New Information on Opportunistic Infections and Co-Infections
Many reports have shown fewer opportunistic infections (OIs) and deaths since the wide-scale availability and use of potent anti-HIV therapy. Also, there have been many reports of people stopping preventive therapies for OIs. Now several studies further confirm that it may be safe for some people to stop preventive therapies when their CD4+ cell count increases are sustained over time. In addition, ongoing research into hepatitis co-infection (with HIV) is beginning to show progress.
Despite success in these areas, there also appear to be increases in the rate of certain AIDS-related cancers. Moreover, a major hospital is beginning to document new increases in the rates of OIs.
Stopping MAC PreventionAn AIDS Clinical Trial Group (ACTG) study examined the safety of stopping MAC (Mycobacterium avium complex) preventive therapy in people who had significant increases in their CD4+ cell count from highly active antiretroviral therapy (HAART). The study enrolled 643 people on MAC preventive therapy who at one time had CD4+ cell counts below 50 but had over 100 cells at the start of the study.
Volunteers were either continued their current MAC preventive therapy, azithromycin (Zithromax®, 1,200 mg once a week) or switched to a placebo. About 60% of them had good control of HIV with HIV RNA below 500 copies.
After over a year, only two people got MAC, both of whom took the placebo. These results imply that it's safe to stop MAC preventive drugs for people whose CD4+ cell counts increase to and remain over 100. If you wish to consider stopping your MAC preventive therapy, discuss it with your doctor.
Stopping PCP PreventionA Spanish study evaluated the safety of stopping PCP (Pneumocystis carinii pneumonia) preventive therapy. Almost 500 people with a history of CD4+ cell counts around 100 participated.
At the start, all volunteers had CD4+ cell counts over 200, HIV RNA below 5,000 copies and were using HAART for at least three months. About 20% had been previously diagnosed with PCP.
Volunteers either continued PCP preventive therapy or received no preventive drugs. After almost a year, not a single case of PCP was diagnosed.
These results suggest that it's possible for people to stop PCP preventive therapy if they have sustained CD4+ cell count increases over 200 and stay on potent anti-HIV drugs that optimally control HIV.
An early report from a similar study, ACTG 888, appears to confirm these results. No cases of PCP have yet been reported in the 252 participants to date.
The federal guidelines for the treating opportunistic infections suggest that it's possible for people to stop primary PCP preventive therapy (to prevent first PCP infection) if they have sustained CD4+ cell counts over 200. However, the guidelines do not recommend that people stop secondary preventive or maintenance therapy (to prevent PCP from coming back). If you consider changing your PCP preventive therapy, talk to your doctor.
Advances in Hepatitis C Virus TherapyThere is possible good news for people with hepatitis C virus (HCV). Results from a small study of peg-interferon (Pegasys, a new formulation of interferon-alfa) suggest that it's far more effective in treating HCV than the current formula of interferon-alfa. The new formulation was compared to standard interferon-alfa in 271 people with cirrhosis of the liver due to HCV. Cirrhosis is a permanent scarring of the liver and indicates a decrease in the amount of functioning liver tissue. Furthermore, the scarring interferes with the normal flow of blood through the liver and results in poor liver function.
The new version of interferon-alfa is bound to polyethylene glycol, which helps the interferon to remain stable and active in the blood for longer periods than standard interferon.
In the study, people received 48 weeks of anti-HCV therapy with a follow-up period of 24 weeks when they did not take any therapy. They received either 90 micrograms (mcg) or 180 mcg of peg-interferon once a week or three million international units of interferon-alfa three times a week. Both formulas required injections under the skin.
Results showed that at 72 weeks, 29% of the participants receiving peg-interferon had undetectable blood levels of HCV compared to only 6% using standard interferon-alfa. Side effects were similar between the two formulas and included headaches, fatigue, flu-like symptoms, nausea, vomiting, depression, fever and chills.
In truth, neither of these success rates are overly impressive. Optimally, even the peg version of interferon may need to be used in combination therapy approach. Another study is ongoing in people who have both HIV and HCV to determine the effectiveness of peg-interferon combined with ribavirin (Rebetol®). Ribavirin combined with a standard form of interferon is called Rebetron® and is generally considered the current standard for treating HCV. Also, HCV advocacy groups including Project Inform are working with Hoffman-La Roche, the developers of peg-interferon, in designing studies that include complementary therapies. The new studies would determine if these therapies (such as milk thistle, coenzyme Q10 and vitamin B12) really benefit people with HCV infection.
AIDS-Related Cancer on the Rise?Recently, the large EuroSIDA study highlighted the increasing rate of non-Hodgkins lymphoma (NHL), an AIDS-related cancer. The study enrolled over 7,000 people in Europe since 1994. While the overall rate of opportunistic infections has declined dramatically, the incidence of NHL has increased substantially.
It's not entirely clear why this is occurring. But one theory explains this may be a result of people living longer or that NHL was seen less frequently in the time before protease inhibitors because people died of other conditions before developing NHL. Immune restoration (increases in CD4+ cell counts) among people on HAART seemingly has little or no impact on NHL. Some researchers wonder if the extensive use of anti-HIV drugs might be contributing to the increase, but there is no clear evidence that this is the case.
Are OI Rates on the Rise?One alarming trend observed over the past 18 months at the San Francisco General Hospital (SFGH) is the rising numbers of OIs. In 1997 cases of PCP, MAC, cytomegalovirus, and cryptococcal disease (a fungal infection primarily of the brain) fell to an all-time low. However, by 1998 the number of these infections diagnosed at SFGH grew above 1997 levels. The 1999 numbers are expected to be even higher.
Earlier HIV testing and better access to treatment and care may have prevented many of these infections. It's been noted that what happens in San Francisco usually happens in the rest of the country a year or two later. So, returns in rates of new AIDS-related infections may be expected over the coming years.
ConclusionWe now have some clear data on the safety of stopping preventive therapy. However, the more worrying issue is the apparent increase in the number of OIs. This clearly indicates the need for newer and more potent anti-HIV therapies, as well as more effective efforts to get people into testing and treatment programs in earlier stages of HIV infection. It also indicates the need for better third line therapies so that we do not return to the situation in which we were in 1996.
This article was provided by Project Inform. It is a part of the publication Project Inform Perspective. Visit Project Inform's website to find out more about their activities, publications and services.