President Bush’s budget proposal includes deep cuts for many health care programs for people without health insurance. While President Bill Clinton championed these programs, the present administration plans on phasing out these programs. Many state-based programs that provide drugs to uninsured people with HIV disease have placed new restrictions on benefits and enrollment due to being short on funding. Much of AIDS-related funding is through discretionary means whereby Congress must okay yearly. To alert Bush on your comments regarding HIV/AIDS service and research funding one may call the White House hot line at 202-456-1111, press 0 and leave your message.

Another lipodystrophy study conducted in Spain was published recently in the British medical journal, Lancet. All 494 patients were antiviral naïve at start of study and were started on protease inhibitor based cocktail. 17% of patients developed lipodystrophy at 18 months. Increased risks for lipodystrophy included female sex, increased age and duration of antiviral therapy. And while the cause appears to be multi-factorial problem, it was also observed that d4T (Zerit) was associated with significant risks for lipoatrophy (loss of fat) and indinavir (Crixivan) with increased central obesity (protease paunch). These findings are similar to other cohort studies.

The race for the development of a second generation NNRTI (non-nuke) continues, however, not without drama. While Dupont pharmaceuticals has DPC-083 in phase II studies, and phase III to begin by early summer, the company is up for sale, which leaves us with uncertainty regarding continued development of the drug. One hopes that the next purchasing company will have the experience and funding to keep up with Dupont’s track record, as it succeeded in developing Sustiva quickly and efficiently. On another front, the Agouron Pharmaceutical division of Pfizer has met with some stumbling blocks in trials with Caprivirine, their novel second generation non-nuke. Animal studies demonstrated some toxicity and inflammation to blood vessels (vasculitis). The sponsor is committed to developing this agent and is working with the FDA to complete its’ prior studies as well as further pharmacokinetic (blood drug levels) investigations. The next phase of clinical trials are hoped to begin early next year (2002).

Pegylated interferon combined with ribavirin for treatment of hepatitis C is more effective than standard interferon. The new Schering-Plough form of interferon was approved by the FDA in January with Hoffman La-Roche also on the way. The PEG interferon named because of its attached molecule of polyethylene glycol improves its’ half life enabling patients to dose the drug only once per week. The way in which the pegylated version’s approval occurred makes little sense as one can only obtain ribavirin with the older interferon version; ribavirin in combination with the PEG form is clearly superior. Other drug treatments for hepatitis C are also on their way. They include interleukin 10 as well as other inhibitors against hepatitis C such as protease inhibitors.

Drug resistant stains of HIV are increasing among the newly infected. In a study reported at the 8th Conference on Retroviruses and Opportunistic Infections held in Chicago this year, 14 percent of patients newly infected with HIV were found to have resistance to drugs of one particular class, increased from previously reported 3.5%. The tends showed that East Coast had increased resistance compared to the West Coast; the study was conducted in Dallas, Denver, San Diego, New York, Los Angeles, Birmingham, Seattle, Montreal and Vancouver. Two conclusion remains clear: drug resistant patients are spreading virus through unsafe sex and HIV-infected individuals need to continue practicing safe sex – “barebacking” is dangerous and persons promoting this form of unsafe sex are irresponsible.

More HIV+ individuals are looking at plastic surgery to help combat the disfiguring consequences of lipodystrophy, reported at the World Congress on Liposuction Surgery. Cosmetic surgeons are busy removing buffalo humps and other fat deposits. Cosmetic surgeons should work in cooperation with the HIV specialist or HIV antiretroviral prescribing physician.

Morbidity and mortality rates of aggressive squamous cell skin cancers appear to high in HIV positive patients. In a study reported at the American Society for Dermatologic Surgery and the American College of Mohs Micrographic Surgery and Cutaneous Oncology. Of the 10 patients who were doing well with HIV infection developed these aggressive skin tumors; 7 developed metastases and 5 died at an average of 11 months. The study suggests that HIV-positive individuals who develop aggressive squamous cell skin cancers should be treated with surgery followed by
radiation therapy.

The triple nuke regimen of AZT (retrovir) + 3TC (epivir) + Ziagen (abacavir) was found to be as effective in treatment of antiviral naïve HIV+ subjects as compared to the protease inhibitor based cocktail of indinavir (Crixivan) +AZT/3TC - recently published in the Journal of the American Medical Association (March 7, 2001). In this study 562 patients who had never experienced HIV antiviral treatment were randomly assigned in a double blind to the two cocktail regimens. Hypersensitivity reactions were reported in 7% of patients taking abacavir consistent with other studies. Interestingly, 2% of patients not taking abacavir, but on indinavir were reported by their investigator to have possible abacavir reactions based on the presence of rash alone.

