Newsline

1. Second-Class Citizens
   
2. Through Thick and Thin
   
3. Breathing Easier
   
4. A is for Africa
   
5. Climbing a Mountain? Take a Water Bottle!
   
6. A Grapefruit a Day
   
7. The Best Policy
   
8. #2 NNRTI 4 U
   
9. Clinton Administration Proposal
   
10. A New Concern
    
11. Health Insurance to Go
    
12. Lip Service

    
    

Second-Class Citizens

Women are not receiving equal treatment for HIV

Infection with HIV is known to increase the risk of several cancers, including non-Hodgkin lymphoma, Kaposi's sarcoma, and anal cancers. Invasive cervical cancer is not on that list, although many AIDS experts are convinced that HIV infection does increase the likelihood that women will develop this cancer. At the National AIDS Malignancy Conference, Harold Jaffe of the Centers for Disease Control and Prevention offered a grim explanation for this discrepancy: many women with HIV simply do not live long enough for their cancerous cervical lesions to become invasive. In those who do, however, the cancer is very aggressive. For that reason Jaffe and others recommend that women with HIV be screened frequently for cervical cancer, either by Pap test or coloscopy.

Although advocates for people with HIV have been insisting for years that "women die faster" and have been demanding that the situation be addressed, there continue to be strong reminders that little has actually changed. Researchers at last month's National Conference on Women and HIV noted that while the death rate for men with AIDS fell 16% in 1996, the death rate for women with AIDS rose 3%.

Conference participants attributed this disparity to the fact that women with HIV do not have the same access to cutting-edge treatments as men do -- and that even when women do have equal access, they do not always respond to therapy in the same way. This is due in part to the fact that most clinical trials enroll many more men than women. As a result, much of what we know about how a newly-approved drug works is based on how men respond to that medication. This does not always tell us if women will respond to the same dose of the drug, will experience the same side effects, or will enjoy the same benefits.

What this means for you:

Doctors have been slow to recognize the unique ways in which HIV affects women's bodies, and consequently women are often started on antiretroviral therapy later, and treated less aggressively, than men. To compensate for these failings of the current healthcare system, women with HIV must be particularly vigilant about noting changes in their clinical status, and they must be insistent about receiving prompt and appropriate treatment.

Victoria A. Cargill, M.D.
University Hospitals of Cleveland

Through Thick and Thin

New -- and thicker -- polyurethane condom is less prone to tearing

A recent issue of AIDS Alert reveals that in May 1996 the maker of the Avanti brand polyurethane condom replaced its original model with a thicker version. The manufacturer, London International Group, made that change at the request of the F.D.A. after studies showed that the original Avanti condom, first sold in 1994, had a breakage rate four times higher than that of latex condoms.

Although it knew of the breakage problem before May of 1996, the F.D.A. allowed London International to continue to sell the original Avanti condom because it was the only non-latex condom that prevented transmission of HIV -- which made it an important option for people allergic to latex. In fact, Avanti was approved by the F.D.A. only for use by people with latex allergies, a qualification noted on Avanti packaging by often overlooked by those who bought the condoms.

When it was introduced, Avanti was hailed as an alternative to latex condoms. It conducted heat, could be used with oil-based lubricants, and was thinner, allowing for greater sensitivity. Unfortunately, that thinness led to breakage. London International now places a sticker on each box of its new, thicker condoms to alert prospective purchasers that the condom is only approved for use by people allergic to latex.

Breathing Easier

A new means of identifying those who may need TB prophylaxis

A recent Italian study of tuberculosis and AIDS suggests that there is a relatively simple way of telling if a person with HIV is at increased risk for developing TB. Results of the multicenter Gruppo Italiano de Studio Tuberculosi e AIDS show that when people with HIV are given the standard skin test for TB, the size of the response is a good indication of how likely they are to come down with the disease.

In this study people with test reactions that were 5 millimeters or larger in total size were much more likely to develop active TB. Based on this finding, the researchers recommend prophylaxis against TB infection for all those with reactions larger than 5 millimeters. Unfortunately, many people with HIV, especially those with low CD4 counts, simply do not respond to the TB skin test. For these individuals, susceptibility to TB must be determined by other means.

A is for Africa

Vitamin A deficiency and mother-to-infant transmission of HIV

Several years ago, studies conducted in Africa indicated that women who had low levels of vitamin A were at increased risk of passing HIV to their offspring during pregnancy or at birth. Pregnant African women with HIV were therefore encouraged to take vitamin A supplements, to reduce the likelihood that they would transmit the virus to their babies. It now appears that these findings do not hold for women who live in countries where vitamin A deficiency is not a major health problem. A team of researchers in this country has found that there is no correlation between vitamin A levels and mother-to-infant transmission in pregnant American women with HIV. Therefore, women who live in the U.S. -- African-American women included -- should not take vitamin A supplements in hopes of stemming transmission of the virus.

Climbing a Mountain? Take a Water Bottle!

