New Strain of H.I.V.

European scientists have discovered a new strain of the virus that causes AIDS and linked it to gorillas, creating a mystery about when and how the first patient found to have the strain became infected.

It is thought to be likely that this is the first time scientists have documented the jump of a simian immunodeficiency virus to humans from a gorilla. All three other known strains of the human immunodeficiency virus, H.I.V.-1, have been linked to chimpanzees. But genetic tests showed that the new virus was closely related to a recently recognized gorilla virus.

The most likely explanation for the new virus’s emergence is gorilla-to-human transmission, probably a result of humans slaughtering apes or handling or eating their meat.

But the scientists said they could not dismiss the possibility that the chimpanzee virus linked to H.I.V.-1 was transmitted to gorillas and then to humans, or was directly transmitted to humans and then to gorillas.

The new virus strain was isolated in 2004 from a 62-year-old woman upon her arrival in Paris from Cameroon in West Africa. She has not been treated for AIDS and has no signs of the syndrome, the scientists said.

The woman had lost weight in 2003 and had been ill with a fever a number of times, the scientists said in reporting the discovery, in the Aug. 2 issue of the journal Nature Medicine.

Her husband died in 1984 from complications of a stroke. It is not known if he was infected with H.I.V. The woman had six children, all born before 1980, a year before doctors first recognized AIDS; two of the children died of noninfectious causes, and none of the surviving children have H.I.V.

The authors of the report said they presumed that she had been infected through sex. The woman told her doctors that she had sexual partners in Cameroon after her husband’s death, but there was no information about whether any were infected — or, if they were, how they had contracted the virus.

The new virus may escape detection by standard blood and laboratory tests for H.I.V.-1. New testing methods developed in recent years have allowed scientists to detect subtypes of H.I.V.-1. The three others are known as H.I.V.-1 Groups M, N and O. Dr. Plantier’s team calls the new one H.I.V.-1 Group P.

Protein Excreted In Urine May Be Help In Diagnosing Kidney Disease Caused By HIV

New data collected at Columbia University Medical Center and by the Mount Sinai School of Medicine are helping researchers understand the extent to which a certain protein – NGAL – can play a significant role in marking chronic kidney disease resulting from HIV while at the same time distinguishing nephropathy from more common causes such as diabetes and hypertension.

It's well-known that Human Immunodeficiency Virus-associated nephropathy (HIVAN) is an important cause of kidney disease in HIV-infected patients. Antiretroviral therapy plays an important role in the treatment of HIVAN, yet despite advances in understanding HIVAN, current recommendations for treatment have largely been based on observational data and can only definitively made after a kidney biopsy.

The current study, spearheaded by Columbia University's Jonathan Barasch, M.D., Ph.D., along with Ali Gharavi M.D., Ph.D., Neal Paragas M.S., Thomas Nickolas M.D., M.S., and Vivette D'Agati M.D., together with Paul Klotman, M.D., Christina Wyatt M.D., and Susan Morgello M.D., of the Mount Sinai School of Medicine and Landino Allegri in Parma, Italy, and Prasad Devarajan in Cincinnati Childrens Hospital, represents the examination of data from human cohorts in New York and Parma, and from mouse models created by Dr. Klotman.

The team noted that NGAL, or Neutrophil Gelatinase Associated Lipocalin, a protein they previously discovered in damaged kidneys, was prominently expressed in kidney tissue and in the urine of humans and in mouse models of HIVAN. The high levels of the urine protein were out of proportion to the degree of chronic renal failure, for example that typifies patients with other types of chronic glomerular diseases of both mice and humans. Most strikingly, Paragas, Barasch, and Gharavi noticed that the rise in urinary NGAL levels was in conjunction with the development of a specific type of lesion, namely tubular cysts that typify HIVAN. The association with these cysts consequently may justify their biopsy or an aggressive treatment with antiretroviral drugs when high levels of urine NGAL are discovered.

"From what we can tell, NGAL is unexpectedly expressed in great abundance by kidney cysts allowing the clinician to potentially identify HIVAN among other types of chronic kidney diseases and hopefully to intervene to prevent a kidney from ultimately dying from what physicians refer to as ESRD, or 'end-stage renal disease,'" Dr. Barasch says.

