Selected Highlights from the 7th CROI: Studies of Switching Therapy
Several studies examined the effects on fat redistribution and metabolic changes after switching from a PI-based HAART combination to one without a PI. Overall, the results were mixed, with some possible trends towards some improvements in certain studies. Longer follow-up will be necessary to derive any definitive conclusions.
Andrew Carr, M.D., of St. Vincent's Hospital in Sydney reported the results of a randomized trial of 80 subjects in which the PI in participants' regimens was switched. All participants had significant experience with anti-HIV therapy, an undetectable plasma HIV (limit of detection 400 copies/mL), and fat redistribution. The NRTIs were maintained, the PI was stopped, and the following four drugs were added: abacavir, nevirapine, adefovir dipivoxil, and hydroxyurea (Hydrea). (Adefovir is an experimental nucleotide reverse transcriptase inhibitor.)
The results after 24 weeks were as follows: viral loads remained undetectable, high blood cholesterol and triglycerides improved rapidly, there was a gradual reduction in abdominal fat accumulation ("paunch"), and there was some reduction in the need for diabetic (high blood sugar) therapy. However, insulin resistance (a prediabetic state) did not change overall. Fat loss in the face and limbs did not improve and even worsened slightly. The investigators hypothesized that this may have been an effect of some of the maintained or new anti-HIV drugs. Both hydroxyurea and adefovir were associated with gastrointestinal symptoms that may have contributed to weight loss.
Switching to Abacavir, Nevirapine, or EfavirenzThe results of other studies indicated that switching from a PI to abacavir had relatively little effect on fat redistribution after 3-10 months in four studies (three were randomized). Two of the studies, however, revealed a trend towards fewer new symptoms of fat redistribution that was reported by study participants when compared with control subjects who remained on their PI-based regimen. These two studies included 245 subjects.
In yet another study, half of 104 persons randomized to switch to nevirapine had partial reversal in fat redistribution six months after switching. The abstract did not indicate whether this was by body imaging or measurements, self-reporting, or physician assessment. One of the four studies reported a significant decrease in blood cholesterol, another reported a significant decrease in blood triglycerides, with all other lipid results having either no statistical analysis or no significant change. In general, almost all subjects in these studies maintained an undetectable HIV RNA viral load, although a few subjects randomized to continue their PI regimen experienced viral rebound.
In another randomized study, Lidia Ruiz, Ph.D., and colleagues from the Lipodystrophy Study Group in Barcelona reported their results of a "switch" study. One hundred and six subjects with an undetectable viral load (limit of detection 400 copies/mL) and fat redistribution were switched from a PI/NRTI-based regimen to nevirapine/d4T/ddI. After 12 months, the results were stable, undetectable viral loads and mild improvements of high blood cholesterol and triglycerides. Dr. Ruiz also measured marginal increases in limb fat (in arms and legs) after nine months.
In four different nonrandomized studies, 135 subjects switched the PI in their regimen to efavirenz, with follow-up of 6-10 months. In one study by E. Martinez, M.D., and colleagues from University Hospital Clinic in Barcelona, 55% of 20 persons reported a decreased waistline. There was a trend towards confirmation by measurements of waist-to-hip ratios (WHR). In another study by P. Viciana, M.D., and colleagues from University Hospital in Seville, Spain, 67% of 39 subjects reported improvements that were not confirmed by WHR measurements.
There were two other studies authored by S. Gharakhanian, M.D., of Rothschild Hospital in Paris and E. Bonnet, M.D., of Pupan Hospital in Toulouse, France, respectively. There were no significant changes in body fat redistribution when measured by dual energy X-ray absorptiometry (DEXA) in 43 subjects (one study) or by observation in 33 subjects from the other study. There were no increases in cholesterol in three of the four studies, while one revealed an increase in the HDL cholesterol. (This finding has been reported with efavirenz in the past.) In three of these four studies, there was an increase in triglycerides, with one having statistical significance. Three of these studies found that viral loads remained undetectable in virtually all subjects (the fourth study did not report viral load data.) In the two studies that reported CD4 cell counts after the switch, CD4 cell levels remained the same in one and increased in the other.
WomenA cesarean ("C") section to help prevent HIV transmission to the unborn infant is associated with a 6-fold increase in maternal complications and a 120-fold increase in the need for the newborn to require a "breathing machine" (tube in the windpipe). Mary Jo O'Sullivan, M.D., of the University of Miami, FL, presented the information during her lecture entitled Management of the HIV-Infected Pregnant Woman.
HAART significantly alters the progression of cervical dysplasia, which is very common among HIV positive women, according to Howard Minkoff, M.D. Women taking HAART had a 66% reduction of cervical dysplasia progression and were 40% more likely to show regression (improvement) of dysplasia, when compared with those who were not receiving HAART. Cervical dysplasia is a precancerous condition primarily caused by human papillomavirus (HPV).
Forty-four percent of deaths among 885 women with HIV/AIDS were due to causes unrelated to HIV, according to Dr. D.K. Smith of the Centers for Disease Control and Prevention (CDC). Causes of death in the 44% included drug overdose, hepatitis, and sepsis/endocarditis (infection of the blood and inner heart lining). Women were from the HIV Epidemiology Research Study (HERS). The analysis included information gathered between April 1993 and December 1998.
This article was provided by San Francisco AIDS Foundation. It is a part of the publication Bulletin of Experimental Treatments for AIDS. Visit San Francisco AIDS Foundation's Web site to find out more about their activities, publications and services.