- Email: [email protected]
French AIDS experts say HAART break won't hurt
NEWS Brain changes predict decline in Alzheimer’s disease
C
changes with the clinical status of changes start in the entorhinal cortex, patients. work their way down De Leon’s team into the hippocampus, studied four groups of and ultimately spread patients for 3 years. to the neocortex. The Eight patients started sequence gives us a out with normal cognihandle on how far tive processes and along somebody is [in stayed normal; eight the disease process], went from being norand allows us to premal to having MCI; dict future change”, six had MCI throughsays de Leon. out the study; and six De Leon and cowent from MCI to workers previously End of a disease pathway? Alzheimer’s disease. showed that MRI Patients who remained stable had could yield a good approxiMaternal cells and autoimmunity no longitudinal alterations in the mation to the true volume Two-way trafficking of cells between mother and entorhinal cortex, but those who of the entorhinal cortex, a fetus can lead to engraftment and persistence declined had significant alterations, brain region that is hard to of maternal cells in children, as well as of fetal which in turn predicted the developmeasure with older imaging cells in the mother, J Lee Nelson (University of ment of hippocampal atrophy. methods (Lancet 1999; 353: Washington, Seattle, WA, USA) reported at “Degeneration seems to start in 38–39). Other studies had EB’99. Microchimerism—the presence in the one place and then spread. By the suggested that the entorhinal body of low numbers of another individual’s time the hippocampus is involved, cortex and hippocampus may cells—was first proposed by Nelson as a that’s really the MCI stage. Neobe involved in Alzheimer’s mechanism for scleroderma development cortex involvement is essential for disease before the neocortex, (Lancet 1998; 351: 559–62). Now, Nelson and symptoms of dementia”, explains de and that “massive losses” of co-workers, report that microchimerism could Leon. Physiological and metabolic entorhinal neurons occurred also be involved in primary biliary cirrhosis and studies are underway to find out what even in very mild cognitive systemic lupus. “These [foreign] cells could be changes are associated with the strucimpairment (MCI). These specifically targeted for treatment with tural changes, he adds. “We want to findings, says de Leon, monoclonal antibodies, instead of using agents know what is driving these patients “created an opportunity for which are globally reactive on the immune forward in disease time.” us to catch a glimpse” of system”, suggests Nelson. brain changes over time, and to correlate these Marilynn Larkin
hanges in the brain’s anatomy, detectable by use of magnetic resonance imaging (MRI), precede and predict the progressive memory impairment seen in Alzheimer’s disease, say researchers from New York University (New York, NY, USA). “We now have a view of the time course of events that occur in the [degenerating] brain”, says Mony de Leon, who reported the team’s findings at the annual meeting of the Federation of American Societies for Experimental Biology (EB’99; Washington DC; April 17–21). “The
French AIDS experts say HAART break won’t hurt
I
f highly active antiretroviral therapy (HAART) for HIV-1 infection is interrupted, patients experience a rapid rebound in viral load to pre-HAART values. But, say French clinicians, a 1-month interruption may not have a deleterious effect on therapy once it is restarted. HIV-1-positive people often need short breaks from HAART because of drug intolerance, surgery, or other reasons, but the effects of such interruptions on viral load and efficacy of subsequent treatment are unknown. Christine Katlama (Hôpital Pitié-Salpêtrière [HPS], Paris, France) and her team
THE LANCET • Vol 353 • April 24, 1999
hypothesised that “if a successful therapy is completely and abruptly interrupted then no drug-selection would be applied on the virus”. To test this, the team treated ten antiretroviral-naive patients with zidovudine, lamivudine, and indinavir for 28 days, then monitored them while therapy was stopped for 28 days then restarted. Viral loads started to rise within a week of stopping HAART, and had increased to 96% of preHAART values by 28 days. But, “no resistance-conferring mutations were observed”, and reintroduction of HAART resulted in a viral-load decline similar to that after initial
treatment. Viral load was “maintained below 200 copies/mL in all patients who continued triple therapy for 4 months or more”, write the authors ( AIDS 1999; 13: 677–83). Roland Tubiana (HPS), a lead author, stresses that “the study does not show that you should interrupt therapy . . . it only shows that you can if you have to”. But, “if effective therapy is interrupted after, say, 3 years, you might lose 3 years of immune reconstitution”. More studies are needed to decide whether intermittent therapy will be routinely possible, he adds. Kelly Morris