A timely reminder that Crixivan® -- now widely available -- must be taken with lots of fluids

Merck & Company has stepped up production of its protease inhibitor, Crixivan® (indinavir), and this drug is now available through local pharmacies. Until recently Merck was obliged to restrict the distribution of its new drug because a temporary shortage of manufacturing facilities allowed the company to produce only a limited supply of Crixivan. Merck feared that the relative scarcity of the drug might at some point prevent people who had started on Crixivan from getting refills of the drug. This was a matter of real concern, given how rapidly HIV can become resistant to the protease inhibitors if dosing is interrupted. For that reason Merck made Crixivan available only through Stadtlander's, a Pittsburgh-based mail-order pharmacy.

Merck has also stepped up its marketing of Crixivan, and in the process the company has broken new ground in the advertising of anti-HIV medications. Multipage color ads for the drug, which feature a mountain-climbing motif, recently began running in such mainstream magazines as Spin, Men's Fitness, Vibe, and Details.

The rock-climbing images being used to market Crixivan may strike some of the people taking the drug as ironic -- because taking this protease inhibitor can lead to the formation of kidney stones. Chemical analysis of kidney stones passed by patients whose antiretroviral regimen includes Crixivan reveals that the core of these stones is made up of crystals of the drug, so there can be no question that Crixivan is responsible for their formation.

What this means for you:

We have long known that Crixivan can cause kidney stones in a small but significant percentage of the patients who take this drug. These stones can develop as early as one week after therapy is initiated, or as late as five months. People who are taking Crixivan must remember to drink at least six full glasses of water a day, every day. This will help to prevent the formation of stones in patients taking this protease inhibitor.

Judith A. Aberg, M.D.
San Francisco General Hospital

A Grapefruit a Day

Grapefruit juice does increase absorption of some drugs

For years anecdotal reports have suggested that taking certain medications with grapefruit juice somehow increases their effectiveness. Those who scoffed at those reports should read a study that was recently published in the Journal of Clinical Investigation. It confirms that there is, in fact, a scientific basis for the observation that grapefruit juice promotes the absorption of a number of drugs, among them certain sedatives and antiretroviral agents. Some ingredient in grapefruit juice -- researchers haven't yet determined the specific substance -- apparently reduces the amount of a specific enzyme, known as CYP3A4, in the small intestine... and decreased levels of this enzyme allow for better absorption of some medications. The effect was noted not just in people who drank an 8-ounce glass of grapefruit juice whenever they took medications but in those who simply drank three 8-ounce glasses of grapefruit juice in the course of the day.

What this means for you:

This finding is certainly intriguing, but it does not mean that you should now begin drinking massive quantities of grapefruit juice in order to increase absorption of your medications. The amount of grapefruit juice consumed by these study subjects -- three 8-ounce glasses a day, taken with or without medications -- seems to increase the availability of certain antiretroviral agents. The trouble is that dramatic increases in the absorption of certain drugs taken by people with HIV -- ritonavir, rifabutin, and clarithromycin, for example -- can boost circulating levels of those drugs to toxic levels. And there is evidence to suggest that those levels are more likely to fluctuate if an individual's intake of grapefruit juice fluctuates.

Before you add quantities of grapefruit juice to your daily diet, you should discuss this step with your doctor. And, whatever you decide to do, you will want to be consistent about it, keeping your daily intake of grapefruit juice as nearly constant as possible.

Paul A. Volberding, M.D.
Editor-in-Chief

The Best Policy

Life insurance is now something people with HIV can buy as well as sell

In yet another sign of just how much the protease inhibitors have changed the landscape of AIDS, people with HIV can now buy life insurance for the first time since the discovery of the virus. The Wall Street Journal reports that Guarantee Trust Life Insurance Co. has become the first company in America to offer such a policy. The policies are expensive -- $300 a month in premiums for a $50,000 policy -- and they are not available to everyone with HIV. The company will only sell the policies to people who have demonstrated at least nine months of strong, positive response to combination therapy. And for now the policies are only available to people in Guarantee Trust's home state of Illinois. Other insurers are expected to watch the situation closely to see if the policies are profitable for Guarantee Trust. We will also be watching, and we will keep you informed of developments.

#2 NNRTI 4 U

F.D.A. approves delavirdine for use in combination therapy

The F.D.A. has approved a second member of the non-nucleoside reverse transcriptase inhibitor class of anti-HIV drugs. Pharmacia & Upjohn's Rescriptor® (delavirdine) thus joins Roxane Laboratories' Viramune® (nevirapine) as an alternative to nucleoside analogs in antiretroviral "cocktails." Rescriptor's approval was delayed for months while the F.D.A. weighed conflicting reports on its efficacy. To date this NNRTI has been studied in conjunction with older nucleoside analogs like AZT (Retrovir®), but it has not yet been studied in combination with any of the protease inhibitors.

