Slight risk associated with use of these potent drugs
The Food and Drug Administration has sent a letter to the nation's doctors, warning that protease inhibitors, the powerful new drugs that have revitalized AIDS care over the past year, can cause diabetes. But the F.D.A. is telling doctors not to stop prescribing protease inhibitors for their patients with HIV because the risk that an individual will develop diabetes from taking these drugs is so small. To date, only 83 cases of therapy-induced diabetes have been reported. Of these, 21 required hospitalization and six were serious.
Because the protease inhibitors have been widely available for only a short time, data on the frequency of this potential side effect of therapy is scarce, but the F.D.A. estimates that protease inhibitors may cause diabetes in 1 in every 1,000 (or perhaps even 1 in every 100) people taking these drugs. The four currently approved protease inhibitors -- saquinavir (Invirase®), indinavir (Crixivan®), ritonavir (Norvir®), and nelfinavir (Viracept®) -- will all be relabeled to warn of this possible complication of therapy.
What this means for you:
Don't panic. Diabetes is a readily diagnosed and treated condition, and your doctor will know what to do if you do develop this infrequent complication of protease inhibitor therapy. Diabetes responds to dietary modification and other life-style changes, and it can often be treated successfully with oral medications. More rarely, daily injections of insulin are required to bring it under control. You should not refuse to start taking a protease inhibitor -- or stop taking the one you have been prescribed -- simply because there is a small chance that this useful medication may cause diabetes.
The early warning signs of diabetes are increased thirst, more frequent urination, and itchy skin. If you develop any of these conditions, be sure to mention them to your primary care provider.
Multiple infections increase viral load
Researchers have long known that preventing sexually-transmitted diseases, and treating these STDs promptly and aggressively, helps prevent the spread of HIV -- because sores and other skin irregularities caused by STDs provide a way for HIV to enter the body. Now researchers at the University of North Carolina have discovered another reason to diagnose and treat STDs rapidly in people with HIV: HIV-positive men who also have another sexually-transmitted infection have eight times as much HIV in their semen as men with HIV alone.
These dramatically increased HIV levels in semen make the sexual transmission of HIV much more likely. Luckily, the study also showed that this increased risk of transmission can be easily reduced: When the men with other STDs were treated for those infections for just two weeks, the level of HIV in their semen declined to approximately the same level found the men without other STDs.
Valtrex prevents 86% of recurrent outbreaks
Glaxo Wellcome, maker of the leading anti-herpes drug, acyclovir (Zovirax®), has announced study results which show that the company's new anti-herpes drug, valcyclovir (Valtrex®), can prevent recurrent attacks of genital herpes in people with HIV. Valcyclovir is already approved for treating cases of genital herpes and shingles. Glaxo is now seeking F.D.A. approval to use the drug as prophylaxis against genital herpes attacks in people who have experienced one or more breakouts. In Glaxo's study of more than 1,000 people with HIV and genital herpes, valcyclovir prevented repeat herpes attacks in 86% of those on the drug.
Implant leads to dramatic decrease in disease progression
A recent study of treatments for cytomegalovirus retinitis, an HIV-related eye infection that can cause blindness, has shown that a ganciclovir-impregnated membrane, implanted directly in the eye, is much more effective in preventing disease progression than standard intravenous treatment with the drug. On average, study participants who received ganciclovir implants went 221 days without any significant worsening of their CMV retinitis, while those taking the drug intravenously experienced deteriorating vision after an average of 71 days.
The particular advantage of the implant (Vitracert®, made by Chiron Vision) is that its sustained-release formulation permits continuous dosing directly to the affected eye. This provides a near-constant level of drug at the infection site for the life of the implant. Intravenous treatment, by comparison, tends to result in relatively high concentrations of drug in the blood stream immediately after a treatment, and in a gradual decline in concentrations until the next treatment.
The Vitracert implant is surgically placed in the eye in a procedure that takes less than an hour, requires only local anesthesia, and can be done on an out-patient basis. Immediately following the surgery, patients often experience blurred vision, but this generally clears up within two to four weeks. When the implant's drug supply is depleted after six to eight months, a new implant can be inserted to replace it.
What this means for you:
Surgical insertion of one of these drug-impregnated implants results, on average, in an additional 150 days without significant deterioration of the patient's vision -- a marked advance over IV therapy. The implants do have one drawback, however: they are more likely to allow CMV to spread to the healthy eye. This is not as likely to happen with intravenous treatment, because CMV infection is systemic -- that is, it occurs throughout the body -- and IV therapy works throughout the body. The Vitracert implant, by contrast, is a localized therapy. It does a very good job of controlling CMV retinitis within the eye, but it is ineffective against CMV elsewhere in the body. For this reason I strongly recommend that patients who have one of these inserts implanted in an infected eye also take oral ganciclovir (Cytovene®, Roche Laboratories) to guard against the development of CMV infection in the untreated eye or elsewhere in their body.
Does your home care provider run background checks on its employees?
Next year, new federal regulations will be announced for home health care companies. Standards will be set for staffing, patient monitoring, the qualifications of administrators, and background checks on employees. A recent report in USA Today highlights the need for more stringent background checks. Currently, just 16 states require criminal background checks for home healthcare providers, and yet as much as 40% of the theft and abuse that occurs in home healthcare situations nationwide is committed by workers with previous criminal records.