1417
C
changes with the clinical status of changes start in the entorhinal cortex, patients. work their way down De Leon’s team into the hippocampus, studied four groups of and ultimately spread patients for 3 years. to the neocortex. The Eight patients started sequence gives us a out with normal cognihandle on how far tive processes and along somebody is [in stayed normal; eight the disease process], went from being norand allows us to premal to having MCI; dict future change”, six had MCI throughsays de Leon. out the study; and six De Leon and cowent from MCI to workers previously End of a disease pathway? Alzheimer’s disease. showed that MRI Patients who remained stable had could yield a good approxiMaternal cells and autoimmunity no longitudinal alterations in the mation to the true volume Two-way trafficking of cells between mother and entorhinal cortex, but those who of the entorhinal cortex, a fetus can lead to engraftment and persistence declined had significant alterations, brain region that is hard to of maternal cells in children, as well as of fetal which in turn predicted the developmeasure with older imaging cells in the mother, J Lee Nelson (University of ment of hippocampal atrophy. methods (Lancet 1999; 353: Washington, Seattle, WA, USA) reported at “Degeneration seems to start in 38–39). Other studies had EB’99. Microchimerism—the presence in the one place and then spread. By the suggested that the entorhinal body of low numbers of another individual’s time the hippocampus is involved, cortex and hippocampus may cells—was first proposed by Nelson as a that’s really the MCI stage. Neobe involved in Alzheimer’s mechanism for scleroderma development cortex involvement is essential for disease before the neocortex, (Lancet 1998; 351: 559–62). Now, Nelson and symptoms of dementia”, explains de and that “massive losses” of co-workers, report that microchimerism could Leon. Physiological and metabolic entorhinal neurons occurred also be involved in primary biliary cirrhosis and studies are underway to find out what even in very mild cognitive systemic lupus. “These [foreign] cells could be changes are associated with the strucimpairment (MCI). These specifically targeted for treatment with tural changes, he adds. “We want to findings, says de Leon, monoclonal antibodies, instead of using agents know what is driving these patients “created an opportunity for which are globally reactive on the immune forward in disease time.” us to catch a glimpse” of system”, suggests Nelson. brain changes over time, and to correlate these Marilynn Larkin
hanges in the brain’s anatomy, detectable by use of magnetic resonance imaging (MRI), precede and predict the progressive memory impairment seen in Alzheimer’s disease, say researchers from New York University (New York, NY, USA). “We now have a view of the time course of events that occur in the [degenerating] brain”, says Mony de Leon, who reported the team’s findings at the annual meeting of the Federation of American Societies for Experimental Biology (EB’99; Washington DC; April 17–21). “The
French AIDS experts say HAART break won’t hurt
I
f highly active antiretroviral therapy (HAART) for HIV-1 infection is interrupted, patients experience a rapid rebound in viral load to pre-HAART values. But, say French clinicians, a 1-month interruption may not have a deleterious effect on therapy once it is restarted. HIV-1-positive people often need short breaks from HAART because of drug intolerance, surgery, or other reasons, but the effects of such interruptions on viral load and efficacy of subsequent treatment are unknown. Christine Katlama (Hôpital Pitié-Salpêtrière [HPS], Paris, France) and her team
THE LANCET • Vol 353 • April 24, 1999
hypothesised that “if a successful therapy is completely and abruptly interrupted then no drug-selection would be applied on the virus”. To test this, the team treated ten antiretroviral-naive patients with zidovudine, lamivudine, and indinavir for 28 days, then monitored them while therapy was stopped for 28 days then restarted. Viral loads started to rise within a week of stopping HAART, and had increased to 96% of preHAART values by 28 days. But, “no resistance-conferring mutations were observed”, and reintroduction of HAART resulted in a viral-load decline similar to that after initial
treatment. Viral load was “maintained below 200 copies/mL in all patients who continued triple therapy for 4 months or more”, write the authors ( AIDS 1999; 13: 677–83). Roland Tubiana (HPS), a lead author, stresses that “the study does not show that you should interrupt therapy . . . it only shows that you can if you have to”. But, “if effective therapy is interrupted after, say, 3 years, you might lose 3 years of immune reconstitution”. More studies are needed to decide whether intermittent therapy will be routinely possible, he adds. Kelly Morris
1417