Monthly Archives - September 2007

New HIV Drug Info- From Clinical Care Options

CCR5 Antagonists (Maraviroc and Vicriviroc)

CCR5 antagonists block viral binding to the CCR5 chemokine coreceptor. Several CCR5 antagonists have been tested in clinical trials.

In August 2007, maraviroc was approved for use in multidrug-resistant patients with R5-only virus. A phase IIb/III trial of this agent in treatment-experienced patients has been reported.[4,5] A phase IIb/III study of maraviroc in treatment‑naive patients with R5 virus has also been performed, and 48-week results were recently reported.[6]

A second CCR5 antagonist in development is vicriviroc. Week 48 phase IIb data from studies in treatment‑experienced patients with R5 virus have been presented.[7] Phase IIb studies in treatment‑naive patients were stopped by the data and safety monitoring board because of decreased efficacy vs efavirenz‑based therapy and an increased rate of viral tropism change among patients receiving vicriviroc.[8]

Advantages and Disadvantages of CCR5 Antagonists

Based on the data currently available for treatment with CCR5 antagonists, there appear to be certain advantages and disadvantages associated with their use. At this time, efficacy data for these agents show a clear advantage over placebo in treatment-experienced individuals who have R5-only virus detected at entry. Indeed, there are numerous reasons to consider using CCR5 antagonists in the later stages of disease. There will likely be no cross-resistance with other available agents such as NRTIs, NNRTIs, PIs, or enfuvirtide. CCR5 antagonists seem to be well tolerated and are orally administered.

Despite these advantages, data have shown that treatment-experienced patients who are in later stages of disease are more likely to have D/M or X4 virus, a setting in which these drugs have not shown antiretroviral activity. For any individual patient, there may be only a specific window of opportunity to benefit from one of these agents while he or she has R5 virus only, with the chance that D/M or X4-only virus will emerge over time. By contrast, other classes of antiretroviral drugs typically only lose activity when agents from the class are used and resistance develops. It is important to recognize that although short-term safety has been demonstrated in studies to date, it remains possible that pharmacologic blockade of CCR5 may have adverse consequences that become apparent only after long-term use of these drugs. The safety aspects of these drugs as well as the consequences of resistance development need to be assessed with long-term use. There may also be the concern about the emergence of D/M or X4 virus with CCR5 antagonist therapy. Finally, use of these agents will require a test for viral tropism, incurring additional cost.

Integrase Inhibitors

Integrase inhibitors target the viral integrase enzyme, which plays a critical role in the viral life cycle, as discussed in the accompanying module by Daniel R. Kuritzkes, MD. Although integrase inhibitors focus on a novel target enzyme, the principle of enzyme inhibition has been the most commonly used mechanism of antiretroviral therapy. Therefore, evaluating response to these agents should be more straightforward than evaluating agents with other mechanisms of action.

The integrase inhibitors that are the furthest in clinical trial development are raltegravir (formerly MK-0518) and elvitegravir (formerly GS9137). Currently, phase III trials of raltegravir in treatment‑naive and treatment-experienced patients are ongoing, and at the time of writing is being considered by the US Food and Drug Administration (FDA) for approval for use in treatment-experienced patients. Elvitegravir is in phase II development for treatment‑experienced patients.

There are significant differences between these 2 compounds. Raltegravir is metabolized by glucuronidation; therefore, while there are interactions with drugs that are metabolized by the CYP450 system, interactions with that have been observed with other PIs and NNRTIs are not thought to be clinically relevant. By contrast, elvitegravir is metabolized by CYP3A4 and may therefore have significant interactions with other antiretrovirals including PIs, NNRTIs, and possibly CCR5 antagonists. Elvitegravir can be pharmacologically boosted with ritonavir, allowing once-daily dosing, whereas raltegravir must be administered twice daily.

Integrase Inhibitors: Advantages and Disadvantages

The advantages of agents in the integrase inhibitor class are clear. It is a novel class with no known cross‑resistance with other agents. The agents act synergistically in combination with approved agents, at least in vitro. They target the third essential enzyme of HIV. Finally, these drugs can be given orally.

Regarding disadvantages, there are no long‑term data on adverse effects since these agents are relatively new and relatively few patients have been treated to date. Virologic failure appears to be associated with a high likelihood of the emergence of resistance mutations. Moreover, available evidence, although limited to date, suggests that considerable cross-resistance exists between raltegravir and elvitegravir.[20,21] A recent case report described 2 patients who switched from elvitegravir/ritonavir to raltegravir after virologic failure, but experienced no significant reduction in HIV-1 RNA level (Capsule Summary).[22] It is clear that these drugs should be combined with an effective OBR to minimize the risk of resistance and potential cross‑resistance

How Will We Use New Agents in Treatment-Experienced Patients?

