Triple therapy with AZT and 3TC in combination with nelfinavir mesylate in 12 antiretroviral-naive subjects chronically infected with HIV-1.
Int Conf AIDS 1996 Jul 7-12; 11:28 (abstract no. LB.B.6031) Markowitz M, Cao Y, Hurley A, O'Donovan R, Peterkin J, Anderson B, Smiley L, Keller A, Johnson P, Johnson D, Ho DD; The Aaron Diamond AIDS Research Center, New York, NY. Fax: (212) 725-1126. E-mail: marty@adarc.nyu.edu.
Triple therapy with 2 nucleoside RT inhibitors and a potent protease inhibitor may erect an antiviral barrier such that durable suppression of measurable viral replication occurs. This, in turn, should result in long-term immunologic benefit. To test this hypothesis, 12 antiretroviral-naive HIV-infected subjects with a screening plasma viremia of greater than 10,000 copies/ml were begun on AZT 200 mg TID/3TC 150 mg BID/nelfinavir 750 mg TID. Baseline median and mean log plasma RNA were 4.91 and 5.32 respectively. CD4 cell counts at baseline ranged from 37 to 557 cells/mm3 with median and mean values of 253 and 258 cells/mm3 respectively. This triple regimen has been well tolerated with mild to moderate diarrhea, mild to moderate nausea, and fatigue being the most common drug related adverse events. 1 of 12 withdrew due to Grade 4 elevation of CPK and moderate diarrhea associated with abdominal cramping. Aviremia (less than 500 RNA copies/ml) and negativity in PBMC co-cultures (less than .1 TCID (50)/10(6) PBMC) have been achieved in all remaining 11 subjects by week 12 of therapy, with a mean reduction in log plasma RNA of 2.62. Following the predicted 2.0 log reduction in plasma RNA in the first 2-3 weeks, the second phase
of viral decay was slower with a mean T (+) of approximately 17 days. Associated with this degree of suppression of viral replication, a mean and median increase of 109 and 98 cells/mm (3) is observed at 12 weeks. We conclude that triple therapy with AZT, 3TC, and nelfinavir mesylate results in uniform aviremia after three months of uninterrupted therapy, and holds promise in pharmacologically controlling HIV replication in a human host.
