Recently, a team of Hopkins researchers, in collaboration with researchers from several other institutions, conducted a study to determine how the age of patients impact how their bodies respond to a widely used AIDS drug regimen.
Specifically, the researchers studied the initial HAART regimen class on virological and immunologic response within 24 hours after initiation.
The importance of this project was attributed to the current guidelines that recommend the initiation of HAART using either ritonavir-boosted protease inhibitors or nonnucleoside reverse-trasciptase inhibitors; these guidelines presently do not differentiate by age, although a number of older individuals contributed to the data that informed these guidelines.
Since its emergence in the 1980s, AIDS has been an area of focus for many researchers, physicians and scientists. A cure for the infection has so far eluded scientists; however, a widely used treatment scheme called highly active antiretroviral therapy, or HAART, has been developed.
HAART is the combination of at least three antiretroviral drugs to combat HIV, a retroviral agent. The drugs attack different parts of HIV or stop the virus from entering blood cells. This regimen has varying degrees of success for different people. However, even among people who respond well to HAART, the treatment does not completely eliminate HIV from the host individual’s body — it merely slows down the rate of viral replication.
Because HIV is constantly mutating and finding novel ways to overcome the human body’s efforts to fight the infection with natural immune responses, HAART drugs must constantly be improved to combat new strains of HIV.
In building the optimal environment for HAART to work, HIV specialists and researchers argue that different factors contribute to the success of this therapy, including time of initial treatment and adherence, as well as natural factors such as genetic pre-disposition.
Statistics have shown that the numbers of individuals aged at least 50 years with HIV have been increasing. Some scientists attribute this to better methods of diagnosis than in previous years, while others remain skeptical.
Although it is generally accepted that older HIV-infected individuals initiating HAART will have a decreased immunological response and an increased virological response, meaning a decrease in viral replication, when compared with younger individuals, published data has been mixed. While some studies have reported increased virologic suppression in older compared with younger adults, others have reported either the reverse or no differences.
Drawing from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), a collaboration of eight interval and 13 clinical prospective cohort studies of demographically hetereogeneous HIV-infected adults from the US and Canada, Keri Althoff and her team analyzed the data from 12,196 antiretroviral-naïve adults who initiated HAART between 1998 and 2008 using a boosted protease inhibitor-based regimen or a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen.
The data revealed that no definitive improvement in virologic response in older patients compared with younger age groups existed; when classified by regimen class, in contrast to the virologic outcome, the immunologic outcome was clearly different by age with older individuals less likely to have an increase. However, previous studies had attributed improved virologic response among older adults to better adherence to HAART.
This study provides particularly reliable information due to its large study population of antiretroviral therapy native adults. Additionally, modern analytical methods for the possible selection bias induced by censoring individuals who had discontinued or changed their initial HAART regimen also contributed to the strength of the data from this study.
However, theoretically, older individuals with HIV infection may have had their infection longer than younger individuals, and these differences may have contributed to the age-related effects on immunologic response.
Another limitation was the using of a definition for viral suppression that is higher than current standards. Additionally, there was no direct measurement of adherence, such as drug plasma levels.
This study did not find any conclusively strong evidence of an interaction between age and initial anti-retroviral regimen on virologic and immunologic response to HAART.
However, decreased immunologic response with increasing age may have implications for age-specific when-to-start guidelines.
Although HIV has been largely explored since it first appeared among humans, it is a chronic disease that requires life-long therapy; therefore, optimizing initial HAART regimen is very important.
Although future studies will have to evaluate the impact of toxicity and non-AIDS-related comorbidities on virologic and immunologic outcomes, the current data does not provide substantial enough evidence to justify the use of specific HAART regimen for specific age groups.
However, given the impact of white blood cell count on long-term survival, initiating HAART at higher white blood cell cell counts for older individuals is not a completely irrelevant option considering the decreased likelihood of a robust CD4 cell response with increasing age.
