HIV suppression in lymphoid tissue varies with antiretroviral regimen
Antiretroviral therapy comprising two nucleoside reverse transcriptase inhibitors (NRTI)and a protease inhibitor is more effective in reducing viral burden in lymphoid tissue than two NRTIs alone or two NRTIs with nevirapine, European investigators report.
In a study reported in the August 17th issue of AIDS, three patients were treated with two NRTIs, 11 were treated with two NRTIs plus a protease inhibitor, and 16 were treated with two NRTIs plus nevirapine.All patients had maintained a plasma viral load of <20 copies/mL within the previous 6 months.
Dr.Esteban Marténez of the Hospital Clínic Universitari in Barcelona, Spain and colleagues performed tonsillar biopsies to measure viral load, in which the limit of quantification was 100 copies RNA/mg tissue.
Undetectable tonsillar viral load was observed in 10 of 11 patients treated with a rotease inhibitor, 10 of 16 treated with nevirapine, and in zero of three patients treated with 2 NRTIs alone.
Among those with detectable virus in tonsillar tissue, 488 copies/mg tissue were measured in the patient taking a protease inhibitor, 613 to 33, 077 copies/mg in those using nevirapine, and 16, 000 to 133, 000 copies/mg for those taking two.
After a median of 9 months, six of the 10 patients with detectable virus in tonsillar tissue experienced viral load rebound in plasma, compared with one out of the 20 with undetectable tonsillar virus.
Dr. Martinez and his associates conclude that antiretroviral regimens containing a protease inhibitor lead to better suppression of HIV replication in lymphoid tissue, which in turn keeps plasma viral loads under control for longer periods.
Although nevirapine was the NNRTI used in this study a previous study of lymph node virus burden compared the NNRTI efavirenz to PI (Dybul, JID 2000 Apr;181(4):1273-9).Detectable HIV RNA by nucleic acid sequence based amplification in lymph node mononuclear cells was found in similar numbers between those receiving efavirenz and those receiving PI.We cannot, however, conclude that efavirenz is, therefore, more potent than nevirapine until a comparison of the two NNRTI ‘s is made in a single study using the same methodology.
Lymphoid tissue is the most important reservoir of HIV and even after prolonged periods of undetectable plasma viraemia there is evidence of residual viral replication and latent infection with replicative competent virus in lymphoid tissue.Consequently, regimens with a better response in lymphoid tissue may be given priority if these preliminary results from pilot studies can be confirmed in randomised trials.
One such trial is already ongoing, the Atlantic study in which a triple regimen including didanosine and stavudine plus indinavir, nevirapine or a third nucleoside analogue (lamivudine)are compared.Preliminary data from this study suggest a worse virological response in the triple nucleoside arm both in plasma and in lymphoid tissue.Additionally, regimens may vary in their impact on the overall structure and immunological function of lymphoid tissue.
Preliminary data from the Atlantic study reported at the 1 st IAS conference in Buenos Aires this summer revealed such differences amongst those receiving triple nucleoside analogue (monoclass)and either PI or NNRTI based combinations (dual class).Despite plasma viral load markers of successful therapy follicular hyperplasia and p24 antigen expression was seen among persons randomised to triple nucleoside analogue therapy.Significant abnormalities persisted in all lymphoid tissues but especially among patients receiving 3 NA.
Such quantitative and qualitative differences in both virological and immunological response to the various classes of antiretroviral drugs is deserving of further investigation.Despite parity of short term plasma viral load response not all regimens may be considered equal in efficacy.Such differences may be of crucial importance in the long term administration of these agents which is an unfortunate feature of the current treatment of HIV-infection.
Martinez E et al.Lymphoid tissue viral burden and duration of viral suppression in plasma.AIDS 2001;15:1477-1482. Source:Reuters Health