Maraviroc has been approved for use in treatment-experienced patients; therefore, candidates for therapy will typically be those with more advanced stages of disease who are more likely to have D/M or X4 virus, a setting in which CCR5 antagonists are likely to have reduced or no activity. Another challenge is that it will be difficult to consider switching to maraviroc as a replacement for other agents in patients whose HIV-1 RNA is suppressed, because testing for viral tropism requires detectable viremia. Therefore, maraviroc is most appropriate for the subset of treatment-experienced patients who are experiencing virologic failure on existing therapy, who have no detectable D/M or X4 virus on a screening test for viral tropism, and who have other active agents available to use as part of an OBR.

Individuals who are treatment naive, on the other hand, are less likely to have a D/M-tropic or X4 virus and, therefore, have a better chance of being candidates for CCR5 antagonist therapy. However, in the recently reported results of the MERIT trial, maraviroc failed to meet criteria for noninferiority to efavirenz for the primary endpoint of HIV-1 RNA < 50 copies/mL. Likewise, a trial of vicriviroc was halted because of inferior efficacy compared with efavirenz in treatment-naive patients. These data suggest that further investigation of the use of maraviroc and vicriviroc in treatment-naive patients maybe needed before they can be considered for use in this patient population Integrase inhibitors will initially be used for treatment-experienced patients because the largest data sets involve this population of patients. Studies in treatment-naive individuals are also under way, and preliminary data certainly suggest that there may be a role for this class of drugs in these patients. Unlike CCR5 antagonists, there appear to be no specific considerations that argue for earlier or later therapy, since agents in this class should be effective regardless of when the agents are used. Dosing issues may affect the use of integrase inhibitors as initial therapy. For example, raltegravir, the drug that is in the most advanced stage of clinical development, is dosed twice daily whereas once‑daily options are generally favored in the earlier stages of disease and, indeed, throughout treatment. Although elvitegravir is a once-daily drug and can be given with ritonavir, the implications of the use of low-dose ritonavir without another PI must be considered. There is little experience with this particular situation, and the potential risk of selecting for PI resistance if virologic failure occurs must be explored in the future. Consistent with general principles, this class of drugs will be most active when used in conjunction with other active drugs. Therefore, strategic thinking is necessary when considering the introduction of novel drugs into treatment regimens. It is crucial to preserve as many active drugs as possible and to combine these with new drugs, hopefully enabling us to achieve undetectable HIV-1 RNA even in the most treatment‑experienced patients, as recommended in the US Department of Health and Human Services and the International AIDS Society-USA guidelines. Etravirine, a new second-generation NNRTI, has demonstrated potent activity when combined with other active agents in patients who have experienced virologic failure while receiving efavirenz or nevirapine. Patients who may benefit most from this drug are those who stopped NNRTI-based therapy in the past after developing only 1 or 2 NNRTI resistance mutations, or patients who were not considered candidates for NNRTI-based therapy because of transmitted NNRTI-resistant virus. Those with a greater number of NNRTI mutations may derive less benefit from this agent. The recently reported mutation score may help in identifying which individual patients are most appropriate for this agent. Furthermore, the resistance data emphasize the importance of discontinuing the use of currently approved NNRTIs in a failing regimen to minimize the risk of accumulating multiple NNRTI resistance mutations and developing cross-resistance to next-generation agents. Finally, studies of etravirine have underscored the importance of having an adequate background regimen when using any new and potentially active drug.

Facial Reconstruction Options in the Us- Sept 2007

These are some contacts

Silikon 1000 : http://www.derekjones.com or www.resderm.com or http://www.orentreich.com/ (use off label in the US)

Bioalcamid in Canada (several cities) http://www.faceforward.ca/ or Mexico (monterrey)
egarzaskin@yahoo.com (not FDA approved in the US yet)

PMMA in Mexico (tijuana) luis_casavantes@msn.com ( product approved in the US: Artefill, but very expensive!)