Previous Whispers (September/October 2000)

Progenics Pharmaceuticals Inc's PRO 542 and Trimeris Inc's T-20 when used in combination may be a powerful new treatment against HIV. Both drugs effect HIV's ability to fuse with and ultimately stop HIV entry into the cell. Laboratory testing presented at the XIII International Conference on AIDS in Durban South Africa, showed an extremely potent response. While being used together, dosages were reduced to one-tenth the amount of each drug.

Cut or un-cut. In a report published by the New England Journal of Medicine (March 20, 2000) Ugandan and American investigators presented a study of heterosexual transmission of HIV among 415 couples. One of the findings included the fact that among circumcised male partners (50 men), no HIV seroconversions occurred vs 16.7% among 137 uncircumcised male partners. The finding that circumcision afforded protection against HIV infection may be explained by the foreskin being prone to microulcerations and provide increased surface area that is susceptible to HIV. This may also explain why there is a lower risk of female to male transmission of HIV in the US where most men are circumcised.

L-Carnitine therapy demonstrated encouraging findings in 4 patients treated for peripheral neuropathy (not to be confused with acetyl- carnitine being used for lipodystrophy). After 6 months of treatment there was observed improved skin innervation. Although this study findings, (presented at the 3rd International Workshop on Salvage Therapy in April 12-14, 2000), are limited by the small number of patients (20 patients are now continuing in this study) we hope that larger investigations are done to provide patients with additional treatment options for peripheral neuropathy symptoms.

Immunologic as well as anti-HIV benefit with interleukin 2. reported in the July 12, 2000 issue of the Journal of the American Medical Association. The study was conducted among 82 patients with CD4 T-cell counts ranging from 200-500 cells. Patients on IL-2 showed greater range of increased CD4 cells and more patients on the IL2 treated group (67% vs 36%) achieved viral loads of fewer than 50 copies/ml. This is the first study published to show enhanced control of viral replication with Il-2. See Dr Sirinek's article in this issue.

Dupont Pharmaceuticals is ready to launch a phase 2 study of their new second generation non-nucleoside reverse transcriptase inhibitor. After having less than superior effects from an earlier compound DPC 961, Dupont shifted their efforts to another agent in their pipline Гђ DPC 083. Dupont Pharmaceuticals is planning this phase II study at multiple sites in Europe, but at only 5 sites in the US; NorthStar will be one of the sites conducting the study.

IML (International Male Leather) weekend and circuit parties this summer has realized an increased incidence of STD's among the gay community in Chicago. Obvious unsafe sexual practices are becoming more commonplace. Although anecdotal, we have seen near epidemic proportions of STD's during this Summer. This has also been reported to us by other practitioners in Chicago. Besides the obvious toll on one's health, STD's are associated with a greater risk of HIV transmission to uninfected partners. We can not believe the carelessness and lack of responsibility that is becoming more rampant in the community. This is a sad commentary of our times.

Antiretroviral drug holidays is beoming of increased interest to HIV clinicians and researchers. Presently we believe this approach may also have relevance to patients currently overtly failing their regimens, so to encourage the re-domination of susceptible wild-type virus among selected patients. However this approach is also being investigated among stable patients with undetectable viral loads. But data to support the approach is small and very preliminary at best. This tactic may provide more drug free periods which decrease toxicity, improve adherance and decrease cost of treatment. It is refreshing to see the old conservative researchers becoming more creative while also stretching their necks out, once in a while.

Merck and Co, Inc has been investigating a novel protease inhibitor, MK-944 (formerly L-756,423) to be used with Crixivan in a single capsul. However, a recent Phase II study was suspended due to unexpected renal (kidney) toxicity with rats. Although this was not seen previously in a study with dogs or other pre-clinical studies, the study was suspended and further development with this agent was placed on hold. We hope that Merck remain committed to understanding this problem and perhaps continuing in their previous efforts to develop further treatment options for HIV infected patients.

Hydroxyurea's role in HIV treatment is still unclear. A recent study published from researchers from Johns Hopkins reported higher incidence rates of peripheral neuropathy among patients on hydroxyurea combined with d4T + ddI as compared with ddI/d4T alone. These finding add to the other accumulating toxicity of this drug which also include pancreatitis and not uncommonly seen Гђ hematologic adverse events.

Delavirdine (Rescriptor) may have finally found a niche in HIV therapeutics. Reported in a small study at the XIII International Conference on AIDS in Durban, South Africa, delavirdine, a non-nucleoside reverse transcriptase inhibitor appeared to enhance HIV protease inhibitor blood levels. When used in combinations with protease inhibitors, combination treatment with delavirdine appeared to result in reducing HIV load and increasing CD4 T cell count.

