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November 2001

The Newsline section recalls the pioneering HIV/AIDS publication of the same name produced by the People With AIDS Coalition of New York (PWAC-NY).


End-of-Life Discussions and Preferences Among Persons With HIV

Lack of advance planning leaves many patients, families and physicians unprepared for end-of-life care decisions. While the prognosis has improved for many persons with AIDS, a need for planning remains urgent. This study was undertaken to evaluate the prevalence of end-of-life discussions, use of advance directives, and preferences with respect to end-of-life care and their relationship with patient demographics, clinical status, psychosocial factors, and practitioner characteristics among HIV-infected persons. The study was a cross-sectional survey of a US probability sample using 2,864 participants representing 231,000 adults receiving care for HIV. It was conducted between January 1996 and April 1997. The main focuses of the survey were communication with physician on end-of-life issues, completion of an advance directive, preference for aggressiveness of care, and the willingness to tolerate future permanent adverse health states. Of the 2,864 patients surveyed, 1,432, or 50 percent, had discussed some aspect of end-of-life with their practitioner, and 1,083 (38 percent) had completed an advance directive. According to the authors, "Patients were more likely to complete an advance directive after a physician discussion." Overall, physicians discussed end-of-life care less with blacks and Latinos than with whites. Women and patients with children in the household had the highest rate of communication with a practitioner, with patients infected with HIV via injection drug use and those with less education having the least communication with practitioners about end-of-life issues.

In their discussion, the investigators emphasized that "Half of all persons infected with HIV are at risk of making end-of-life decisions without prior discussions with their health care practitioners. Blacks, Latinos, intravenous drug users, and less educated individuals need advance care planning interventions in clinical HIV programs." (Journal of the American Medical Association, 285; No 22: P 2880-2887, Neil S. Wenger, M.D. et al.)


Fewer Prisoners Dying of AIDS Despite Higher HIV Totals

AIDS-related deaths in prisons have fallen sharply because of better treatment, but increasing numbers of inmates have tested positive for HIV, according to a Justice Department study. In 1999, 242 state prisoners died from AIDS-related causes, down from a peak of 1,010 in 1995, the department's Bureau of Justice Statistics reported. Sixteen federal prisoners and 78 local inmates died from AIDS, the bureau said.

There were nearly 10,000 confirmed AIDS cases in federal, state and local correctional facilities in 1999: 6,200 in state prisons, 3,100 in local jails and 430 in federal institutions.

The overall inmate population was 1.9 million. From 1995 to 1999, the number of state and federal prisoners testing positive for HIV rose by 1,500, to nearly 25,800. New York held 7,000 HIV-positive state and federal inmates in 1999, more than any other state. The decline in deaths and the increase in the number of people with the virus occurred as the inmate population soared 19 percent from 1995 to 1999. The number of HIV-positive prisoners grew at a slower rate, 6 percent, than the overall prison population.

The study reported that with the introduction of different drugs and therapies, "there has been vast improvement in the effectiveness" of care. While prisoners "are getting better treatment than they were five years ago, to say that they are getting decent treatment is an overstatement," said Carlos Arboleda, director of treatment education at the National Minority AIDS Council. "If there is a lockdown, inmates may not have access to treatment," Arboleda said. "Security always supersedes treatment and that's the nature of prisons. I don't know if it's ever going to change." (New York Times, 07/09/01, Associated Press)


AIDS Drug Could Be Easier on the Heart

A preliminary study by Bristol-Myers Squibb suggests that a new AIDS drug may avoid the heart problems linked to many medications that are currently available. The study compared atazanavir, an experimental protease inhibitor, to an older drug in 467 HIV patients. Cholesterol and triglyceride counts increased only slightly or dropped among patients on the new drug, compared with increases higher than 16 percent for those on the older drug. Physicians have become increasingly concerned about increases in cholesterol and other blood chemicals linked to heart disease among people taking protease inhibitors. (USA Today, 07/10/01)


Studies Show Virus "Blips" Don't Necessarily Mean AIDS Drugs Aren't Working

Two studies published in the Journal of the American Medical Association (JAMA) suggest that the slight "blips" in HIV virus levels that many AIDS patients experience while taking drug cocktails do not necessarily mean the treatment is failing. Doctors generally try to suppress the AIDS virus to levels undetectable by routine tests. Up to now, doctors believed that when HIV rises back to detectable levels, it means that the virus is becoming drug-resistant and that the patient has to switch medications. "Unnecessary regimen switching may result in disruption of a patient's medication routine, toxic effects from new drugs, and premature discarding of useful drugs," according to one of the studies, led by Dr. Diane Havlir of the University of California-San Diego.

