, EDITORIAL Retroviruses & Opportunistic Infections '99 Itis impossible to condense the plethora of informa- tion presented on antietcoviral therapy at the 6H Conference on Retroviruses and Opportunistic Infections, eld from January 31-February 4 1999 in Chicago toa single and simple message ‘A the Vancouver International AIDS Conference held ess than 3 years ago, the predominant theme repeated on the front pages of newspapers ll over the word was that triple drug therapy (now unfortunately known as HAART 0: highly active antiretroviral therapy) was vastly superior t prior approaches tothe treatment of HIV-1 infection. ft would tun this disease into a manageable chronic infection, and in some minds the eradication of HIV was ust around the corner. OF cours, the story had to become more complex overtime and the material presented atthe Chicago meeting sa refection of that. What follows isa brief and cclectic selection of some ‘highlights. "A numberof comparative stuls in antiretroviral nave subjects was presented which indicate that antiviral efficacy and C4 cell esponses obtained with combinations of thre reverse transcriptase inhibitors may be equivalent to those of combinations of two nucleoside analogues and a protease inhibitor [1-3]. Follow-up of these studies, however, is stil relatively short and no information has yet been obtained on their relative potency in suppressing HN load in lymphatic tissues. On aditferent note, these randomized studies present a unique opportunity to study the reative contribution of eiferent antietroviras tothe now widely prevailing syndrome of ipodystophy in patients who have received long-term therapy. In line with earlier publications [4-7], data were presented showing that even with prolonged suppres- sion of plasma HIV-1 levels to below the detection limit of utrasensitve assays (5-20 copies, theres discrete evidence of ongoing HI-1 replication 9 evidenced by low but discernable rates of nucleotide ‘sequence evolution [8] and the presence of HIV-1 RNA in lymphoid tissues, peripheral blood cells and genital secretions [8-10] nereasing the tuenover ofthe latently infected target cell population in the presence of currently available multidrug combinations [10,11} oe esa 43 may thus not be enough to eradicate MIV-1. Antiviral potency is still an isue of primary concern These observations reinforce the bind that we have created through use ofthe term HAART: Fist, not al 'WAART regimens are equivalent. Moreover, do these now have to be replaced by EMAART (even more active antiretroviral therapy)? And this by MEMAART (more than even more active antiretroviral therapy)? In seeming contrast with the above statement on ‘the overriding importance of antiviral poteney are the findings of sustained CD4 eell responses, and decreased CDé cell turnover as compared to untreated controls in people displaying virological failure during treatment with protease inhibitor-based regimens [12 This has been ascribed to lack of fitness of protease inhbitor-resistant HIV-1 [13]. However, @ more straightforward explanation may simply be the dsinhi- bition of the generation of lymphocytes from precursors even when suppression of HIV replication is not complete [14,15]. tis too early, however, to adopt continuation of drug regimens that fail to suppress HIV-1 plasma levels to below the limits of detection as the strategy of choice in patients who still have other antiretroviral drug options. t ean be predicted that, eventually, with ongoing high-level replication, the Virus will acquire compensatory mutations that will restore fitness, with predictable consequences Joep MA Lange and Douglas D Richman Editors-in-Chief References 1. Kavlama C, Murphy R, Joon V ea The Aeletic Studysa enndoonteed open-label study comparing two trots bioe @lfsparig sate ena ca ard PL containing regimen. eth Conference on Retrouirases and Opporuusisic Infections, Chicago, January 31-February 4 199%; Abstrace 18 2, Stasaewal 8, Kesee®, Gathe] etal ZiagenfCombivie is equivalent eo indinavilcombivie in antiretroviral therapy naive adults at 24 weeks. th Conference on KRetroutruses and Opportunistic Infections, Chicago, Juacy Si-Bebrny 41999; Abaract 20 taka K Sinem Sei to A phe smultcente, randomized, open-label study 9 compare the anirewoviral activity and tolerability of elavicens (EEV} + indinavir (DV), versus FFV + zidovudine. (ZDV)'s lamivudine (1C), vers IDV + ZDV 4 STCar 48 weeks (Study DMP 266-006), 6th Conference on Retroviruses and Opportunistic Inectionn Chicas, January 31-Febrogry 4 1999 Abstract TB16 (Chun TW, Carruth I, FingiB etal. Quantification of latent tase reservoir’ and total bay vial loa iy HIV infection. Nature 1997, 3897-183 188 Wong IK, Hlezarch M, Guinthard HIP etal. Recovery of repliation-competent HIV despite prolonged soprres son of plasma viremia Science 1997. 278 129 1e 385, Fina, Hetmankova M, Pierson T af ldcattieatn ofa reservoir for HIV-1 i patients om highly seve, antiretrovical therapy. Sconce 1997, 37881295 1300, Chun EW, Suuyver ty Mizell Sb et Presence of oo inducible FIV-1 latest teseroir during highly serie Aanttetroviral therapy. Proceedings of the Wanional Academy of Sciences, USA 19975 94003195 15199, Wong J, Ganthard H, Fiscus § ef al. Residual HIV RNA and DNA in mph tode and HIV RNA dn genital secretions anid in CSE afer two years of ‘gopreson of emia nthe Mes OBS coke. 6th Conference an Retroviruse and Opportunist Infections, Chicago, January 31-Pebruary 4 1999; eset 7 7 umuriaga K. Pediatric antiretroviral therapy. 6 Conference on Retrouiuses and Opportunti Infections, Cheago, january H1-Pebtuary 4 1999; Abstract 12 Prins Jy Jurriaans S, van Praag R etal. OKT3 and rh i 12, 2B. 14, 11-2 in HVA patients on HAART with prolonged suppression of pasina viremia, Gib Convenes Retroviruses and Opportunistic Infecions Chicago, January 3t-Februay@ 1995 Abstract 1 ‘Ghun Fe, Engel, Mizell Hier LA 8 Fauci AS. Induction of HIV-t epison in ltenely eed Chas T als usng a combination of evokes fou of Experimental Medicine 1958: 1888-91 Deeks, Hoh’, anley MB eral, reall emevcs Kinetics in patents with a sstined CD cll capone after experiencing virologic falure of 1 prosease inhibitor based seximen, Sth Conferene on Retroviruses and Opportunistic ifectona, Chicago, Jesuary 31-February 4 1999; Abstract TR Stoddart C Mammang f Moreno M fa Lack of fitness of protease inhibicoresitant HIV ri. 6th Conference on Retroviruses and Opportnistie Ipfetons Chtcagy January 51-Rebroary 4 1999 bstesct {Gark'DR, Reppig 5, Pakker NG, Prins JM, Danner SA, Lange JMA 8° Miedeme Fel egewal immplted in HIV-1 infected snivduale th Conference on Retroviruses and Opportnttic Infections, Chica Joeusey 31-Rebraary 4 1999" Abeer MeCine JT cell production in AV disease. 6th Confereice on Relroviass and Opportnteg Infections, Chicago, January 31-Reeruary 4 1999, Abserace 3. ° ©1889 eatin! Mesa Pes