1998

PI Perspective 25 -- September 1998

The 12^th International Conference on AIDS, while a useful and important meeting, not only failed to live up to its theme of "Bridging the Gap," but perhaps inadvertently served to demonstrate how wide the chasm truly is between the have's and the have not's when it comes to AIDS.

Antiviral Update

Over the past few years, research has focused on optimizing the use of protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTIs) in combination with the nucleoside analogue reverse transcriptase inhibitors (NARTIs).

Effect of Combination Therapies on Pregnant Women and Their Children: A small study looking at the safety of anti-HIV therapy use in pregnant women and their newborn children revealed an unexpectedly high number of premature births as well as side effects in pregnant women using anti-HIV therapy with or without a protease inhibitor.
Salvage Therapy Studies: Salvage therapy refers to regimens which are used or being studied for people who have failed one or more protease inhibitor-containing regimens. In this instance,
Combivir^® Alert!: A man was taking a two-drug combination of AZT (zidovudine, Retrovir®) and 3TC (lamivudine, Epivir®). He and his doctor began seeing a trend of increases in his viral load and decreases in his CD4+ cell count.

New Drugs in Development

Overall, the pipeline for truly new drugs is not well filled. While a modest number of new agents are working their way through the development system, only a small portion of them is likely to help people who have failed earlier therapies.

Adefovir Warning: People taking the anti-HIV drug adefovir (Preveon®) for more than 20 weeks may be at higher risk for developing kidney toxicity due to accumulation of the drug in their blood, according to preliminary observations. Adefovir is a new type of reverse transcriptase inhibitor--called a nucleotide reverse transcriptase inhibitor--that is in large studies.
Expanded Access Programs: Three new drugs are currently available in expanded access programs—abacavir (Ziagen®, formerly GW1592), adefovir (Preveon®, formerly bis-POM PMEA) and efavirenz (Sustiva®, formerly DMP266). A fourth drug, amprenavir (Agenerase®, 141W94), is likely to be available soon.

Geno- and Phenotypic Resistance Tests

Despite the recent advances with anti-HIV therapies, some people who are taking anti-HIV therapies are experiencing returns of measurable viral load and/or increases in their viral load (HIV RNA levels) measurements.

Therapy Side Effects Update

Some of the enthusiasm over protease inhibitors has been dampened by reports of a redistribution of body fat (lipodystrophy) that has been observed in some people who have been on long-term protease inhibitor therapy.

Ritonavir Alert: Abbott Laboratories announced they are experiencing manufacturing difficulties with ritonavir (Norvir®) capsules. The production difficulties apply only to the capsules and do not apply to the ritonavir oral solution. The concern that prompted the announcement is the development of a crystalline structure during production of the capsules.

Women at the Conference

While the recent 12^th World AIDS Conference in Geneva provided no real surprises for women living with HIV, the conference surged forward by having numerous sessions specifically dedicated to the treatment and care of HIV+ women.

Opportunistic Infections Update

There has been a dramatic decrease in cases of opportunistic infections (OIs) since the introduction of Highly Active Antiretroviral Therapy (HAART). However, perhaps as a consequence, there are few new therapies in development for the treatment or prevention of opportunistic infections.

Nerve Growth Factor for Peripheral Neuropathy: Interim results from a study of nerve growth factor (NGF) shows that the drug may be an effective treatment for people with peripheral neuropathy. People who received NGF had significantly lower pain scores—from tests which were self-administered—with the group receiving the higher dose having the best results.

Treatment of Gynecological Conditions in Women

Research has shown that higher doses of standard treatments for some gynecologic complications may be required in women with HIV compared to doses required for treating the same conditions in HIV-negative women.

Effect of HAART on HPV: Results from a study of 40 people with HIV showed that highly active antiretroviral therapy (HAART) could help reduce recurrence of genital warts after surgical treatment. Genital warts, like cervical and anal cancers, are a result of infection by human papillomavirus (HPV).

Transmission of Resistant HIV

Researchers at the University of California have published the first evidence of the transmission of multi-drug resistant virus from an HIV-positive person to a person previously uninfected. Although the potential for such transmission has long been known, this case report presents the first hard evidence that such transmission of virus resistant to multiple drugs not only can occur but also does.

Sildenafil (Viagra®) Drug Interactions: The recently approved drug, sildenafil citrate (Viagra®), for erectile dysfunction (impotence) should not be used by people who are using organic nitrates in any form, including 'poppers' and certain drugs taken to decrease high blood pressure.

Antivirals and Children

New studies have begun opening the doors for broadening therapeutic options for children with HIV. Only six drugs [AZT (zidovudine, Retrovir^®), ddI (didanosine, Videx^®), d4T (stavudine, Zerit^®), 3TC (lamivudine . . . .

Federal Guidelines: The recently updated Federal Guidelines for the treatment of children with HIV recommend that infants and children receive combinations that include two nucleoside analogues and a protease inhibitor, and that adolescents be treated based on adult guidelines.

Immune Based Therapy Update

The major focus of immune-based therapy presentations at this year's World AIDS Conference was new information on the use of interleukin-2 (IL-2). Just a day before the conference an international steering committee met to put the finishing touches on plans for a large international study of IL-2 which will enroll 4,000 volunteers at over 200 sites worldwide.