Patients in both studies received standard cocktails of AZT and 3TC plus protease inhibitors. Havlir and colleagues analyzed data on 241 patients followed for about 16 months and a group of 13 followed for about 4.5 years. "Intermittent viremia" -- occasional, detectable AIDS virus levels -- occurred in about 40 percent of the 241 patients and in six of the 13. Persistently high virus levels indicating the treatment failed occurred in 30 patients, but were no more likely to occur in those with virus blips (JAMA 2001; 286: 171-179).

In the other JAMA report, Dr. Deborah Persaud from Johns Hopkins University Children's Center and colleagues studied blood samples of 20 AIDS patients on standard drug treatment for at least two years. They found that standard treatment seemed to block virus mutation even in patients with intermittent blips of virus activity (JAMA 2001; 286: 196-207). Dr. Steven Deeks of the University of California-San Francisco's AIDS Program, who wrote an accompanying editorial, noted that the studies are only preliminary, and their findings apply mainly to patients whose cocktails include a protease inhibitor. (Associated Press, 07/11/01, Lindsey Tanner)


Interrupting AIDS Treatment Shows Promise

A controversial treatment in which HIV patients take medications only on alternate weeks appears to hold HIV at bay without creating a drug-resistant virus, according to researchers. "Our results seem to be an indication that small cyclical treatment interruption could be a feasible option," said Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases. More than a year after the treatment program began with 10 patients, Fauci said he has seen no evidence of the two most feared complications. During the one-week period in which patients went off the drugs, Fauci said no patient recorded an increase in viral levels.

Further, no drug-resistant mutation has appeared either, Fauci said at the conference.

Other structured treatment interruption (STI) programs have been tried, Fauci said, including two-months-on, one-month-off approach, but that strategy showed the ability of the virus to rebound above detectable levels. Now Fauci is focusing on the one-week-on, one-week-off regimen. "The short period of time off drugs does not appear to give the virus enough time to rebound," he said.

Georgetown University researcher Dr. Franco Lori said the immune systems of some STI patients may be able to recognize the virus and attack it when it rebounds. He warned, however, that when the virus rebounds it can destroy some key immune cells that are slowly regenerating. Scientists also expressed fears that patients might try their own forms of STI, with disastrous results. While he called Fauci's results interesting and impressive, Dr. Joseph Eron, associate professor of medicine at the University of North Carolina-Chapel Hill, noted that the study involved just 10 patients. Fauci said a larger trial of STI is being prepared. (United Press International, 07/10/01, Ed Susman)


Higher HIV Rates Among Gay Latino Men Who Face Racism

Gay Latino men who have been the target of racism and homophobia are more likely to engage in high risk sexual behavior and more likely to have HIV, according to a national survey by the National Gay and Lesbian Task Force.

Researcher Rafael Diaz of the Institute on Sexuality, Inequality and Health at San Francisco State University, which co-authored the study, said it "shows that HIV risk is embedded in the context of social inequality and oppression that these men experience in their life." Men who had positive gay role models were less likely to contract HIV, Diaz said.

The survey included 912 gay Latino men in Los Angeles, Miami and New York. The study divided the men into two groups: those who had unprotected sex and multiple partners; and those who were monogamous and had protected sex. Seventy-three percent of men in the high-risk group reported experiences with racial and anti-homosexual bias, compared to 62 percent in the low-risk group. Those men who engaged in low-risk sexual behavior "saw that if you are gay, you can be successful and a productive member of society," Diaz said. "Having exposure to that made them less at risk, and at least having one person in your family that you were able to talk to openly about your homosexuality helped."

Nearly 40 percent of HIV cases reported in Los Angeles County last year were among Latino men, compared with 14 percent in 1985. (Associated Press, 07/13/01)


HIV Drug Resistance

Treatment of HIV patients with highly active antiretroviral therapy (HAART) can reduce plasma viremia to below the limits of detection by current ultrasensitive assays in many patients.

However, recent studies using specialized techniques have shown that virus production continues at a very low level even in patients with "undetectable" levels of plasma virus. In addition, many patients have isolated low-level positive plasma HIV-1 RNA determinations, or "blips." The source of this low-level viremia in the setting of seemingly effective HAART remains unclear. Understanding whether the continued release of virus into the plasma of patients with undetectable plasma HIV-1 RNA is associated with the gradual evolution of drug resistance is important in the design of treatment strategies.

This study was designed to determine whether the low level of viremia that can be detected with specialized methods in HAART patients reflects the presence of initial resistance mutations to one of the drugs in the current regimen. The researchers developed a method for amplifying and sequencing the HIV-1 pol gene from the very small number of virus particles in the plasma of patients receiving HAART who have a plasma viral load of less than 50 copies/mL. To determine whether low-level viremia requires the development of drug resistance mutations, they used the method in a cross-sectional analysis of a group of patients who had prolonged suppression of viral replication with HAART and less than 50 copies/mL of HIV-1 RNA at the time of the study.

Subjects were 18 HIV-1-infected patients (seven children and 11 adults), enrolled in a longitudinal study of HIV-1 reservoirs, who had suppression of viral replication while receiving protease inhibitor-containing combination therapy. Two patients (one adult and one child) with less optimal suppression of viral replication were included to assess virus predominating when plasma HIV-1 RNA levels are low but detectable. (Journal of the American Medical Association, 07/11/01, Vol 286;No 2: P 196-207; Monika Hermankova et al.)


African Americans and "The Deadly Secret"

At the end of the second decade of the AIDS epidemic, African Americans are experiencing a steady rise in infections, especially among men ages 23 to 29 who have sex with men. This tragic increase is puzzling in light of the slow down in rates among white gay men, yet not so puzzling when seen in the light of a tradition of homophobia and negative attitudes towards African American men in religious communities. Recent research makes clear that unacknowledged homosexual activity may be a secret that kills.

According to Dr. John Peterson, psychology professor at Georgia State University, who is conducting a study of gay and bisexual men ages 15 to 25, "It's pretty well-known that half of the cases of AIDS among African American men have been among men who have sex with men." Peterson's research, published in the 1998 AIDS Education and Prevention journal, shows that African American bisexual and gay men believe they face greater homophobia than whites and they respond to it differently than whites.

While white men who have sex with men are more likely to leave families and communities, particularly in rural areas and small towns, and move to gay communities in major cities like San Francisco, Atlanta or New York, this is not true of black men. There is no such thing as a gay community for African American men. "The African American community provides them support to deal with racism they experience in the general population and in the white mainstream gay community," Peterson said.

For many years, according to Pernessa C. Seele, founder of Balm in Gilead, a New York AIDS advocacy organization, religious leaders in the black community used the Bible to justify their treatment of gays and lesbians. "That's the throat-hold on this issue," she said. The grip of intolerance is beginning to change in cities across the country. "One of the things that allows us to respond effectively to the issue of homophobia is, we have a clear biblical mandate to love one another," said the Rev. Edwin C. Sanders II, pastor of Metropolitan Interdenominational Church in Atlanta. At a meeting of national African American leaders who met in Atlanta recently, the agreed-upon crucial culprit in the spread of HIV/AIDS was homophobia. "We need to get our heads out of the sand," Rev. Charles E. Wells, Sr., pastor of Flipper Temple AME Church said. "This epidemic affects just about every family in our congregation."

The double lives of African American men afraid to confront their sexuality also tragically affect African American women. According to the CDC, for African American women, who make up 19 percent of all new HIV infections and 64 percent of new HIV infections among women of all races, the leading cause of exposure to HIV has been heterosexual activity. The most likely scenario in many cases in women is that their partner contracted the virus after having sex with another man, said Dr. Helene Gayle, director of the CDC's National Center for HIV, STD and TB.

