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Pilot study of a combination of highly active antiretroviral therapy and cytokines to induce HIV-1 remission.
J Acquir Immune Defic Syndr 2001; 26(1):44-55JA

Abstract

A pilot study of a combination of highly active antiretroviral therapy (HAART) and cytokines in early HIV-1 infection has been undertaken to test the hypothesis that HIV-1 remission can be reached with this strategy by flushing latently infected viral reservoirs. Ten previously antiretroviral naive patients have received a combination of zidovudine, lamivudine, didanosine, saquinavir, and ritonavir for 72 weeks. Between weeks 12 and 48, three courses of interleukin (IL)-2 (7.5 millions of international units [MUI] twice a day for 5 consecutive days) and 2 courses of gamma-interferon (IFN) (100 microg every other day during 2 weeks) were administered subcutaneously. All patients reached plasma HIV-1 RNA levels < 20 copies/ml within 12 +/- 4 weeks. Transient increases in plasma levels (< 120 copies/ml) were observed during administration of IL-2, but less frequently during gamma-IFN administration. HIV-1 RNA decreased in lymph node cells by approximately 4 log, then remained stable after week 24. A mean drop of -0.8 log in peripheral blood mononuclear cell (PBMC) proviral DNA was observed during the trial. Isolation of potentially infectious HIV-1 was successful in each case by coculture of CD4+ T cells taken at week 72. The 2 patients who stopped therapy at the end of the trial showed rebounding plasma HIV-1 RNA levels within a few weeks. No additional mutations were selected in comparison with those present at baseline in 8 patients. In addition, 2 patients developed new mutations in the reverse transcriptase or protease gene and in 1 case, resistance selection was found in lymphoid tissue HIV-1 RNA but not in latently infected cells. In all cases, a rapid increase in both naive and memory CD4+ T cells was observed, with a reduction in activation markers and preservation of the CD8+CD28+ subset. Consequently, an aggressive regimen of HAART and cytokines administered in early stage disease is associated with a positive effect in terms of proviral load reduction and immune reconstitution but is unable to induce HIV-1 remission, allowing low levels of viral replication to persist in lymphoid reservoirs.

Authors+Show Affiliations

Department of Infectious Diseases, Laboratory of Virology, and Immunology Laboratory; General Hospital, Toulon, France. avps@club-internet.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

11176268

Citation

Lafeuillade, A, et al. "Pilot Study of a Combination of Highly Active Antiretroviral Therapy and Cytokines to Induce HIV-1 Remission." Journal of Acquired Immune Deficiency Syndromes (1999), vol. 26, no. 1, 2001, pp. 44-55.
Lafeuillade A, Poggi C, Chadapaud S, et al. Pilot study of a combination of highly active antiretroviral therapy and cytokines to induce HIV-1 remission. J Acquir Immune Defic Syndr. 2001;26(1):44-55.
Lafeuillade, A., Poggi, C., Chadapaud, S., Hittinger, G., Chouraqui, M., Pisapia, M., & Delbeke, E. (2001). Pilot study of a combination of highly active antiretroviral therapy and cytokines to induce HIV-1 remission. Journal of Acquired Immune Deficiency Syndromes (1999), 26(1), pp. 44-55.
Lafeuillade A, et al. Pilot Study of a Combination of Highly Active Antiretroviral Therapy and Cytokines to Induce HIV-1 Remission. J Acquir Immune Defic Syndr. 2001 Jan 1;26(1):44-55. PubMed PMID: 11176268.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pilot study of a combination of highly active antiretroviral therapy and cytokines to induce HIV-1 remission. AU - Lafeuillade,A, AU - Poggi,C, AU - Chadapaud,S, AU - Hittinger,G, AU - Chouraqui,M, AU - Pisapia,M, AU - Delbeke,E, PY - 2001/2/15/pubmed PY - 2001/3/10/medline PY - 2001/2/15/entrez SP - 44 EP - 55 JF - Journal of acquired immune deficiency syndromes (1999) JO - J. Acquir. Immune Defic. Syndr. VL - 26 IS - 1 N2 - A pilot study of a combination of highly active antiretroviral therapy (HAART) and cytokines in early HIV-1 infection has been undertaken to test the hypothesis that HIV-1 remission can be reached with this strategy by flushing latently infected viral reservoirs. Ten previously antiretroviral naive patients have received a combination of zidovudine, lamivudine, didanosine, saquinavir, and ritonavir for 72 weeks. Between weeks 12 and 48, three courses of interleukin (IL)-2 (7.5 millions of international units [MUI] twice a day for 5 consecutive days) and 2 courses of gamma-interferon (IFN) (100 microg every other day during 2 weeks) were administered subcutaneously. All patients reached plasma HIV-1 RNA levels < 20 copies/ml within 12 +/- 4 weeks. Transient increases in plasma levels (< 120 copies/ml) were observed during administration of IL-2, but less frequently during gamma-IFN administration. HIV-1 RNA decreased in lymph node cells by approximately 4 log, then remained stable after week 24. A mean drop of -0.8 log in peripheral blood mononuclear cell (PBMC) proviral DNA was observed during the trial. Isolation of potentially infectious HIV-1 was successful in each case by coculture of CD4+ T cells taken at week 72. The 2 patients who stopped therapy at the end of the trial showed rebounding plasma HIV-1 RNA levels within a few weeks. No additional mutations were selected in comparison with those present at baseline in 8 patients. In addition, 2 patients developed new mutations in the reverse transcriptase or protease gene and in 1 case, resistance selection was found in lymphoid tissue HIV-1 RNA but not in latently infected cells. In all cases, a rapid increase in both naive and memory CD4+ T cells was observed, with a reduction in activation markers and preservation of the CD8+CD28+ subset. Consequently, an aggressive regimen of HAART and cytokines administered in early stage disease is associated with a positive effect in terms of proviral load reduction and immune reconstitution but is unable to induce HIV-1 remission, allowing low levels of viral replication to persist in lymphoid reservoirs. SN - 1525-4135 UR - https://www.unboundmedicine.com/medline/citation/11176268/Pilot_study_of_a_combination_of_highly_active_antiretroviral_therapy_and_cytokines_to_induce_HIV_1_remission_ L2 - http://Insights.ovid.com/pubmed?pmid=11176268 DB - PRIME DP - Unbound Medicine ER -