, Goh LE, Cooper D, Perrin L, Lampe F, et al. Parallel decline of CD8+/CD38++ T cells and viraemia in response to quadruple highly active antiretroviral therapy in primary HIV infection. AIDS. 2002;16(4):589–96.PubMedCrossRefGoogle Scholar
  45. 45.
    Jain V, Hartogensis W, Bacchetti P, Hunt P, Epling L, Sinclair E, Lee T-H, Busch M, Hecht F, Deeks S. ART Initiation during Acute/Early HIV Infection Compared to Later ART Initiation Is Associated with Improved Immunologic and Virologic Parameters during Suppressive ART, Paper # 517. Conference on Retroviruses and Opportunistic Infections (CROI) 2011.Google Scholar
  46. 46.
    Ananworanich J, Schuetz A, Sereti I, Rerknimitr R, deSouza M, Dewar R, Chomont N, Phanuphak N, Phanuphak P, Kim J, and RV254/SEARCH 010 Study Group. Mega-HAART Suppresses HIV Viremia, Reduces Viral Reservoir, and Restores Immunity in Peripheral Blood and Sigmoid Colon of Acute HIV-infected Subjects, Paper # 516. Conference on Retroviruses and Opportunistic Infections (CROI) 2011.Google Scholar
  47. 47.
    Buzon MJ SK, Stone AB, Pereyra P, Rosenberg E, Yu XG, Lichterfeld M. Reduced HIV-1 reservoir size after 10 years of suppressive antiretroviral therapy in patients initiating treatment during primary infection, Abstract 33. The Fifth International Workshop on HIV Persistence During Therapy 2011.Google Scholar
  48. 48.
    Oxenius A, Price DA, Easterbrook PJ, O'Callaghan CA, Kelleher AD, Whelan JA, et al. Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes. Proc Natl Acad Sci U S A. 2000;97(7):3382–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Rosenberg ES, Altfeld M, Poon SH, Phillips MN, Wilkes BM, Eldridge RL, et al. Immune control of HIV-1 after early treatment of acute infection. Nature. 2000;407(6803):523–6. doi:10.1038/35035103.PubMedCrossRefGoogle Scholar
  50. 50.
    Lu W, Arraes LC, Ferreira WT, Andrieu JM. Therapeutic dendritic-cell vaccine for chronic HIV-1 infection. Nat Med. 2004;10(12):1359–65.PubMedCrossRefGoogle Scholar
  51. 51.
    Ide F, Nakamura T, Tomizawa M, Kawana-Tachikawa A, Odawara T, Hosoya N, et al. Peptide-loaded dendritic-cell vaccination followed by treatment interruption for chronic HIV-1 infection: a phase 1 trial. J Med Virol. 2006;78(6):711–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Rinaldo CR. Dendritic cell-based human immunodeficiency virus vaccine. J Intern Med. 2009;265(1):138–58.PubMedCrossRefGoogle Scholar
  53. 53.
    Dorrell L, Williams P, Suttill A, Brown D, Roberts J, Conlon C, et al. Safety and tolerability of recombinant modified vaccinia virus Ankara expressing an HIV-1 gag/multiepitope immunogen (MVA.HIVA) in HIV-1-infected persons receiving combination antiretroviral therapy. Vaccine. 2007;25(17):3277–83.PubMedCrossRefGoogle Scholar
  54. 54.
    Gandhi RT, O'Neill D, Bosch RJ, Chan ES, Bucy RP, Shopis J, et al. A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic cells vs. canarypox-HIV alone in HIV-1-infected patients on antiretroviral therapy. Vaccine. 2009;27(43):6088–94.PubMedCrossRefGoogle Scholar
  55. 55.
    Aline F, Brand D, Pierre J, Roingeard P, Severine M, Verrier B, et al. Dendritic cells loaded with HIV-1 p24 proteins adsorbed on surfactant-free anionic PLA nanoparticles induce enhanced cellular immune responses against HIV-1 after vaccination. Vaccine. 2009;27(38):5284–91.PubMedCrossRefGoogle Scholar
  56. 56.
    Lori F, Calarota SA, Lisziewicz J. Nanochemistry-based immunotherapy for HIV-1. Curr Med Chem. 2007;14(18):1911–9.PubMedCrossRefGoogle Scholar
  57. 57.
    El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, Arduino RC, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355(22):2283–96.PubMedCrossRefGoogle Scholar
  58. 58.
    Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med. 2009;360(18):1815–26.PubMedCrossRefGoogle Scholar
  59. 59.
    Lodi S, Phillips A, Touloumi G, Geskus R, Meyer L, Thiebaut R, et al. Time from human immunodeficiency virus seroconversion to reaching CD4+ cell count thresholds <200, <350, and <500 Cells/mm(3): assessment of need following changes in treatment guidelines. Clin Infect Dis. 2011;53(8):817–25.PubMedCrossRefGoogle Scholar
  60. 60.
    •• Writing Committee for the CASCADE Collaboration. Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters. Arch Intern Med. 2011;171(17):1560–9. This important study found that CD4+ T-cell counts less than 500 but not 500–799 cells/mm 3 were associated with slower disease progression and increased mortality, which strongly supports initiation of ART in HIV-infected persons with less than 500 and the rapidity with which newly infected subjects meet current treatment guidelines. CrossRefGoogle Scholar
  61. 61.
    Huang X, Sara L, Fox Z, Phillips A, Johnson A, Porter K, Xu X, Wu H and the Beijing PRIMO Cohort and CASCADE Seroconverter Cohorts Study Groups. Patterns of decrease in CD4 cell count after seroconversion: comparison between Beijing PRIMO cohort and CASCADE seroconverter cohorts. 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention 2011.Google Scholar
  62. 62.
    Friis-Moller N, Reiss P, Sabin CA, Weber R, Monforte A, El-Sadr W, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007;356(17):1723–35.PubMedCrossRefGoogle Scholar
  63. 63.
    Worm SW, Sabin C, Weber R, Reiss P, El-Sadr W, Dabis F, et al. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study. J Infect Dis. 2009;201(3):318–30.CrossRefGoogle Scholar
  64. 64.
    Uy J, Armon C, Buchacz K, Wood K, Brooks JT. Initiation of HAART at higher CD4 cell counts is associated with a lower frequency of antiretroviral drug resistance mutations at virologic failure. J Acquir Immune Defic Syndr. 2009;51(4):450–3.PubMedCrossRefGoogle Scholar
  65. 65.
    Freedberg KA, Losina E, Weinstein MC, Paltiel AD, Cohen CJ, Seage GR, et al. The cost effectiveness of combination antiretroviral therapy for HIV disease. N Engl J Med. 2001;344(11):824–31.PubMedCrossRefGoogle Scholar
  66. 66.
    Schackman BR, Goldie SJ, Weinstein MC, Losina E, Zhang H, Freedberg KA. Cost-effectiveness of earlier initiation of antiretroviral therapy for uninsured HIV-infected adults. Am J Public Health. 2001;91(9):1456–63.PubMedCrossRefGoogle Scholar
  67. 67.
    Mauskopf J, Kitahata M, Kauf T, Richter A, Tolson J. HIV antiretroviral treatment: early versus later. J Acquir Immune Defic Syndr. 2005;39(5):562–9.PubMedGoogle Scholar
  68. 68.
    Chen RY, Accortt NA, Westfall AO, Mugavero MJ, Raper JL, Cloud GA, et al. Distribution of health care expenditures for HIV-infected patients. Clin Infect Dis. 2006;42(7):1003–10.PubMedCrossRefGoogle Scholar
  69. 69.
    Quinn TC, Brookmeyer R, Kline R, Shepherd M, Paranjape R, Mehendale S, et al. Feasibility of pooling sera for HIV-1 viral RNA to diagnose acute primary HIV-1 infection and estimate HIV incidence. AIDS. 2000;14(17):2751–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Powers KA, Poole C, Pettifor AE, Cohen MS. Rethinking the heterosexual infectivity of HIV-1: a systematic review and meta-analysis. Lancet Infect Dis. 2008;8(9):553–63.PubMedCrossRefGoogle Scholar
  71. 71.
    Pilcher CD, Tien HC, Eron Jr JJ, Vernazza PL, Leu SY, Stewart PW, et al. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis. 2004;189(10):1785–92.PubMedCrossRefGoogle Scholar
  72. 72.
    Hollingsworth TD, Anderson RM, Fraser C. HIV-1 transmission, by stage of infection. J Infect Dis. 2008;198(5):687–93.PubMedCrossRefGoogle Scholar
  73. 73.
    Brenner BG, Roger M, Routy JP, Moisi D, Ntemgwa M, Matte C, et al. High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis. 2007;195(7):951–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Pao D, Fisher M, Hue S, Dean G, Murphy G, Cane PA, et al. Transmission of HIV-1 during primary infection: relationship to sexual risk and sexually transmitted infections. AIDS. 2005;19(1):85–90.PubMedCrossRefGoogle Scholar
  75. 75.