"It gives a clear picture that this is an important issue and one we must grapple with if we're going to reach young men of color who are having sex with other men," she added. (The Atlanta Journal Constitution, 07/08/01, Gracie Bonds Staples)


AIDS Fighters Redouble Vaccine Effort

Despite successes in deciphering HIV and probing for its weaknesses, the scientific stumbling blocks to AIDS vaccine development remain daunting. But with HIV running rampant in the developing world, public health experts see a vaccine as the best hope for slowing its spread. That is giving renewed urgency to the hunt for a safe, effective immunization against HIV. It's about time, says Dr. Seth Berkley, president of the International AIDS Vaccine Initiative. "The fact remains that 20 years after the epidemic began, no vaccine is available," Berkley said. "This is a disgrace."

The fate of AIDS vaccine research largely mirrors that of other vaccine research, which is expensive, uncertain and yields fewer profits for drug manufacturers than treatment drugs. Since early in the epidemic researchers found that HIV mutates easily; by the late 1980s and early 1990s the emphasis in AIDS research had switched from finding a vaccine to developing treatments for AIDS patients.

The UN special session on AIDS last month concluded with a recommendation for increased funding to accelerate vaccine research. Currently, worldwide spending on vaccine research totals about $400 million, or two percent of the $20 billion spent on AIDS research. In the United States, the AIDS vaccine research budget at the National Institute of Allergies and Infectious Diseases is set to increase from about $100 million five years ago to $350 million next year.

AIDS experts emphasize that when an AIDS vaccine is developed it must be affordable for people in developing countries, where the proper distribution of such a vaccine will likely necessitate dramatic improvements in medical facilities. In this country, a vaccine would probably be given first to high-risk groups, such as homosexual men and intravenous drug users.

If such immunization proved highly effective with few side effects, someday it could be given as routinely as measles and tetanus shots. (Chicago Tribune, 07/18/01, Stevenson Swanson)


Circumstances at HIV Diagnosis and Progression of Disease in Older HIV-Infected Americans

Patients older than 50 years represent 11 percent of all AIDS cases in the United States. Previous studies of older HIV-positive individuals have been conducted on small or non-representative samples. The investigators studied the circumstances at diagnosis and disease progression by examining survey data from a probability sample of 2,864 HIV-infected individuals using health care facilities covered by the HIV Cost and Service Utilization Study (HCSUS), a nationally representative sample of HIV-infected individuals in the United State. Data sets were obtained from 2,864 subjects completing baseline interviews. Eighty-six percent (2,466) of participants completed the first follow-up survey and 79 percent (2,267) were available for the second follow-up interview. The analysis included interview data on patient demographics and circumstances of first diagnosis, as well as clinical characteristics at baseline and follow-up interviews.

Results of the study indicate that individuals older than 50 years, particularly those of non-White ethnicity, are more likely to be diagnosed with HIV infection after they have symptoms. Non-Whites are less likely to have clinical AIDS at baseline. During the follow-up of 14.4 months, disease progression in this group was more rapid than for Whites.

Prior studies have shown knowledge deficits regarding HIV risk factors among providers and patients that may lead to overlooking risk-taking behavior among older populations. Disparities in progression to disease might be explained by the fact that older non-Whites die more quickly once they have AIDS, as some studies have suggested. "Alternatively," according to the authors, "non-Whites may receive less effective antiretroviral therapy, contributing to less clinical improvement." Later diagnosis and potentially more rapid disease progression among older non-Whites are troubling. Improvements in the identification of HIV-infected individuals and prevention education are needed among older non-Whites. (American Journal of Public Health, 07/01/01, Vol 91; No 07: P 1117-1120; David S. Zingmond, M.D. et al.)


New York City Says Inmate Care Fails in Most Contract Categories

New York City's Health and Hospitals Corporation said this week that the health care company which had been awarded $314 million to care for inmates, had failed to adequately provide services in its first three months on the job. In a comprehensive review of Prison Health Services, city officials found inadequate services in 30 of 33 categories and penalized the private company $100,000. The review found that the company had failed to give all pregnant inmates HIV tests and had not properly treated inmates for the threats of TB and STDs. Prison Health Services provides care to 13,500 inmates at 12 city jails.

New York City's medical treatment of inmates has been controversial for several years. Last year, the city ended a contract with St. Barnabas Medical Center after three years of disagreement over costs, accountability and after patient deaths at the jails. The deaths resulted in a criminal inquiry that is continuing.