Previous Whispers (February/March 2000)

Institution of a new oppressive policy towards PWA's by Statlanders Pharmacy. A prominent mail-order pharmacy, Statlanders ( or 'Ratlanders' as some PWA's call them) that many HIV-positive patients utilize, has been recently acquired by Bergen Brunswig, Inc. They have recently changed their policy regarding patient burdens and responsibilities. As a result, some patients will now have to pay up front for the entire cost of their medications. One patient on growth hormone was quoted as saying that he may have to pay out up to two months in advance for his meds, which can amount to $15,000. Most patients do not have these financial resources. He was told by this company's patient liaison to go else-where for his business. Perhaps other patients should go elsewhere as well. Statlanders will probably lose much business. Other mail order pharmacies are not requiring up front payments and would be more than happy to accommodate former Statlanders clients.

The latest theory for the cause of fat redistribution or lipodystrophy ... that was evoked at recent medical meetings is its' relation to mitochondrial toxicity. Mitochondria is present in all human cells and is abundant in adipocytes (fat cells). Various anti-viral drugs commonly used for the treatment of HIV disease have been shown in the test tube to cause mitochondrial dysfunction. Still many HIV clinicians are uncertain of the link between mitochondrial toxicity and lipodystrophy.

Viral load resurgence was observed when triple therapy (HAART) was stopped. An attempt to cure AIDS via treatment with HAART with interleukin-2 failed reported in USA TODAY, quoting a recent article in Nature. After halting treatment, the virus rebounded, despite the fact that early indicators showed no detectable levels of virus in the blood, initially. It was hoped that IL-2 would activate any latent infected cells so that the activated cells would then be susceptible to HAART therapy. This approach may need to be redesigned to affect HIV infected cells in other body compartments such as brain and testicular tissues.

Low levels of HIV were found to be replicating in the blood and genital fluids, despite 'undetectability'by conventional viral load testing. The 22 patients in this study had undetectable virus in the blood using a hypersensitive assay for viral load to the level of less than 50 copies/ml but subsequently showed detectable HIV-RNA in selected cell types via more sensitive testing from blood plasma. The study, recently published in JAMA (782; 17: 1627-32), showed that 12 of the 22 patients had negative HIV-RNA levels in genital secretions but that 8 individuals had lower levels of HIV RNA. Presently and from this study, it is not clear where the low level of replication or residual infection is taking place, whether from lymph nodes, various immune system cells or other sanctuary sites.

New transmission of drug resistant HIV strains continue to appear. In a recent study (JAMA;282:1142-9) of 141 patients from San Diego, Los Angeles, Dallas, Denver and Boston, resistance mutations were seen in newly diagnosed patients prior to any antiretroviral exposure. One can't help believing that this situation will only accelerate over the not-too-distant future. Important to the community, safe sex should be maintained and stressed to everyone, including those individuals on antiretroviral therapy.

A new study shows high risk sexual behavior to be occurring in adolescent gay and bisexual males. The Centers for Disease Control and Prevention (CDC) conducted interviews among gay men in Baltimore, New York, Seattle, Miami, Los Angeles and San Francisco from 1994 through 1998. Over 40% of males surveyed said they engaged in unprotected sex within the previous 6 months. The growing complacency among young gay men may be due to the illusion that HIV does not necessarily progress to AIDS because of aggressive antiviral treatments. Many of these individuals have not lost friends to AIDS like older aged gay men. Additionally, young men who are just becoming sexually active may not be routinely testing for HIV. Stronger educational efforts should be implemented towards younger aged individuals.

Chinese herbal therapy was found NOT to show benefit, published recently in the Journal of AIDS. While many patients with HIV often pursue alternative therapies as treatment or as adjunctive therapy, this study is important and may help patients make a better decision on whether to add more pills and expense to their regimens. The study involved investigators from Zurich, Dublin and San Francisco and the 68 participants were patients with T-cells below 500 on stable antiviral therapy. The patients were then randomized to receive either pills containing 35 Chinese herbs or placebo for 6 months. The patients taking the herbs had more gastrointestinal side effects, however, there was no benefit in viral load, HIV symptoms nor quality of life.

New estimates for the start of the global AIDS pandemic has now been estimated back to the 1930's. Researchers presented their calculations at the Retroviral meeting in San Francisco on January 30, 2000. The calculations were based on a large computer database of HIV samples and genetic sequencing from the samples to calculate the evolutionary tree.

Dupont Pharmaceuticals Company has encountered a glitch in their research of their compound DPC 961. Preliminary findings showed the new compound to not be as advantageous nor superior to Sustiva. Thus they have shifted their efforts at developing yet another NNRTI. Phase II studies with DPC 083 are being planned; the hope is that this new compound may have the potential of being better tolerated and superior for patients failing treatment with other approved drugs.