Prevention of Mother-to-Child HIV Transmission

The prevention of HIV transmission from mother-to-child (also called vertical or perinatal transmission) garnered much attention at the recent 12th World AIDS Conference. Promising data continued to show that anti-HIV therapy and other important prenatal (before birth) and postnatal (after the birth, early infancy) health care tools can significantly reduce HIV transmission to newborns.

Report from the Seventh Immune Restoration Think Tank

The seventh meeting of the Immune Restoration Think Tank: The Dobson Project took place in San Francisco in March 1998. The theme of the meeting was `Back to Basics' and emphasized basic research questions that must be revisited in light of new information about the immunologic consequences of highly active antiviral therapy (HAART).

PI Perspective 24 -- April 1998

Report from the Great Chicago Plateau

The 5^th Conference on Retroviruses and Opportunistic Infections, held in Chicago in the first week of February, heralded few breakthroughs or surprises. Instead, it painted a picture of slow but steady progress following the advances seen with the advent of protease inhibitors and triple combination therapy beginning in 1996.

Antiviral Updates

New results from studies offer people more information on how to use currently available drugs. It may be possible to use simplified dosing regimens which will make the drugs far easier to take and also likely to increase adherence.

Indinavir in Women: Little is known about the effects of hormones on the metabolism, potential effectiveness or side effects of drugs in women. A small study looking at the effects of the menstrual cycle on indinavir (Crixivan©) levels in the blood found dramatic differences in time to peak level and time to optimal therapeutic levels based on the various phases of the menstrual cycle over the course of a month.

Double Protease Inhibitor Combinations

Dual protease combinations are of interest because some combinations offer the prospect of reducing the dose and dose frequency of the drugs compared to what is required when they are combined with the nucleoside analogue reverse transcriptase inhibitor (NARTI) drugs (such as AZT, ddI, ddC, d4T and 3TC).

Eradication - Dead or Alive, or Even Necessary?

Because the concept of HIV eradication was new and sounded so exciting when first introduced two years ago, it was treated with great fanfare in the popular and community press. Eradication efforts were aimed only at people who were able to begin aggressive antiviral therapy

Protease Paunch or "Buffalo Hump"

While there have been many reports of lipodystrophy (changes in fat distribution) after long-term protease inhibitor therapy, so far, there are no widely accepted explanations of its cause.

Lower Dose Maintenance Therapy

Two recent studies asked whether it is possible to switch to a "less potent" maintenance anti-HIV regimen after sustaining HIV RNA levels below 200 copies for at least 2 months. The hope would be that once initial HIV RNA levels are brought under control, "maintaining" viral suppression with a less potent antiviral approach could offer the potential to decrease the complexity of regimens that people are taking for the long-term.

Drug Identification Chart

Drug Identification Chart: Protease Inhibitors, NARTIs (Nucleoside Analogue Reverse Transcriptase Inhibitors), and NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors).

New Drugs on The Horizon

Recent advances in anti-HIV treatment have primarily come not from new therapies but from better understanding in how to use existing drugs, such as new combinations and simplified dosing regimens.

Interleukin 2 (IL-2)

Several studies confirmed the ability of interleukin-2 (IL-2, Proleukin©) to induce substantial CD4+ cell increases in HIV-infected people receiving antiviral therapy. Conflicting reports remain regarding the ability of IL-2 to effect changes in the rate of clearance of HIV, particularly HIV lurking in quiet reservoirs.

Hydroxyurea - New Observations

Using drugs that inhibit HIV in different ways, and at different places in the virus' reproductive cycle may be important to maximally suppress HIV replication. Hydroxyurea appears to work against the virus differently than the currently available anti-HIV drugs, and thus it is particularly interesting.

Self-Controlled HIV Prevention?

For women who have been following the development of microbicides for self-controlled methods to prevent infection from HIV and other sexually transmitted diseases, data were reported on PRO 2000 Gel, a virucidal (kills the virus) topical gel that does not appear to significantly disrupt or inflame the cells of the vaginal tract.

Update Opportunistic Infections

The overall incidence of opportunistic infections (OIs) has significantly decreased since the availability of highly active antiretroviral therapy (HAART). While there is evidence that HAART results in significant and clinically relevant immune recovery in many people, it is not immediate and not complete.

Cervical Cancer and Viral Load

Several studies looking at the role of HIV viral load as a predictor for disease progression and death have recently been reported. These studies confirm that high viral load is a predictor for disease progression. One study focused on the role of viral load in predicting an increased risk of pre-cancerous or cancerous cervical abnormalities.

Hepatitis in HIV Diseases

Liver problems are a frequent cause of disease and sometimes death in people with HIV. Technically, any significant irritation or inflammation of the liver is called "hepatitis," but the term is more commonly used to refer to several infections of the liver.

HIV and the Genital Tract: The presence of HIV in the genital tract has been previously reported, with several studies showing that reductions in viral load in this compartment correlate with decreases in blood for individuals on highly active antiretroviral therapy (HAART).
AZT and Mother to Child Transmission: The reduction in HIV transmission from mother-to-infant with the use of anti-HIV drugs has been a remarkable success story.

Progressive Multifocal Leukoencephalopathy (PML)

PML is a rare AIDS-related condition, caused by the JC Virus. Between 80 to 85% of all adults, world wide, are exposed to this virus at some time in their lives, but it only appears to cause disease in people with a weakened immune system.

This information is designed to support, not replace, the relationship that exists between you and your doctor.
©1998. ÆGIS.