Sculptra : http://sculptra.com/US/Index.jsp (FDA approved for HIV lipoatrophy)

Radiesse: radiesse.com (FDA approved for HIV lipoatrophy)

Helpful Links

http://www.atdn.org/ – AIDS treatment Data Network (ARDN)
http://www.aidsmap.com – Information on HIV and AIDS
http://www.acria.org/treatment/treatment_edu_forumnov800.html – ARCIA (AIDS Community Research Initiative of America)
http://www.facialwasting.org – Useful information about facial wasting and facial wasting treatments
http://www.projinf.org/fs/lipo.html – Comprehensive information about lipodystrophy syndrome
http://www.sculptra.com – Information about the facial wasting facial filler SCULPTRA™ (also known in Europe as New-Fill or in the US as Nu-Fill)
http://www.bioforminc.com/US/radiesse/products.htm – Information about the facial filler Radiesse™ (formerly knows as Radiance™)
http://www.restylane.com/ – Information about the facial filler Restylane®

http://www.perlane-information.com/ – Website about the facial filler Perlane®

http://www.csa.za.org – Center for the study of AIDS

http://www.thebody.com/treat/facial_wasting.html – Articles on facial wasting treatments

Health Insurance Resources for HIV Positive People (non ADAP)

The Georgetown University Health Policy Institute has written A CONSUMER GUIDE FOR GETTING AND KEEPING HEALTH INSURANCE for each state and the District of Columbia — fifty-one in all. These Consumer Guides are available at this web site and will be updated periodically as changes in federal and state policy warrant.

http://healthinsuranceinfo.net/

I hear this broker may find you an insurance policy under HIPPA is you are losing your insurance (you have 61 days to switch otherwise you will be limited by pre-existing conditions)

http://www.ehealthinsurance.com/

Also, president Clinton passed a bill to require high risk pools in different states, but some states like Georgia and Florida decided not to join. Here are the states that provide health insurance to people with pre-existing conditions:

States That Have Risk Pools:
Alabama (for portability only)
Alabama Health Insurance Plan
Phone 1-800-513-1384 or (334) 353-8924

Alaska
Alaska Comprehensive Health Insurance Association
Phone 1-800-467-8725 or (907) 269-7900

Arkansas
Arkansas Comprehensive Health Insurance Pool
Phone 1-800-285-6477

California
California Major Risk Medical Insurance Program
Phone 1-800-289-6574 or (916) 324-4695

Colorado
CoverColorado
Phone (303) 863-1960

Connecticut
Connecticut Health Reinsurance Association
Phone 1-800-842-0004

Florida (not open for new enrollees)
Phone (850) 309-1200

Idaho
Idaho Individual High Risk Reinsurance Pool

Illinois
Illinois Comprehensive Health Insurance Plan
Phone 1-800-367-6410 or (217) 782-6333

Indiana
Indiana Comprehensive Health Association
Phone 1-800-552-7921 or (317) 614-2000

Iowa
Iowa Comprehensive Health Association
Phone (877) 793-6880

Kansas
Kansas Health Insurance Association
Phone 1-800-290-1366 or (316) 792-1779

Kentucky
Kentucky Access
Phone (866) 405-6145

Louisiana
Louisiana Health Insurance Association
Phone 1-800-736-0947 or (504) 926-6245

Maryland
Maryland Health Insurance Plan
Phone (888) 444-9016

Minnesota
Minnesota Comprehensive Health Association
Phone (952) 593-9609

Mississippi
Mississippi Comprehensive Health Insurance Risk Pool
Phone (601) 362-0799

Missouri
Missouri Health Insurance Pool
Phone 1-800-843-6447 (All but NW Missouri)
Phone 1-800-645-8346 (NW Missouri)

Montana
Montana Comprehensive Health Insurance Association
Phone (406) 444-8200

Nebraska
Nebraska Comprehensive Health Association
Phone (402) 343-3574 or (877) 348-4304

New Hampshire
New Hampshire Health Plan
Phone (800) 578-3272

New Mexico
New Mexico Medical Insurance Pool
Phone (505) 622-4711

North Dakota
Comprehensive Health Association Of North Dakota
Phone 1-800-737-0016 or (701) 282-1235

Oklahoma
Oklahoma Health Insurance High Risk Pool
Phone 1-800-255-6065 or (913) 362-0040

Oregon
Oregon Medical Insurance Pool
Phone (503) 373-1692

South Carolina
South Carolina Health Insurance Pool
Phone 1-800-868-2500, ext. 42757, or 1-803-788-0500,
ext. 42757

South Dakota
South Dakota Risk Pool

Tennessee
TennCare Program
Contact Tennessee area county medical assistance offices, or
Phone (615) 741-8642

Texas
Texas Health Insurance Risk Pool
Phone 1-888-398-3927

Utah
Utah Comprehensive Health Insurance Pool
Phone 1-800-705-9173 or (801) 442-6660

Washington
Washington State Health Insurance Pool
Phone 1-800-877-5187

West Virginia
AccessWV
Phone 1-866-445-8491

Wisconsin
Wisconsin Health Insurance Risk Sharing Plan
Phone (608) 441-5777

Wyoming
Wyoming Health Insurance Pool
Phone (307) 634-1393

The New Wave of HIV Drugs is Here

The New Wave of HIV Drugs is Here

For the first time in 10 years, HIV+ patients will have access to two new HIV drug classes. Patients with ongoing viral replication that have been failing current medicines will have a “second chance” to control their HIV by starting new drugs to which their virus has not mutated and become resistant. It is estimated that 20 % of the half a million patients taking HIV medications in the US are not responding to their meds and have ongoing viral replication in their bodies that may shorten their life spans and also make them more infectious to others.