A leading cause of death among priests has been attributed to AIDS. A new report coming out of Kansas City, where a prominent priest has recently died of AIDS has stipulated a large portion of deaths among the clergy to be secondary to HIV and AIDS. One leading AIDS caregiver has hypothesized that Catholic priests may be very closeted about their sexual preference thus inhibited about screening for HIV infection or seeking early treatment.

Previous Whispers (June/July 1999)

HIV Positive Women Have Higher Risks for Developing AIDS. Researchers from John's Hopkins have demonstrated that HIV-positive women with similar viral loads of males appear to have half the CD4 T cell counts of their male counterparts. Women may not be equal in HIV progression due to hormonal, biologic or anatomical differences. Other researchers in Switzerland and Italy have reported similar results. It may be inferred that HIV+ women should be treated more aggressively and earlier.

Early Detection of Kaposi's Risk. A new test is being developed to detect the presence of HHV-8 (herpes virus type 8) the virus believed to be the cause kaposi's sarcoma in AIDS. Although the incidence of KS is declined among patients treated with triple therapy many individuals that are untreated are still at high risk. The test may be used in addition to other screening tests for HIV positive patients that may aid in the decision making of starting on treatment for HIV.

HIV Suppression vs. HIV Cure. Researchers and physicians have been pendulum swinging from two vantage points. The hope of finding a cure via focused research on the treatment of latent (inactive) virus populations is tempered with the struggle of keeping HIV under control. Obstacles of resistance and trying to help promote adherence to difficult treatment regimens for some patients is a frequent daily labor for physicians and patients alike. Most believe that finding a cure is still a surmountable task that can be undertaken. While every HIV infected cell in the body may not be reachable with current antiviral drug therapy, there may be ways to strengthen the immune system to overcome HIV.

Less Than Standard. A national survey of HIV treatment conducted by the University of California at San Francisco discovered that one of every four patients received out-of-date treatment regimens. The study found that doctors treating less than 100 HIV patients were more likely to prescribe wrong combinations or delay treatments until patients were often sick. Managed care insurance companies unfortunately also promote this problem by attempting to encourage general doctors to care for HIV-infected individuals.

Liquid Norvir Sufferers. News regarding a new formulation of Norvir has arrived. The FDA has finally given Abbott Labs, the manufacturer of Norvir, the green light to make available the new form of its' protease inhibitor in gel capsule form for July 1999. Currently, patients on Norvir must endure the horrible taste while trying to dilute it with various foods and shakes, sometimes not suppressing its' gross after taste.

New HIV Class of Drug Soon to be Submitted. Gilead Sciences, the manufacturer of Preveon (adefovir dipivoxil) has announced plans to submit its' NDA (new drug application) soon for the marketing of this new antiviral agent . Preveon is the first antiviral in the nucleotide class and will be submitted for approval at one 60 mg tablet per day dosing. (Gilead Sciences' PMPA prodrug is the second agent in this new class and is also making its way through clinical trials). Initial trials with Preveon dosed at 120 mg per day, was found to demonstrate reversible but significant kidney toxicities. The 60 mg dose is reported by Gilead to have significantly less kidney side effects, while still maintaining important antiviral effect. An additional attribute of the drug is its' improved antiviral effect in patients who already possess resistance to 3TC.

New Protease Inhibitor Now on the Shelves. Amprenavir, being marketed by Glaxo Welcome under the name Agenerase (VX-141) is a new protease inhibitor has made it to pharmacy shelves this month. The new protease inhibitor is the one that can be taken with or without food, but at eight large capsules, twice per day. Many physicians and researchers view with pessimism the claim that Agenerase may still be effective in 55% of patients with resistance to other protease inhibitor agents.

Cigarette Smoking. A New study has revealed that smoking may be an additional health risk for HIV infected patients. The study published in the American Journal of Respiratory and Critical Care Medicine demonstrated that HIV-positive individuals who smoke have depressed levels of CD8-lymphocytes in the bronchial lavage fluid which may play a role in fighting HIV. Smokers were also shown to have lower levels of interleukin-1 in the bronchial fluid, important at fighting bacterial infections. The study may suggest and explain how HIV-positive smokers are more at risk for respiratory and lung infections such as bronchitis and pneumonia.

Remune (Salk Vaccine) Trial Terminated! The large multicenter study investigating the immune based vaccine therapy for HIV positive patients has been closed down. 2500 patients were enrolled. The company sited the opinions of the Data Safety Monitoring Board who believed that there was no significant differences in clinical endpoints between patients on treatment vs. the control group. Although the company states that new plans will be made for which to study this treatment vaccine so that it may eventually come to market, this remains to be seen. Currently, the findings that it improves certain immune functions has yet to be established as being clinically important