While we are waiting for the new federal rules to be announced and implemented, people who need home care are urged to thoroughly scrutinize home healthcare companies. References should be checked, the local better business bureau should be consulted, and companies should be asked to show that criminal background checks are performed on all of their employees.
A new use for an old drug with a bad rep
A study conducted by the AIDS Clinical Trial Group has shown that thalidomide, a sleep aid infamous for causing severe birth defects, is an effective treatment for HIV-related ulcers in the mouth and throat. These so-called aphthous ulcers can be so painful for people with HIV that they make eating difficult, and this can lead to weight loss. In the trial, aphthous ulcers were completely healed in 55% of the 29 participants given thalidomide, as opposed to 7% of the 28 people on placebo. Even when patients' ulcers were not fully cured by thalidomide treatment, they reported a reduction in the pain caused by those ulcers, and a corresponding increase in their ability to eat.
Rising CD4 counts may not mean a restored immune system
With the widespread introduction of protease inhibitors and the adoption of triple-drug combination therapy as the standard of care for people with HIV, many individuals have seen their viral load drop significantly and their CD4 cell counts rise by 100 cells or more. These dramatic improvements have left many wondering whether people with HIV whose CD4 counts rise above the levels where prophylaxis against various opportunistic infections is recommended can stop taking those disease-preventing drugs.
Studies of the safety of discontinuing various prophylactic treatments are now under way. In the meantime, experts on one prevalent type of OI, lung infections, urge caution. Prophylactic treatment against Pneumocystis carinii pneumonia (PCP) is recommended for people with HIV whose CD4 counts are below 200, while prophylaxis against Mycobacterium avium complex (MAC) is recommended for those with CD4 counts below 50. The Lancet reports that experts who attended a symposium on HIV-related pulmonary disease advocated continuing prophylaxis against these diseases -- even when successful anti-HIV treatment boosts CD4 counts above the so-called breakthrough levels for these common OIs.
What this means for you:
PCP prophylaxis is neither complicated nor expensive, and patients whose CD4 counts were once below 200 -- and who therefore began prophylaxis against pneumocystis pneumonia -- are well advised to continue to take their Bactrim®, even if their CD4 counts rise well above that theoretical cutoff point. The same caution applies to patients who began MAC prophylaxis when their counts fell below 50.
We do not yet know if the CD4 cells that are regained through triple-drug therapy are as active and potent as the cells the patient lost before that therapy began. The evidence seems to suggest that the regained cells are not as potent, at least not at first -- and until we know more, we should all err on the side of caution.
Glaxo Wellcome makes its promising new nucleoside analog available to children as well as adults
People with HIV have been clamoring for GW1592, a nucleoside analog now in Phase II/III clinical trials. This promising new drug -- which its maker, Glaxo Wellcome, calls abacavir -- is already in high demand, even though it has yet to receive F.D.A. approval, based on the encouraging results of these early trials.
In particular, abacavir is being sought by people who have been on antiretroviral therapy for years and have developed resistance to older nucleoside analogs. The data collected to date suggest that abacavir can be used successfully in combination with AZT or d4T -- or in individuals who have developed resistance to AZT -- because it is not cross-resistant to either drug.
Another apparent advantage of abacavir is that it is the only drug in its class that penetrates the central nervous system and brain as successfully as AZT -- making it a valuable option for treating or preventing the neurological complications of AIDS.
Recently, Glaxo announced that it has made abacavir available for children with AIDS. The company has launched an open-label study of abacavir for children who are more than six months old but have not yet reached their fourteenth birthday. To be eligible, children must have advanced cases of AIDS that are not responding to any of the available therapies. Their CD4 counts must be equal to or less than 15% of their total T-cell count, and they must have a viral load greater than 100,000. Children with higher CD4 cell percentages or lower viral load are also being accepted, if they have HIV-associated neurological complications that are unresponsive to other antiretroviral therapies, particularly AZT. Doctors interested in enrolling children in the study can call Glaxo at (800) 501-4672 to get details about the program and register patients.
Glaxo is preparing a similar open-label study of abacavir for adults with AIDS. Eligibility requirements for adults are somewhat different than those for children: Adults must have CD4 cell counts of 100 or less and a viral load of at least 30,000, and they must have already failed antiretroviral therapy with two nucleoside analogs and one protease inhibitor.
Enrollment is also possible for people with HIV who have developed treatment-limiting toxicities on all of the commercially-available antiretroviral therapies. Unlike the pediatric study, the adult program will be conducted only at 65 specific trial sites.
Glaxo expects to have this program up and running by mid-August. Interested individuals can have their doctors call the toll-free number listed above to get further information and apply for enrollment.
What this means for you:
Abacavir (GW1592) is a new nucleoside analog that has shown particular promise, and been particularly well tolerated, in early clinical trials. The results of these pre-approval studies suggest that abacavir, when taken in combination with AZT, may achieve results comparable to those seen when AZT and 3TC are combined.
I provide readers with more information on abacavir -- and a number of other promising new drugs for people with HIV -- in the June, 1997 issue of HIV Newsline, in an article entitled "The Next Generation of Antiretroviral Agents."
Harold A. Kessler, M.D.
Back to the August 1997 AIDS Care contents page.
This article was provided by San Francisco General Hospital. It is a part of the publication AIDS Care.