VIRACEPT COMBINATION IN PREGNANT WOMEN PREVENTS HIV INFECTION IN NEWBORNS, EARLY STUDY SHOWS

Another Study Highlights VIRACEPT As Part of Treatment for Young Children

SAN FRANCISCO 2 February, 2000 - Data were presented this week from the Pediatric AIDS Clinical Trials Group (PACTG) 353 study showing that anti-HIV combination therapy including the protease inhibitor VIRACEPT® (nelfinavir mesylate) in pregnant women prevented the transmission of HIV from mothers to their newborn children in all 8 participants who completed the trial. The PACTG 353 results, presented at the 7th Conference on Retroviruses and Opportunistic Infections in San Francisco, highlight the potential of protease inhibitor-containing regimens in further reducing the risk of vertical HIV transmission.

In addition to eliminating HIV transmission to the infants, the mothers in this study experienced significant benefits from treatment as well. Maternal levels of HIV viral load decreased significantly during the course of treatment, with a median decline from baseline to delivery of -1.8 log10 and from baseline to six weeks postpartum of -2.4 log10 (p=0.01). For 6 women (75%) in the trial, HIV viral load was below the level of quantification (<400 copies/mL) at delivery. Median maternal CD4 cell count at baseline was 220 cells/mm3, and increased to 308 and 415 cells/mm3 at delivery and six weeks postpartum, respectively.

HIV-infected pregnant women ranging from 14 to 34 weeks of gestation were enrolled in this trial and received oral doses of VIRACEPT 750mg three times daily (or TID) plus standard oral doses of the nucleoside analogues (NAs) AZT and 3TC, both during and after pregnancy. In labor, VIRACEPT and 3TC were administered orally, and AZT was administered intravenously.

In these preliminary results, treatment with VIRACEPT during pregnancy and in newborn infants appeared to be well-tolerated. The impact of gestational and postpartum treatment on HIV infection on mothers and newborns was also evaluated.

Of the 10 women enrolled, 8 completed the study and 2 did not carry to term for obstetrical reasons not related to treatment.

Newborn infants in this study received VIRACEPT (10mg/kg TID) in combination with weight-adjusted doses of AZT and 3TC. Treatment with VIRACEPT in the newborns appeared to be well-tolerated in these preliminary results. Transient decreases in hemoglobin and/or neutrophils were reported, which were resolved after discontinuation of AZT. At one week of life, the median VIRACEPT levels in infants were low, and further study of a higher dose (40 mg/kg BID) is underway.

All eight infants were born free of HIV infection at a median gestational age of 38 weeks (range 35-40 weeks). The HIV transmission rate (0%) seen in this trial appears to be lower than the transmission rate seen in trials of the current standard treatment with AZT alone to prevent mother-to-infant transmission (the ACTG 076 protocol), in which approximately 8% of infants were infected with HIV. However, the PACTG 353 study only studied 8 mother/infant pairs, and the duration of follow-up was not long-term. Larger, longer-term studies are needed before any conclusions can be drawn.

The safety, effectiveness and pharmacokinetics of VIRACEPT have not been evaluated in pediatric patients below the age of 2 years. While the results of this study are encouraging, larger studies are needed to explore the potential for this regimen to prevent maternal transmission. VIRACEPT currently should be used during pregnancy only upon consultation with a physician.

Study Published Showing VIRACEPT Benefit in Young Children

Results of another study, the Pediatric AIDS Clinical Trials Group 382 study of VIRACEPT in children, were published in the 16 December, 1999 issue of the New England Journal of Medicine. A total of 57 children with a mean age of 9 years were enrolled into PACTG 382; nearly all (96%) had previously received therapy with NAs, but none had prior experience with protease inhibitors or non-nucleoside reverse transcriptase inhibitors.

The trial found that the children receiving VIRACEPT plus efavirenz and one or more NAs experienced a rapid decline in HIV viral load, with a median decrease at 48 weeks estimated to be at least 2.7 log10 copies/mL. At 48 weeks, 81% of children with data available showed suppression of HIV viral load to levels below quantification (less than 400 copies/mL) - this corresponds to 61% of the children showing HIV suppression below the detection limit using a stringent intent-to-treat analysis.

Reanalyzing these results using an ultrasensitive viral load assay, 70% of children had HIV viral load below 50 copies/mL (53% using an intent-to-treat analysis). The CD4 cell count also increased significantly during the 48 weeks of treatment (p=<0.001), with a median increase of 74 cells/mm3 recorded at 48 weeks.

Median baseline values for CD4 cell count and viral load were 699 cells/mm3 and 4.0 log10 copies/mL, respectively. Children were treated with VIRACEPT 20-30 mg/kg three times daily in combination with efavirenz (mean dose 12 mg/kg once daily) and one or more nucleoside analogs. Dosages of both VIRACEPT and efavirenz were adjusted based on the actual concentrations of the drugs in the blood that were achieved.

Treatment with VIRACEPT plus efavirenz and one or more NAs was considered to be well-tolerated.