    Yerly S, Vora S, Rizzardi P, Chave JP, Vernazza PL, Flepp M, et al. Acute HIV infection: impact on the spread of HIV and transmission of drug resistance. AIDS. 2001;15(17):2287–92.PubMedCrossRefGoogle Scholar
  76. 76.
    Jacquez JA, Koopman JS, Simon CP, Longini Jr IM. Role of the primary infection in epidemics of HIV infection in gay cohorts. J Acquir Immune Defic Syndr. 1994;7(11):1169–84.PubMedGoogle Scholar
  77. 77.
    Kretzschmar M, Dietz K. The effect of pair formation and variable infectivity on the spread of an infection without recovery. Math Biosci. 1998;148(1):83–113.PubMedCrossRefGoogle Scholar
  78. 78.
    Abu-Raddad LJ, Longini Jr IM. No HIV stage is dominant in driving the HIV epidemic in sub-Saharan Africa. AIDS. 2008;22(9):1055–61.PubMedCrossRefGoogle Scholar
  79. 79.
    Koopman JS, Jacquez JA, Welch GW, Simon CP, Foxman B, Pollock SM, et al. The role of early HIV infection in the spread of HIV through populations. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;14(3):249–58.PubMedCrossRefGoogle Scholar
  80. 80.
    Xiridou M, Geskus R, de Wit J, Coutinho R, Kretzschmar M. Primary HIV infection as source of HIV transmission within steady and casual partnerships among homosexual men. AIDS. 2004;18(9):1311–20.PubMedCrossRefGoogle Scholar
  81. 81.
    Pinkerton SD. How many sexually-acquired HIV infections in the USA are due to acute-phase HIV transmission? AIDS. 2007;21(12):1625–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Prabhu VS, Hutchinson AB, Farnham PG, Sansom SL. Sexually acquired HIV infections in the United States due to acute-phase HIV transmission: an update. AIDS. 2009;23(13):1792–4.PubMedCrossRefGoogle Scholar
  83. 83.
    Granich RM, Gilks CF, Dye C, De Cock KM, Williams BG. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet. 2009;373(9657):48–57.PubMedCrossRefGoogle Scholar
  84. 84.
    Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. 2010. http://aidsinfo.nih.gov/contentfiles/PerinatalGL.pdf
  85. 85.
    Wheeler WH, Ziebell RA, Zabina H, Pieniazek D, Prejean J, Bodnar UR, et al. Prevalence of transmitted drug resistance associated mutations and HIV-1 subtypes in new HIV-1 diagnoses, U.S.-2006. AIDS. 2010;24(8):1203–12.PubMedCrossRefGoogle Scholar
  86. 86.
    Wensing AM, van de Vijver DA, Angarano G, Asjo B, Balotta C, Boeri E, et al. Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: implications for clinical management. J Infect Dis. 2005;192(6):958–66.PubMedCrossRefGoogle Scholar
  87. 87.
    Wittkop L, Gunthard HF, de Wolf F, Dunn D, Cozzi-Lepri A, de Luca A, et al. Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study. Lancet Infect Dis. 2011;11(5):363–71.PubMedCrossRefGoogle Scholar
  88. 88.
    Boden D, Hurley A, Zhang L, Cao Y, Guo Y, Jones E, et al. HIV-1 drug resistance in newly infected individuals. JAMA. 1999;282(12):1135–41.PubMedCrossRefGoogle Scholar
  89. 89.
    Simon V, Vanderhoeven J, Hurley A, Ramratnam B, Louie M, Dawson K, et al. Evolving patterns of HIV-1 resistance to antiretroviral agents in newly infected individuals. AIDS. 2002;16(11):1511–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Shet A, Berry L, Mohri H, Mehandru S, Chung C, Kim A, et al. Tracking the prevalence of transmitted antiretroviral drug-resistant HIV-1: a decade of experience. J Acquir Immune Defic Syndr. 2006;41(4):439–46.PubMedCrossRefGoogle Scholar
  91. 91.
    Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, Berger DS, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009;374(9692):796–806.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Infectious Diseases, Cancer InstituteNew York University School of MedicineNew YorkUSA
  2. 2.Aaron Diamond AIDS Research Center, an affiliate of the Rockefeller UniversityNew YorkUSA

Personalised recommendations