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Family Health and Relationships Newsletter
December 17, 2007


In This Issue
• Overlooked Mutation Can Spur HIV Drug Resistance
• Lack of Sleep Tied to Weight Gain in New Moms
• Fetal Surgery Saves Baby After Early 'Water Break'
• Lupus Treatment Linked to Male Fertility Problems
 

Overlooked Mutation Can Spur HIV Drug Resistance


SATURDAY, Dec. 1 (HealthDay News) -- One in 10 HIV-infected people receiving drug treatment harbors a hidden genetic mutation that renders certain strains of the virus more resistant to antiretroviral medications, researchers say.

Their study suggests that the N348I mutation should now be added to standard HIV gene tests that AIDS specialists use as they decide which cocktail of drugs a patient should receive.

"The importance of N348I is also underscored by the fact that it appears relatively early after starting drug therapy," noted study senior author Gilda Tachedjian, head of the Molecular Interactions Group at the Macfarlane Burnet Institute for Medical Research and Public Health, in Melbourne, Australia.

The mutation, largely overlooked by researchers, appears to confer resistance to zidovudine (AZT or Retrovir), the first drug ever approved to fight HIV; and nevirapine (Viramune), one of a group of powerful antiretroviral medications.

Both medicines fall into a broad category of drugs called reverse transcriptase inhibitors (RTIs), so named because they target a key enzyme on HIV called reverse transcriptase.

Tachedjian's group published its findings late Friday in the December issue of PLoS Medicine on the eve of World AIDS Day.

Gene tests aimed at gauging a particular strain of HIV's resistance to common AIDS drugs are routine in clinical practice, noted Mattias Gotte, an associate professor of microbiology and immunology at McGill University in Montreal. Gotte is also the author of an accompanying commentary in the journal.

"You go as an infected person to a clinician, and you get a certain regimen. Most of the time the clinician uses genotyping [gene tests] to see whether certain preexisting mutations may compromise therapy," he explained. "The other thing that happens is when you are on a failing regimen. Then, the clinician would genotype the virus and eventually base his or her decision on the results."

The trick is to match the patient's version of HIV to a group of drugs that will be least prone to resistance.

In the case of nevirapine and other widely used RTIs, AIDS experts thought they knew where the key points of resistance lay on the reverse transcriptase molecule, and so they designed their tests accordingly.

"Genotyping assays currently look for drug-resistance mutations in the first two-thirds (N-terminal region) of the reverse transcriptase," Tachedjian explained. "The reason for this is that it is where most of the important resistance mutations have occurred."

But there's another region on the enzyme, called the C-terminal, that's also essential to proper reverse transcriptase function.

"Our logic for the current study was that since the C-terminal region is involved in how the enzyme 'works,' then it is likely that drug resistance mutations could [also] emerge in this region," Tachedjian said.

In their study, her team analyzed samples from more than 1,000 HIV patients who had received antiretroviral drug therapy. They then compared their results to samples taken from 368 HIV-positive patients who had not yet undergone drug therapy.

The C-Terminal N348I mutation turned up in 12 percent of patients who'd been exposed to HIV-suppressing drugs, the researchers report.

In contrast, fewer than 1 percent of the not-treated patients had the resistance-linked mutation -- suggesting that it developed after the virus had been exposed to AIDS drugs.

"The N348I mutation is different from most of the other mutations described to date because it confers some level of resistance to nevirapine and zidovudine, which are drugs belonging to two different classes of reverse transcriptase inhibitors," Tachedjian pointed out. "N348I can work alone to confer resistance to nevirapine and zidovudine and can augment resistance when in the presence of other drug mutations found in the N-terminal region of the enzyme."

The trouble is, standard genotyping tests are designed to pick up N-terminal mutations but they ignore the C-terminal region, including N348I.

According to Tachedjian, that means the finding "may have implications for genotypic resistance testing, particularly for patients on zidovudine and nevirapine therapy, and therefore should be considered for incorporation in [standard] genotyping assays."

The advent of new antiretroviral drugs means these gene tests are already going to have to be altered, she added, "and while we are making these changes it could be relatively straightforward to include" the C-terminal region, and N348I, in the tests as well.

Tachedjian believes other overlooked, resistance-conferring mutations might also be hiding out in the C-terminal region, and her team is currently looking into that possibility.

In the meantime, the N348I discovery could have implications for AIDS drug development, Gotte pointed out.

"We learn a lot when we study mechanisms of resistance, in terms of what we should avoid in regard to drug development and how we can make drugs better," he said.

Gotte stressed that HIV-positive patients should not be overly concerned that their doctors are missing a key factor as they seek to determine the best treatment strategy.

While adding N348I to the genotyping mix will improve treatment design, "it's still a minor piece of the puzzle that's missing here," he said. "I wouldn't be too worried about this because clinicians also look for other parameters" as they choose effective therapies, he added.

More information

Find out more about HIV at the U.S. National Institute of Allergy and Infectious Diseases.


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Lack of Sleep Tied to Weight Gain in New Moms


WEDNESDAY, Nov. 28 (HealthDay News) -- If your new baby is keeping you awake at night, take note: A first-of-its-kind study suggests that sleep deprivation after giving birth may limit a new mother's ability to shed those pregnancy-related pounds.