Prison Health Services, a corporation with $400 million in annual revenues, cares for more than 175,000 inmates in 27 states and Washington. There have been many reports of severe staffing problems and substandard care in Pennsylvania, Georgia, Florida, Washington and elsewhere. Inmates in New York have been troubled by the company's record nationally and said they remained concerned about issues like staff turnover at Rikers Island Detention Complex where, under Prison Health Services, there have been three medical directors since the first of the year.

Ernesto Marrero Jr., executive director of Correctional Health Services, the city agency that conducted the review, said that the review was tough and thorough. City officials conceded, however, that the company had improved recently and said they believed it had turned a corner after a rocky start. Company officials pointed to the rigors of their service contract and said they were pleased with their performance, given the difficulty of taking control of medical services in a sprawling system of jails. (New York Times, 07/19/01, Katherine E. Finkelstein)


Study Finds Condoms Usually Block HIV

Condoms are usually effective in fighting the spread of HIV and gonorrhea, but there is not enough evidence to say for certain that they protect against other STDs, federal health officials concluded in a draft report released today. "To definitely answer the remaining questions about condom effectiveness for preventing STD (sexually transmitted disease) infections will require well-designed and ethically sound clinical studies," said the report by the National Institutes of Health. The report does not draw conclusions about the adequacy of condoms in reducing the risk of disease "other than HIV transmission in men and women, and gonorrhea in men," but it did say that one in five American adults had an STD. (New York Times, 07/20/01, Associated Press)


Study: Brooklyn at Center of Epidemic

A recent study shows that Brooklyn residents are at the center of the AIDS epidemic and are dying of AIDS complications at a much higher rate than the national average. "AIDS is, and will remain for the foreseeable future, a distressing part of our borough's life," wrote Dr. John C. LaRosa, president of the Brooklyn-based State University of New York (SUNY) Downstate Medical Center, in a report called "Report Card on HIV/AIDS." "Brooklynites are 3.5 times more likely to have the disease than their fellow Americans. More than half the AIDS cases in the borough are among blacks. ...More children live with AIDS in Brooklyn than any other borough. And most adults, men and women, living in the borough trace their infection to injection drug use."

According to the report: AIDS is the third leading cause of death in Brooklyn, even though it is not among the top 10 causes of death in New York state or the nation; more than half of all AIDS cases in Brooklyn can be traced to intravenous drug use; and women living in Brooklyn are far more likely to be diagnosed with AIDS than women living elsewhere in the city, state or nation.

The report also said that between 1991 and 1999 new AIDS cases among women living in Brooklyn rose from 27.4 percent to 35.4 percent of total adult AIDS cases.

The report was based on data from the CDC and the New York City and state health departments, said Dr. David Warren of SUNY. Warren, who is the medical director of SUNY Downstate Medical Center's Special Treatment and Research program, said that HIV/AIDS is prevalent in Brooklyn because, "As a whole, the borough has been slow to respond [to AIDS]." He said the "message isn't getting out" and that "the amount of outreach for testing really lags behind." Reaching out to the diverse populations impacted by HIV/AIDS can also be challenging, he added. (New York Blade, 07/13/01, Inga Sorensen)


Prevalence and Predictive Value of Intermittent Viremia With Combination HIV Therapy

In HIV-infected patients, antiretroviral therapy (ART) is directed at achieving and maintaining HIV RNA levels below the limit of detection of currently approved assays. A lower nadir of HIV RNA in response to therapy is an independent predictor of long-term virologic suppression. When patients interrupt therapy or when the potency of a regimen is reduced, abrupt elevations in HIV RNA levels are observed. However, transient smaller elevations in HIV RNA levels are also frequently observed in patients who maintain HIV RNA levels of less than 200 copies/mL with potent ART. These transient episodes have been described as intermittent viremia or "blips." The HIV RNA nadir resulting from ART has been established as an important predictor of long-term virologic suppressions, but the effects of intermittent viremia on rates of viral suppression have not been established.

To determine the prevalence and predictive value of intermittent viremia, the researchers conducted a retrospective analysis of subjects in the AIDS Clinical Trials Group (ACTG) 343 and the Merck 035 trial. Of the 241 ACTG 343 patients, 101 received triple-drug therapy throughout the study. The 13 Merck 035 subjects had virologic suppression after six months of indinavir-zidovudine-lamivudine.

