Skip to main content

Advertisement

Log in

Virologic and immunologic response to highly active antiretroviral therapy

  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

Highly active antiretroviral therapy (HAART) delays clinical progression by suppressing viral replication, measured by a substantial reduction in HIV RNA, allowing the immune system to reconstitute, measured in most studies by an increase in CD4 cells. These virologic and immunologic consequences do not occur uniformly among HAART users. Markers of HIV disease stage at the time of HAART initiation are critical determinants of the progression while receiving HAART. In this report, we review studies describing the heterogeneous virologic and immunologic progression after the initiation of HAART, discuss methodologic concerns in the study of the response of biomarkers, and update findings obtained in the Multicenter AIDS Cohort Study, which show that CD4 cell count, history of antiretroviral therapy, and age at the time of initiation are independent determinants of response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Detels R, Munoz A, McFarlane G, et al.: Effectiveness of potent antiretroviral therapy on time to AIDS and death in men with known HIV infection duration. JAMA 1998, 280:1497–1503.

    Article  PubMed  CAS  Google Scholar 

  2. Hogg RS, Heath KV, Yip B, et al.: Improved survival among HIV-infected individuals following initiation of antiretroviral therapy. JAMA 1998, 279:450–454.

    Article  PubMed  CAS  Google Scholar 

  3. Jacobson LP, Li R, Phair J, et al.: Evaluation of the effectiveness of highly active antiretroviral therapy in persons with human immunodeficiency virus using biomarker-based equivalence of disease progression. Am J Epidemiol 2002, 155:760–770.

    Article  PubMed  CAS  Google Scholar 

  4. Tarwater PM, Margolick JB, Jin J, et al.: Increase and plateau of CD4 T-cell counts in the 3-1/2 years after initiation of potent antiretroviral therapy. J Acquir Immune Defic Syndr 2001, 27:168–175.

    PubMed  CAS  Google Scholar 

  5. Casado JL, Perez-Elias MJ, Antela A, et al.: Predictors of longterm response to protease inhibitor therapy in a cohort of HIV-infected patients. AIDS 1998, 12:F131-F135.

    Article  PubMed  CAS  Google Scholar 

  6. Yamashita TE, Phair JP, Munoz A, et al.: Immunologic and virologic response to highly active antiretroviral therapy in the Multicenter AIDS Cohort Study. AIDS 2001, 15:735–746. An earlier analysis of short- and long-term HIV RNA and CD4 cell count response to HAART in MACS, which showed that best response was seen among patients without experience to any component of HAART. Baseline CD4 cell count was a predictor of response and age effects were restricted to early recovery of CD4 cells after HAART initiation.

    Article  PubMed  CAS  Google Scholar 

  7. Kleeberger CA, Phair JP, Strathdee SA, et al.: Determinants of heterogeneous adherence to HIV-antiretroviral therapies in the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr 2001, 26:82–92.

    PubMed  CAS  Google Scholar 

  8. Le Moing V, Chene G, Carrieri MP, et al.: Clinical, biologic, and behavioral predictors of early immunologic and virologic response in HIV-infected patients initiating protease inhibitors. J Acquir Immune Defic Syndr 2001, 27:372–376.

    PubMed  Google Scholar 

  9. Lu W, Andrieu JM: HIV protease inhibitors restore impaired T-cell proliferative response in vivo and in vitro: a viralsuppression-independent mechanism. Blood 2000, 96:250–258.

    PubMed  CAS  Google Scholar 

  10. Mocroft A, Devereux H, Kinloch-de-Loes S, et al.: Immunological, virological and clinical response to highly active antiretroviral therapy treatment regimens in a complete clinic population. Royal Free Centre for HIV Medicine. AIDS 2000, 14:1545–1552.

    Article  PubMed  CAS  Google Scholar 

  11. Touloumi G, Paparizos V, Sambatakou H, et al.: Virological and immunological response to HAART therapy in a community-based cohort of HIV-1-positive individuals. HIV Clin Trials 2001, 2:6–16.

    Article  PubMed  CAS  Google Scholar 

  12. Phillips AN, Staszewski S, Weber R, et al.: HIV viral load response to antiretroviral therapy according to the baseline CD4 cell count and viral load. JAMA 2001, 286:2560–2567.

    Article  PubMed  CAS  Google Scholar 

  13. Bangsberg DR, Charlebois ED, Grant RM, et al.: High levels of adherence do not prevent accumulation of HIV drug resistance mutations. AIDS 2003, 17:1925–1932.

    Article  PubMed  Google Scholar 

  14. Gallego O, de Mendoza C, Perez-Elias MJ, et al.: Drug resistance in patients experiencing early virological failure under a triple combination including indinavir. AIDS 2001, 15:1701–1706.

    Article  PubMed  CAS  Google Scholar 

  15. Grant RM, Hecht FM, Warmerdam M, et al.: Time trends in primary HIV-1 drug resistance among recently infected persons. JAMA 2002, 288:181–188.