It's not clear why there may be a link between sleep loss and lack of weight loss. Still, the possibility of a connection is intriguing, said study lead author Erica P. Gunderson, an investigator with the Kaiser Permanente Division of Research in Oakland, Calif.

"Getting enough sleep may be as important as a healthy diet and physical activity to returning to pre-pregnancy weight," Gunderson said.

According to the study authors, scientists have linked low amounts of sleep to obesity, heart disease and diabetes. But there's been little research into the connection between sleep and pregnancy and weight.

For the new study, the researchers looked at the weights and sleep patterns of 940 women who enrolled in a study in Massachusetts during early pregnancy from 1999 to 2002.

A year after giving birth, 124 of the women retained at least 11 pounds of the weight they had gained during pregnancy. After the researchers adjusted the statistics to take into account such factors as family income, they found that women who slept five hours a day six months after giving birth were more than three times likelier to keep weight on compared to women who slept seven hours.

Sleeping six, seven or eight hours a day didn't appear to raise a woman's risk of keeping on weight. "Basically, the women who were sleeping fewer hours did not lose as much weight as women who slept several more hours," Gunderson said.

The study findings, by researchers at Kaiser Permanente and Harvard Medical School/Harvard Pilgrim Health Care, were published in the November issue of the American Journal of Epidemiology.

It might seem that people who sleep less would actually lose more weight, because they'd spend more time burning calories while awake. But the study suggests the opposite, Gunderson said, perhaps because people become hungrier due to lack of sleep.

Also, she added, "If you're awake more, you may have more opportunities to eat."

Claire D. Brindis, a professor of pediatrics at the University of California, San Francisco, said her own experience of giving birth to two children taught her about how stress, sleep and weight are all connected.

"Having lived this, it's partly that you're more tired, and you feel you need food to keep you energized," she said. "And when you're stressed, you feel like you can reward yourself with food. It creates a sense of comfort."

Gunderson said the next step is to understand what women who sleep less after pregnancy have in common. Doctors can then "target women who may not be getting enough sleep and find ways to support them," she said.

More information

To learn more about sleep, visit the National Sleep Foundation  External Links Disclaimer Logo.


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Fetal Surgery Saves Baby After Early 'Water Break'


MONDAY, Oct. 29 (HealthDay News) -- A first-of-a-kind surgery in the womb saved the life of an unborn baby after premature rupture of the fetal membranes ("water breaks"), German doctors report.

When the mother's fetal membranes burst during the 20th week of pregnancy, the unborn child's chances of surviving birth were slim, said doctors at the Bonn University Clinic in Germany. Not only was there a high risk of infection, the baby's lungs stopped growing, and she most likely would have suffocated after birth.

In an effort to save the unborn child, the doctors performed surgery in the womb to stimulate lung growth. They inserted a ballpoint pen-sized fetoscope through a small opening in the mother' stomach and, guided by a camera and ultrasound, moved the device into the mouth and trachea of the unborn baby.

The doctors then inflated a miniature balloon that blocked the respiratory channel in order to prevent drainage of fluid produced by the prenatal lung. The resulting build up of fluid pressure stimulated lung growth.

The baby girl, who was born in the 33rd week of pregnancy, is now a year old and in good health.

"The prenatal operation only takes one or two hours. Competent follow-up care of the children after birth is at least as important for their healthy survival," Thomas Kohl, head of the German Center of Fetal Surgery & Minimally Invasive Therapy at Bonn University Clinic, said in a prepared statement.

The doctors described the procedure in an article published Oct. 29 in the journal Fetal Diagnosis and Therapy.

More information

The American Academy of Family Physicians has more about premature rupture of fetal membranes  External Links Disclaimer Logo.


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Lupus Treatment Linked to Male Fertility Problems


THURSDAY, June 28 (HealthDay News) -- Sperm abnormalities in men with lupus may be linked to intravenous treatment with the immunosuppressant cyclophosphamide (IV CYC), according to Brazilian researchers.

In a new study, published in the July issue of Arthritis & Rheumatism, researchers studied 25 men with systemic lupus erythematosus (SLE) and 35 healthy controls.

SLE is an autoimmune disease that mainly affects women in their reproductive years but can also affect men. There have been concerns about the future fertility of men with SLE, but, until now, no studies have been conducted on testes function and sperm abnormalities in men with SLE.

The researchers examined the genitalia and analyzed the semen of all of the participants.

They found that the men with SLE had lower testicular volume, a lower sperm count, lower sperm motility, lower sperm volume and a lower percentage of normally formed sperm, compared with their healthy counterparts.

Furthermore, the SLE patients with more severe sperm abnormalities had a higher frequency of treatment with IV CYC, suggesting that IV CYC treatment may be associated with fertility-compromising damage to the testes.

The researchers pointed out that although it is not possible to predict which men with SLE will become infertile, it is important to discuss the option of freezing and storing sperm with all male SLE patients early in the course of the disease.

More information

The Lupus Foundation of America has more about lupus in men  External Links Disclaimer Logo.


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