Clinton Administration proposes extending Medicaid benefits to people with asymptomatic HIV

Policy change will make protease inhibitors available to thousands who have not yet developed AIDS

At present, Medicaid begins to cover the cost of antiretroviral therapy for the indigent and uninsured only when they develop full-blown AIDS -- which means that these individuals have to get sick before they can get drugs to make them better. This Catch-22 situation may soon be resolved, however, because the Clinton Administration has proposed a plan that would expand access to Medicaid-funded combination therapy to include low-income individuals who have tested HIV-positive but have not yet developed any symptoms of AIDS.

Fortunately for the tens of thousands of Americans who fall into this category, it will not be necessary to obtain Congressional approval to change the Medicaid law: President Clinton already has the authority to expand current coverage, by authorizing the Department of Health and Human Services to conduct so-called demonstration projects on a state-by-state basis. Vice President Gore, who requested the studies that led to this policy change, has noted that these demonstration projects may save the government money in the long run, by reducing the number of times that people with HIV need to be hospitalized. And, he adds, this policy change "will certainly save lives."

According to a spokesman for H.H.S., there is a strong public-health rationale for providing this expanded coverage, quite apart from the obvious humanitarian reasons: People who are being treated with protease inhibitors are less infectious, because their viral load is lower, and therefore they are less likely to transmit the virus. But the real virtue of this heartening change in policy is that it will make these powerful drugs available to people who are still able to work and eager to work -- a boost to their morale and to the tax base as well.

A New Concern: CMV in People with High CD4 Counts

Immune rebound resulting from combination therapy may not prevent retinitis

Some months ago you started a multidrug antiretroviral regimen that included a protease inhibitor, and your CD4 counts have skyrocketed: They're up more than 90 from their all-time low and they're still climbing, albeit more slowly now than they did at first. How much protection do these new CD4 cells offer you? Are they as good as the ones you lost when your counts began to fall?

No one yet knows the answers to these questions. It seems clear that combination therapy does restore some immune function -- because people on these powerful new drug regimens are experiencing spontaneous resolution of a range of HIV-related opportunistic infections, including treatment-resistant thrush, crypto, and even PML. But it also seems clear that these new CD4 cells are not as effective as the ones destroyed by the virus.

The proof of this comes from a study conducted at U.C.S.F. in patients on potent triple-drug combination therapy. All of these patients began the study with very low CD4 counts. With treatment, their CD4 counts rose well above 50, which is considered the "breakthrough" point for CMV infections. Although all these patients were theoretically out of the danger zone, 5 of the 76 did develop CMV retinitis -- which suggests that combination therapy does not provide protection against CMV in individuals who have low CD4 counts at the beginning of therapy.

What this means for you:

Initially, anyway, new CD4 cells lack sufficient "memory" to mount a full-scale attack on the pathogens that cause opportunistic infections. There is evidence that these new CD4 cells do regain some of that lost memory over time, but until they do they cannot be fully trusted to provide protection against these infections. This is why it is so important that people with HIV not abandon the prophylaxis regimens that protect them against OIs like CMV, even if their CD4 counts rise well above the supposed threshold for breakthrough infections.

Paul A. Volberding, M.D.
Editor-in-Chief
San Francisco General Hospital

Health Insurance to Go

New rules help people with HIV when they change a job or lose one

Following up on the Health Insurance Portability and Accountability Act of 1996, the White House has announced new regulations for insurance companies, regulations that make it easier for Americans to keep their health insurance if they change jobs or lose a job. Under the new rules, employers cannot deny health insurance to new employees who have pre-existing medical conditions, although they can require a 12-month waiting period before they begin covering those pre-existing conditions. The law also guarantees that people who have been covered by an employer's health insurance for at least 18 months before losing a job can obtain individual coverage.

The "portability" of such coverage has been praised by many as a way of keeping more Americans insured. It will also keep people with medical problems from being trapped in their current jobs just for the sake of maintaining their coverage.

While the regulations have certainly brought benefits, they have also led to new complications. The revised regulations require that employers, insurers, and authorities exchange more information than they used to, and this raises some concerns about confidentiality. Healthcare providers will have to be even more careful about maintaining the privacy of their clients, and they will need to get informed consent from patients at more points. Furthermore, healthcare providers will have to set up procedures that will allow patients to reconsider, as their health status changes, how much information about their condition they will permit providers to disclose to employers and insurance carriers.

Lip Service

Penciclovir cream eases outbreaks of oral herpes

In a recent study, penciclovir cream was shown to speed healing of herpes lesions on the lips of people with compromised immune systems. Over 2,200 people with a history of frequent outbreaks of oral herpes participated in the study, which was conducted by researchers at the University of Utah at Salt Lake City. Participants who received penciclovir cream had their herpes sores heal nearly a day faster than those given placebo. Pain was lessened as well, and the cream was effective whether used in the early stages of a breakout or later on. According to the researchers, penciclovir cream is the first treatment that clearly helps people who sufferer from recurrent oral herpes outbreaks.