Intermittent viremia occurred in 96 (40 percent) of the 241 ATCG 343 patients, of whom 32 (13 percent) had 2 consecutive HIV RNA values >50 copies m/L during the median 84 weeks of observation. (Median duration of observation after first intermittent viremia episode was 46 weeks.) Of the 101 individuals receiving triple-drug therapy throughout, 29 percent had intermittent viremia. The proportion of episodes occurring during the maintenance period was 64 percent for the entire cohort and 68 percent for the group not receiving triple-drug therapy throughout vs. 55 percent for those who did (P=.25). Intermittent viremia did not predict virologic failure: 10 (10.4 percent) of 96 patients with 20 (13.8 percent) of 145 patients without intermittent viremia had virologic failure (relative risk, 0.76; 95 percent confidence interval [CI], 0.29-1.72). In a Cox proportional hazards model, the risk for virologic failure was not significantly greater in the ACTG 343 patients with intermittent viremia (hazard ratio, 1.28; 95 percent CI, 0.59-2.79). (Journal of the American Medical Association, 07/11/01, Vol 286, No 2: P 171-179, Diane V. Havlir, M.D. et al.)


Pulmonary Hypertension Associated With HIV Infection

It has been established that the incidence of pulmonary hypertension in HIV-positive persons is several thousand times greater than in the general population. Although the pathogenesis of HIV-associated pulmonary hypertension remains unknown, it appears to occur independently of other risk factors associated with pulmonary vasculopathy, such as chronic hepatitis C infection and intravenous drug use. There appears to be no correlation between either CD4 count or the stage of HIV infection and the prevalence or severity of pulmonary hypertension. Among reported cases, CD4 cell counts have ranged from 0 to 937/mm3 (mean, 269/mm3).

The etiology of primary pulmonary hypertension (PPH) remains unknown, but its development is thought to require both a genetic predisposition and a precipitating event. At the core of the pathogenesis is evidence of endothelial cell dysfunction manifested by enhanced ascoconstrictor synthesis, diminished vasodilator production and enhanced thrombogenesis. Initially, it was thought that HIV might play a direct role by infecting and injuring endothelial cells; however, evidence for direct involvement by the virus has been lacking. It has been suggested that the increased incidence of pulmonary hypertension in patients with HIV might be due to an indirect role of the virus, stimulating the host to release proinflammatory cytokines or growth factors, which result in pulmonary hypertension in genetically predisposed individuals.

Few reports describe the efficacy of treatment for pulmonary hypertension in HIV. There have been case reports of progression of pulmonary hypertension despite effective antiretroviral therapy and low viral load. Rich et al. estimated that approximately 25 percent of patients with PPH may respond favorably to calcium channel blockers with both a reduction in pulmonary vascular resistance and a drop in pulmonary artery pressure. Few data are available on the prevalence of vasodilator responsiveness among patients with HIV-associated pulmonary hypertension. In one series, none of the fives cases of HIV-associated pulmonary hypertension responded to calcium channel blockers, and intolerable side effects occurred in four of the cases. Acute responses to epoprostenol are similar to those among non-HIV-infected individuals, but the benefits of long-term, intravenous treatment with epoprostenol in HIV-infected patients are unknown.

"Additional studies are needed to better define the effect of HAART [highly active antiretroviral therapy] on HIV-associated pulmonary hypertension. With the increased use of HAART for HIV, it will be interesting to note whether a measurable change occurs in prevalence of HIV-associated pulmonary hypertension.

"Investigations of the effects of vasodilators on the natural history of HIV-associated pulmonary hypertension are also needed. Especially important is understanding the effects, if any, of therapy with prostacyclin and its analogues on HIV viral load and on HAART," the researchers wrote.

"In the interim, without supporting evidence, we recommend screening with transthoracic echocardiogram for all HIV-infected persons with unexplained shortness of breath or syncope.

Furthermore, we recommend the initiation of combination antiretroviral therapy in all HIV-infected patients with pulmonary hypertension irrespective of CD4 counts or viral load," the authors concluded. "Initiation of continuous intravenous epoprostenol for all patients with NYHA class III or IV symptoms who fail to respond to calcium channel blockers seems prudent." (Southern Medical Journal, 06/01, Vol 94; No 6: 635-639, Leonardo Seoane, M.D. et al.)


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