Overshoot of HIV-1 viraemia after early discontinuation of antiretroviral treatment - PubMed (original) (raw)
Overshoot of HIV-1 viraemia after early discontinuation of antiretroviral treatment
M D de Jong et al. AIDS. 1997 Sep.
Abstract
Objective: To determine whether, as predicted by predator-prey dynamics, early withdrawal of antiretroviral therapy, i.e. when the number of CD4+ lymphocytes is still elevated, results in an overshoot of HIV-1 viraemia due to infection of increased numbers of available target cells at that time.
Design and methods: Five HIV-1-infected individuals were identified who discontinued antiretroviral therapy for various reasons after 8-19 days, and from whom stored serum samples obtained before, during, and shortly after treatment were available for measurement of HIV-1 RNA load. A mathematical model was designed to assess whether increased target cell availability could quantitatively explain the clinical observations.
Results: After therapy withdrawal, increases in the HIV-1 RNA load to levels exceeding pretreatment values by log10 0.6-1.5 copies/ml were observed after 2-17 days in all four of the individuals who had treatment-induced increases in CD4+ cell counts at the time of therapy withdrawal. Increases in viraemia were maximal within a few days, and subsequently seemed to wane until the pretreatment equilibrium between virus and its target cells was attained. Mathematical modelling confirms that these transient increases in viraemia can be explained by increased availability of target cells at the time of therapy withdrawal.
Conclusions: Transient rises in HIV-1 viraemia do occur following early therapy withdrawal. These rises especially warrant consideration in short-term antiretroviral regimens for prevention of mother-to-child transmission, as are being studied in developing countries, since they could result in an increased transmission risk during the post-partum period through breast-feeding. This possibility needs to be investigated urgently.
Similar articles
- Effect of GB virus C on response to antiretroviral therapy in HIV-infected Brazilians.
Souza IE, Zhang W, Diaz RS, Chaloner K, Klinzman D, Stapleton JT. Souza IE, et al. HIV Med. 2006 Jan;7(1):25-31. doi: 10.1111/j.1468-1293.2005.00339.x. HIV Med. 2006. PMID: 16313289 Clinical Trial. - Six-year follow-up of HIV-1-infected adults in a clinical trial of antiretroviral therapy with indinavir, zidovudine, and lamivudine.
Gulick RM, Meibohm A, Havlir D, Eron JJ, Mosley A, Chodakewitz JA, Isaacs R, Gonzalez C, McMahon D, Richman DD, Robertson M, Mellors JW. Gulick RM, et al. AIDS. 2003 Nov 7;17(16):2345-9. doi: 10.1097/00002030-200311070-00009. AIDS. 2003. PMID: 14571186 Clinical Trial. - Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response. ACTG 241 Protocol Virology Substudy Team.
Hughes MD, Johnson VA, Hirsch MS, Bremer JW, Elbeik T, Erice A, Kuritzkes DR, Scott WA, Spector SA, Basgoz N, Fischl MA, D'Aquila RT. Hughes MD, et al. Ann Intern Med. 1997 Jun 15;126(12):929-38. doi: 10.7326/0003-4819-126-12-199706150-00001. Ann Intern Med. 1997. PMID: 9182469 Clinical Trial. - Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection.
Siegfried N, van der Merwe L, Brocklehurst P, Sint TT. Siegfried N, et al. Cochrane Database Syst Rev. 2011 Jul 6;(7):CD003510. doi: 10.1002/14651858.CD003510.pub3. Cochrane Database Syst Rev. 2011. PMID: 21735394 Review. - Molecular biological assessment methods and understanding the course of the HIV infection.
Katzenstein TL. Katzenstein TL. APMIS Suppl. 2003;(114):1-37. APMIS Suppl. 2003. PMID: 14626050 Review.
Cited by
- Recent developments of nanotherapeutics for targeted and long-acting, combination HIV chemotherapy.
Gao Y, Kraft JC, Yu D, Ho RJY. Gao Y, et al. Eur J Pharm Biopharm. 2019 May;138:75-91. doi: 10.1016/j.ejpb.2018.04.014. Epub 2018 Apr 17. Eur J Pharm Biopharm. 2019. PMID: 29678735 Free PMC article. Review. - [Study of factors related to adherence to antiretroviral therapy among patients followed at HIV/AIDS Unit in the District Hospital of Dschang, Cameroon].
Mbopi-Kéou FX, Dempouo Djomassi L, Monebenimp F. Mbopi-Kéou FX, et al. Pan Afr Med J. 2012;12:55. Epub 2012 Jun 29. Pan Afr Med J. 2012. PMID: 22937195 Free PMC article. French. - Maternal CD4+ cell count decline after interruption of antiretroviral prophylaxis for the prevention of mother-to-child transmission of HIV.
Ekouevi D, Abrams EJ, Schlesinger M, Myer L, Phanuphak N, Carter RJ; MTCT-Plus Initiative. Ekouevi D, et al. PLoS One. 2012;7(8):e43750. doi: 10.1371/journal.pone.0043750. Epub 2012 Aug 27. PLoS One. 2012. PMID: 22952754 Free PMC article. Clinical Trial. - Viral Load Monitoring in HIV Infection.
Holodniy M. Holodniy M. Curr Infect Dis Rep. 1999 Dec;1(5):497-503. doi: 10.1007/s11908-999-0064-9. Curr Infect Dis Rep. 1999. PMID: 11095829 - Productive infection maintains a dynamic steady state of residual viremia in human immunodeficiency virus type 1-infected persons treated with suppressive antiretroviral therapy for five years.
Havlir DV, Strain MC, Clerici M, Ignacio C, Trabattoni D, Ferrante P, Wong JK. Havlir DV, et al. J Virol. 2003 Oct;77(20):11212-9. doi: 10.1128/jvi.77.20.11212-11219.2003. J Virol. 2003. PMID: 14512569 Free PMC article. Clinical Trial.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials