treatment, and comorbidities compared to younger people. Researchers and treating clinicians may need to consider differentiating between those recently infected at an older age and those who were infected at a younger age and have grown older with the disease due to improvements in therapy (Stoff et al., 2004). Older adults may be diagnosed later in disease progression, as many age-related illnesses can mimic HIV-associated symptoms (Kirk and Goetz, 2009).
In the beginning of the epidemic, researchers and clinicians struggled to understand the nature of the immune defect and the identity of the causative agent. With the discovery of HIV as the causative agent of AIDS, work proceeded rapidly to identify and develop inhibitors of critical steps in the viral life cycle (see Figure 2-1). In 1987, monotherapy with the nucleoside analogue zidovudine (ZDV, also known as azidothymidine [AZT]) became the first licensed treatment for patients with AIDS. Although this treatment saved lives, its effects were relatively short lived because the virus was able to develop resistance to the single agent. The licensure of ZDV was rapidly followed by the development of a series of additional nucleoside analogues, followed by the introduction of nonnucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, entry inhibitors, and integrase inhibitors.
Used in combination, these drugs lead to substantial suppression of HIV replication for extended periods of time. Despite this success, these drugs are not able to eradicate the virus and patients currently must remain on therapy for the remainder of their lives. Even brief lapses in therapy can lead to increases in viral replication and subsequent immune system and other end organ damage.
The overall goal of combination antiretroviral therapy (also known as highly active antiretroviral therapy or HAART) is to limit the ability of the virus to replicate and thus limit its ability to damage the host. Following the widespread use of combination antiretroviral therapy in the United States in the mid-1990s, the mortality rate due to AIDS declined steeply (see Figure 2-2). Continued success in the future will depend to a large extent on the ability to engage HIV-infected persons in care early in the course of their infection and to support them in adhering to treatment regimens. Successful treatment regimens begin with early diagnosis of HIV infection. Research has shown that patients have better outcomes when they begin combination antiretroviral therapy regimens before their CD4 counts decline to fewer than 350 cells/mm3, compared to patients who begin treatment at a more advanced stage of disease (Egger et al., 2002). A broader discussion of CD4 count and prognosis is included in Chapter 3.