    Article  PubMed  CAS  Google Scholar 

  16. Perno CF, Cozzi-Lepri A, Balotta C, et al.: Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy. J Infect Dis 2001, 184:983–991.

    Article  PubMed  CAS  Google Scholar 

  17. Carrieri P, Cailleton V, Le Moing V, et al.: The dynamic of adherence to highly active antiretroviral therapy: results from the French National APROCO cohort. J Acquir Immune Defic Syndr 2001, 28:232–239.

    PubMed  CAS  Google Scholar 

  18. DeMasi RA, Graham NM, Tolson JM, et al.: Correlation between self-reported adherence to highly active antiretroviral therapy (HAART) and virologic outcome. Adv Ther 2001, 18:163–173.

    PubMed  CAS  Google Scholar 

  19. Knobel H, Guelar A, Carmona A, et al.: Virologic outcome and predictors of virologic failure of highly active antiretroviral therapy containing protease inhibitors. AIDS Patient Care STDS 2001, 15:193–199.

    Article  PubMed  CAS  Google Scholar 

  20. Walsh JC, Pozniak AL, Nelson MR, et al.: Virologic rebound on HAART in the context of low treatment adherence is associated with a low prevalence of antiretroviral drug resistance. J Acquir Immune Defic Syndr 2002, 30:278–287.

    PubMed  CAS  Google Scholar 

  21. Ahdieh L, Gange SJ, Greenblatt R, et al.: Selection by indication of potent antiretroviral therapy use in a large cohort of women infected with human immunodeficiency virus. Am J Epidemiol 2000, 152:923–933.

    Article  PubMed  CAS  Google Scholar 

  22. Bratt G, Karlsson A, Leandersson AC, et al.: Treatment history and baseline viral load, but not viral tropism or CCR-5 genotype, influence prolonged antiviral efficacy of highly active antiretroviral treatment. AIDS 1998, 12:2193–2202.

    Article  PubMed  CAS  Google Scholar 

  23. Brumme ZL, Chan KJ, Dong W, et al.: CCR5 2 and promoter polymorphisms are not correlated with initial virological or immunological treatment response. AIDS 2001, 15:2259–2266.

    Article  PubMed  CAS  Google Scholar 

  24. Guerin S, Meyer L, Theodorou I, et al.: CCR5 32 deletion and response to highly active antiretroviral therapy in HIV-1-infected patients. AIDS 2000, 14:2788–2790.

    Article  PubMed  CAS  Google Scholar 

  25. Valdez H, Purvis SF, Lederman MM, et al.: Association of the CCR5D32 mutation with improved response to antiretroviral therapy. JAMA 1999, 282:734.

    Article  PubMed  CAS  Google Scholar 

  26. O’Brien TR, McDermott DH, Ioannidis JP, et al.: Effect of chemokine receptor gene polymorphisms on the response to potent antiretroviral therapy. AIDS 2000, 14:821–826.

    Article  PubMed  CAS  Google Scholar 

  27. Lathey JL, Tierney C, Chang SYP, et al.: Associations of CCR5, CCR2, and stromal cell-derived factor 1 genotypes with human immunodeficiency virus disease progression in patients receiving nucleoside therapy. J Infect Dis 2001, 184:1402–1411.

    Article  PubMed  CAS  Google Scholar 

  28. Silverberg MJ, Smith MW, Chmiel JS, et al.: Fraction of cases of acquired immunodeficiency syndrome prevented by the interactions of identified restriction gene variants. Am J Epidemiol 2004, 159:232–241.

    Article  PubMed  CAS  Google Scholar 

  29. Mocroft A, Ruiz L, Reiss P, et al.: Virological rebound after suppression on highly active antiretroviral therapy. AIDS 2003, 17:1741–1751.

    Article  PubMed  Google Scholar 

  30. Le Moing V, Chene G, Carrieri MP, et al.: Predictors of virological rebound in HIV-1-infected patients initiating a protease inhibitor-containing regimen. AIDS 2002, 16:21–29.

    Article  Google Scholar 

  31. Paredes R, Mocroft A, Kirk O, et al.: Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe: results from the EuroSIDA study. Arch Intern Med 2000, 160:1123–1132.

    Article  PubMed  CAS  Google Scholar 

  32. Jacobson LP, Phair JP, Yamashita TE: Virologic and immunologic response to highly active antiretroviral therapy. Curr Infect Dis Rep 2002, 4:88–96.

    PubMed  Google Scholar 

  33. Miller V, Staszewski S, Sabin C, et al.: CD4 lymphocyte count as a predictor of the duration of highly active antiretroviral therapy-induced suppression of human immunodeficiency virus load. J Infect Dis 1999, 180:530–533.

    Article  PubMed  CAS  Google Scholar 

  34. Abgrall S, Duval X, Joly V, et al.: Clinical and immunologic outcome in patients with human immunodeficiency virus infection, according to virologic efficacy in the year after virus undetectability, during antiretroviral therapy. Clin Infect Dis 2003, 37:1517–1526.