No single HIV medication can control HIV by itself, needing at least two more in combination. But many people have HIV that has developed multidrug resistance (MDR) by mutating around medicines, which allows the virus to aggressively kill the CD4 cells that “direct” the immune system’s response against invaders. MDR patients need to start at least 2-3 “active” drugs that their virus has never seen, but most have not had that luxury in the past few years due to drug approvals that did not happen cocurrently. Fortunately, two new drugs that work in completely new ways are making this possibility a reality for the first time since protease inhibitors were introduced to the market 10 years ago. A new entry inhibitor (Maraviroc , trade name: Selzentry) that works at attempting to block the attachment of HIV to the CD4 T cell, and the first integrase inhibitor (Raltegravir, trade name: Isentress) that works inside the nucleus of the CD4 cell, provide effective new targets to attack the virus. The most critical thing right now is to educate physicians and patients on how to best use these new drugs so that their benefits at lowering viral load to undetectable levels are sustained until a cure is found. Other medications like Fuzeon ( an approved fusion inhibitor), Aptivus and Prezista ( approved second generation protease inhibitors), and TMC 125 ( a second generation non nucleoside analog in expanded access) can be combined with the two novel agents approved this year to hit the virus in different parts of its life cycle outside and inside the CD4 cell.

“I recently started Raltegravir with two other active medicines and my viral load has become undectable for the first time in many years”, said Sharon Braiteh of Houston.” I just pray that my viral load is controlled for a long time so that my immune system can be restored for my body to fight my current cancer and infections”, added Braiteh.

“This is the second wave of HAART (highly active antiretroviral therapy) that will save a lot of lives”, said long term survivor , activist and educator Nelson Vergel. ” I urge patients not to screw up this last chance to get an effective combination before we go through another dry period of no new drugs in the coming few years…It is imperative to do your homework before jumping into a new regimen with limited data”, added Vergel.

Nelson Vergel will be giving the last update for this year on recent conferences that had new data on these and other emerging options for HIV treatment. His lecture will be held on

Monday, September 17

Grady Infectious Disease Program

341 Ponce de Leon Ave

Atlanta, GA 30308

Advance Reservations are required.

Register by calling Positive Impact at 404-589-9040

You may also e-mail:

training@PositiveImpact-atl.org

More information on new HIV medications can be found at Nelson’s web site www.SalvageTherapies.org

When You Have to Fire Your Doctor

Positively Aware July/August 2007
You’re Fired!
Changing your doctor

by Matt Sharp

Donald Trump’s irritating voice rang in my ears as I stormed home from one of the most humiliating experiences as a “patient” in my 20 years of receiving HIV care. The details of the situation are not as important as the light bulb that went off in my head to rectify the situation.

The light bulb told me it was time to fire my doctor! I asked myself, “Do I really want to go through the hassle of finding and transitioning to a new provider?” Everything was going okay until I realized that I may have been getting a little too cozy and comfortable with him. I also wasn’t getting the complete care I needed, but only casual and acute care. After a sleepless night, I finally came to the decision that the time was right for making a change, especially given that this particular ordeal was the catalyst for the termination of my doctor. Firing your doctor can be traumatic!

Read more here:

http://tpan.com/publications/pa/07_04/get_sharp.shtml

Should pharmaceutical employees be allowed to lecture about their products?

I am seeing a very strong trend of allowing pharmaceutical employees to speak to clinician and patient groups about their products in lectures set up by industry. I have attended many CME based and non CME lectures and I can say that I have hardly seen a neutral or unbiased lecture when a pharma employee delivers the message. What happened with allowing private investigators from medical schools, private practice and the public sector to speak instead?

I think it is time to put an end to this trend. The FDA should monitor this behavior and mandate that companies use neutral third parties to deliver treatment information to clinicians and patients.

It would be nice to see all pharmaceutical companies donate money to a large educational entity from medical schools or other venues so that a conglomerate of funding is placed in a pool that would be used for setting up educational programs for clinicians and patients. This entity would be audited yearly by an ethics and content review panel so that information is kept unbiased and all useful public domain information is provided to people who would benefit from it without selectively choosing what data sets to use to drive a message.

I know this is possible!