Living With HIV, Dying Of Cancer
As we saw in the run-up to this past weekend, World AIDS Day provides a spike in media coverage on an issue whose everyday impact on middle-class North Americans, thanks to medical advances, is virtually nil. But some of those medical advances may have created another threat to those infected with HIV.
In the 25 years or so since the term "acquired immune deficiency syndrome" was coined, HIV-AIDS clinicians and scientists have witnessed a virtually unprecedented transformation in disease management. Most notable is that antiretroviral drugs now enable many individuals who have HIV to survive indefinitely with good quality of life, instead of suffering a rapid disease progression and certain early death. As many have noted, this progress has mostly been achieved in relatively rich Western countries in which access to these lifesaving drugs is assured.
But that new longevity in the Western version of the disease has brought other problems. Clinicians and researchers are seeing, as a result of the progress in life expectancy accomplished through the development of antiretroviral drugs, an underreported and unforeseen consequence of HIV infection: As the New England Journal of Medicine and other publications have reported, people who have been HIV-positive over long periods are presenting in high numbers with a variety of cancers that are both life-threatening and that defy the traditional therapies used to treat cancer in those who do not have HIV. These cancers include lymphomas, carcinomas and lung cancers (in smokers and non-smokers). Although the numbers are still relatively small overall, these cancers are occurring with far higher frequency among HIV-infected people than among members of the general population.
One likely reason is that, above all, HIV infection causes a loss of immunological function that cannot be completely repaired by antiretroviral drugs (ARVs). ARVs combat replication of HIV, which prevents the rapid deterioration of the immune system and helps ensure that HIV patients will not fall prey to pneumonias and other infections that occur most commonly in people with weakened immune systems. However, the HIV patient's immune system may still have been compromised in its ability to defend against cancer.
These observations in cancer incidence raise a number of important concerns. One is whether rates of cancer in HIV-infected populations will continue to rise and whether the cancers will be restricted to certain types or will diversify. Another has to do with treatment: For HIV-infected people, chemotherapy may temporarily preclude the use of ARVs to prevent against drug toxicity or adverse interactions. Interruptions in HIV therapy may lead to renewed replication of the virus and exacerbation of full-blown disease.
Another major concern is that these increased rates of cancer are being discovered mostly among those who have been infected with HIV for five to 15 years. Assuming that our antiretroviral drugs continue to be effective, and possibly become more effective, what does this mean for those who will have been successfully treated for HIV over longer periods, such as 10 to 25 years? Will they be even more susceptible to developing cancer? No one knows yet, but we'll need long-term surveillance of HIV-infected people to track cancer occurrences.
It is possible that the number of cancers seen in HIV-infected people will plateau. Many of those who have been successfully treated with antiretroviral drugs over long periods began therapy with regimens that were both less effective and more toxic than those that are in widespread use today, which may have contributed to current cancer rates.
But widespread damage to the immune system may already have taken place in almost all patients, regardless of when their infections were diagnosed, by the time HIV therapy is initiated; and the body's natural defense mechanisms against cancer may already have been compromised by the time ARV therapy is commenced.
Many people have forgotten that certain rare cancers, such as Kaposi's sarcoma, were recorded in HIV-infected individuals with relatively high frequency in the 1980s, before antiretroviral drugs were available. Then, as now, it was surmised that this increased frequency was attributable to the damage that HIV had inflicted on the immune system.
The new data on cancer underline the need to develop better drugs that will work not just to arrest HIV replication but to restore immune function more effectively than do those drugs that are currently available. The changes they reflect in the evolution of HIV-AIDS as a long-term condition and in the quality of life of those living with it are vivid reminders that AIDS remains a fearsome disease, despite all the progress we've achieved over a quarter-century in therapies, acceptance and awareness.
Mark Wainberg, an AIDS researcher and activist, directs the McGill University AIDS Center at the Montreal Jewish General Hospital. He was co-chairman of the XVI International AIDS Conference in Toronto last year and is a former president of the International AIDS Society.