    Article  PubMed  Google Scholar 

  35. Anastos K, Barron Y, Cohen MH, et al.: The prognostic importance of changes in CD4+ cell count and HIV-1 RNA level in women after initiating highly active antiretroviral therapy. Ann Intern Med 2004, 140:256–264.

    PubMed  CAS  Google Scholar 

  36. Bahrani A, Ramaswamy R, Oldfield EC3rd: Effects of virologic rebound on CD4 cell counts. Clin Infect Dis 2001, 32:1231–1232.

    Article  PubMed  CAS  Google Scholar 

  37. Deeks SG, Barbour JD, Martin JN, et al.: Sustained CD4+ T cell response after virologic failure of protease inhibitor-based regimens in patients with human immunodeficiency virus infection. J Infect Dis 2000, 181:946–953.

    Article  PubMed  CAS  Google Scholar 

  38. Hejdeman B, Lenkei R, Leandersson AC, et al.: Clinical and immunological benefits from highly active antiretroviral therapy in spite of limited viral load reduction in HIV type 1 infection. AIDS Res Hum Retroviruses 2001, 17:277–286.

    Article  PubMed  CAS  Google Scholar 

  39. DeHovitz JA, Kovacs A, Feldman JG, et al.: The relationship between virus load response to highly active antiretroviral therapy and change in CD4 cell counts: a report from the Women’s Interagency HIV study. J Infect Dis 2000, 182:1527–1530.

    Article  PubMed  CAS  Google Scholar 

  40. Goetz MB, Boscardin WJ, Wiley D, Alkasspooles S: Decreased recovery of CD4 lymphocytes in older HIV-infected patients beginning highly active antiretroviral therapy. AIDS 2001, 15:1576–1579.

    Article  PubMed  CAS  Google Scholar 

  41. Greub G, Ledergerber B, Battegay M, et al.: Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study. Lancet 2000, 356:1800–1805.

    Article  PubMed  CAS  Google Scholar 

  42. Viard JP, Mocroft A, Chiesi A, et al.: Influence of age on CD4 cell recovery in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy: evidence from the EuroSIDA study. J Infect Dis 2001, 183:1290–1294.

    Article  PubMed  CAS  Google Scholar 

  43. Pakker NG, Kroon ED, Roos MT, et al.: Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group. AIDS 1999, 13:203–212. A report from the EuroSIDA Study Group showing that the increase in CD4 cell counts in the 3 years after HAART initiation occurred more rapidly among younger participants.

    Article  PubMed  CAS  Google Scholar 

  44. Kaufmann GR, Perrin L, Pantaleo G, et al.: CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med 2003, 163:2187–2195. A report from the Swiss HIV Cohort Study in which younger age was associated with better CD4 response among those patients with advanced disease. A lack of sustained HIV-RNA suppression, treatment interruptions, and older age were associated with a poorer CD4 T-cell response within 4 years after HAART initiation.

    Article  PubMed  Google Scholar 

  45. Teixeira L, Valdez H, McCune JM, et al.: Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function. AIDS 2001, 15:1749–1756.

    Article  PubMed  CAS  Google Scholar 

  46. Douek DC, McFarland RD, Keiser PH, et al.: Changes in thymic function with age and during the treatment of HIV infection. Nature 1998, 396:690–695.

    Article  PubMed  CAS  Google Scholar 

  47. Haynes BF, Hale LP, Weinhold KJ, et al.: Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection. J Clin Invest 1999, 103:453–460.

    Article  PubMed  CAS  Google Scholar 

  48. Deeks SG, Barbour JD, Grant RM, Martin JN: Duration and predictors of CD4 T-cell gains in patients who continue combination therapy despite detectable plasma viremia. AIDS 2002, 16:201–207. A clinic cohort study showing that among those patients with virologic failure but good CD4 response after HAART initiation, approximately 50% of the participants experienced a subsequent decrease in CD4 cell counts to pretherapy levels by 3 years after virologic failure. Change in HIV RNA from pretreatment levels and discontinuing therapy were independent predictors of subsequent CD4 decline among these individuals with discordant responses.

    Article  PubMed  Google Scholar 

  49. Antinori A, Liuzzi G, Cingolani A, et al.: Drug-resistant mutants of HIV-1 in patients exhibiting increasing CD4 cell count despite virological failure of highly active antiretroviral therapy. AIDS 2001, 15:2325–2327.

    Article  PubMed  CAS  Google Scholar 

  50. Dronda F, Moreno S, Moreno A, et al.: Long-term outcomes among antiretroviral-naive human immunodeficiency virus-infected patients with small increases in CD4+ cell counts after successful virologic suppression. Clin Infect Dis 2002, 35:1005–1009

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jacobson, L.P., Phair, J.P. & Yamashita, T.E. Virologic and immunologic response to highly active antiretroviral therapy. Curr HIV/AIDS Rep 1, 74–81 (2004). https://doi.org/10.1007/s11904-004-0011-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11904-004-0011-1

Keywords

Navigation