Treatment Issues: Newsletter of Experimental AIDS Therapies - Volume 17, Number 9, September 2003
Bob Huff

At the 43rd Annual ICAAC Conference in Chicago, Joseph Gathe, a clinical investigator and HIV clinician at a large inner city clinic in Houston, Texas, presented a poster reporting 24-week results from a controversial pilot study that employed only one antiretroviral to treat HIV-infected patients starting their first regimen. The 30 patients in the study were treated with the twice-a-day protease inhibitor Kaletra, a co-formulation of lopinavir with low-dose ritonavir added for pharmacokinetic enhancement. At week 24 of the 48-week study, the one-drug strategy had produced virologic efficacy comparable to that seen with standard triple-drug HAART.

The study group contained a large proportion of individuals with advanced HIV disease, with 54% having both a CD4 count below 50 and viral load above 100,000. Overall the group had a mean viral load of 260,000 copies/mL and a mean CD4 cell count of 170. Persons with active, life-threatening AIDS were excluded. Nearly all of the subjects were male; 60% were white, 20% black and 20% Hispanic. Kaletra dosing was adjusted by weight, with patients weighing less than 70kg receiving 3 capsules twice-a-day and those over 70kg receiving 4 capsules. Viral load and CD4 cell counts were monitored during usual patient visits to the Ryan White funded free clinic. No pharmaceutical support or other outside funding was available to the study.

By week 24 of the 48-week study, 8 of the 30 participants had left, with 2 lost to follow-up, 2 withdrawing due to GI intolerance, 1 due to active hepatitis B infection and 1 because of non-adherence. One patient was deported. Another patient was excluded because of virologic failure, although the details of this case were not reported.

Of the 22 patients who remained on treatment, 21 (95%) achieved virologic response defined as viral load less than 400 copies at week 24. Using an intent-to-treat analysis, with 21 of 30 patients achieving viral load below 400 copies, the 24-week response rate was 70%. The mean reduction in viral load for those remaining on the study to week 24 was ­2.57 log copies/mL. The average CD4 count had increased by 219 cells at week 24. No significant toxicity was seen and no genotypic or phenotypic resistance mutations were detected.

A single patient remaining on the study failed to achieve viral suppression below 400 copies and added saquinavir to his regimen at week 32. The failing individual’s baseline viral load was 500,000 and had declined to about 1500 at week 24 then rose to just under 5,000 at the time of treatment intensification.

Dr. Gathe pointed to results from a dose-finding trial that administered lopinavir/ritonavir alone to 32 patients for 3 weeks before adding NRTIs. By week 3, the mean viral load decrease was -1.85 log copies/mL. At week 2, the mean decline in viral load in patients receiving monotherapy was similar to that of those on a 3-drug combination (-1.73 vs. -1.68 log copies/mL). (Murphy RL, et al. AIDS. 2001 Jan 5;15(1):F1-9)

He also cited a 48-week trial of Kaletra that reported finding no genotypic or phenotypic resistance in subjects experiencing virological failure. This suggested that, in the event viral suppression could not be maintained with single drug Kaletra, subsequent susceptibility to intensification would likely not be in jeopardy. (Walmsley S, et al. N Engl J Med. 2002 Jun 27;346(26):2039-46)

Triple combination therapy produced welcome and dramatic benefits for patients when it was widely introduced in 1995. Since then, the idea of “monotherapy” has become synonymous with an era of inadequate treatment options and a high death rate from AIDS. Increasingly, however, economic pressures are stimulating research into strategies that may possibly conserve scarce resources without compromising outcomes. Dr. Gathe will continue this study to 48 weeks and is preparing a follow-up study of single-drug HAART that will begin enrolling later this year.

Gathe JC, et al. Pilot study of the safety and efficacy of Kaletra (LPV/r) as single drug HAART in HIV+ ARV naive patients. Interim analysis of subjects completing at least 24 weeks of a 48 week study. 43rd ICAAC, Chicago, 2003. Poster 845.

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