Dr. Barasch cautions that studying a much larger human cohort would be needed in order to determine the precise relationship of NGAL to HIVAN and whether the protein is a good enough predictor of tubular cysts, but he finds the results of the study unexpected and intriguing.

The research appears in an upcoming Journal of the American Society of Nephrology and was funded in part by the Emerald Foundation, the March of Dimes, the National Institutes of Health and the Glomerular Center of Columbia University.

Not adequately diagnosing kidney problems can be life-threatening and NGAL expression which is induced in kidney disease and damage can help identify patients at risk of kidney failure even in those without HIV. Last year, Dr. Barasch and Nickolas found that approximately 65 percent of patients with NGAL protein in the urine upon presentation to the Emergency Department will require care by a nephrologist, another 32 percent will need dialysis, and 29 percent will require care in the intensive care unit, over the course of a week following the subsequent hospitalization. That study was published in the June 3, 2008, issue of the Annals of Internal Medicine.

Earlier HIV Antiviral Treatment Can Be Cost Effective In Areas Of Limited Resources, South African Study Finds

Early initiation of lifesaving antiretroviral therapies should be the standard of care for all HIV-infected patients, even those in countries with limited medical and financial resources, according to a study led by researchers at Massachusetts General Hospital (MGH) and the Desmond Tutu HIV Centre, University of Cape Town, South Africa.

The team reports in the August 4 Annals of Internal Medicine that starting antiretroviral therapy (ART) when the level of CD4 T cells drops below a threshold of 350 per microliter of blood, compared with below 250, would prevent nearly 76,000 deaths and avert 66,000 opportunistic infections over the next five years at an estimated cost of $1,200 per year of life saved. The study's publication coincides with the International AIDS Society Conference meeting which started yesterday in Cape Town.

The study provides strong support for broadening the eligibility standards for ART in settings with sufficient access to drugs, the authors note. In the U.S. and other developed countries, ART is usually initiated when the CD4 count – a measure of immune system function – drops below 350. Recognizing that ART is both costly and can have significant side effects, the 2006 World Health Organization (WHO) treatment guidelines suggest waiting until CD4 counts drop below 200 or until patients develop AIDS-related complications.

"While those standards accommodate the limited resources and short supply of medications in many settings, the greater prevalence of tuberculosis and other opportunistic infections in places like South Africa argue for earlier treatment initiation, even before the results of ongoing clinical trials are known." says Rochelle Walensky, MD, MPH, of the MGH Division of Infectious Disease, associate professor of Medicine at Harvard Medical School, who led the study.

Definitive clinical trial findings will not be available for several years. Yet in countries like South Africa, which currently has the world's highest burden of HIV infection, information is needed today to guide treatment policies and practices. To address this need, Walensky and colleagues developed a mathematical model to simulate HIV treatment and its associated health and economic outcomes. The model calculated the additional costs of earlier treatment, its potential toxicities and its benefits, including TB prevention. It also calculated how much delaying ART would shorten patients lives and then estimated the cost per extra year of life gained – a standard measure of cost-effectiveness – of earlier ART initiation.

"The time has come to act on the information we now have, nearly all of which supports starting treatment earlier. We can re-evaluate the situation after the trials, but until those results are available, the evidence points to saving lives with earlier treatment," says co-author, Robin Wood, FCP, MMed, DTM&H, director of the Desmond Tutu HIV Centre at the Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, a leading HIV clinical research group in South Africa

Additional co-authors of the Annals of Internal Medicine report are Lindsey Wolf, Mariam Fofana, and Kenneth Freedberg, MD, MSc, MGH; Elena Losina, PhD, Brigham and Women's Hospital; Neil Martinson, MBBCh, MPH, WITS Health Consortium, Johannesburg, South Africa; A. David Paltiel, PhD, Yale University; Xavier Anglaret, MD, PhD, University of Bordeaux, France; and Milton Weinstein, PhD, Harvard School of Public Health. The study was supported by grants from the National Institute for Allergy and Infections Diseases and the Doris Duke Charitable Foundation.