Highly Active Antiretroviral Therapy
The use of a combination of three or more drugs to combat HIV has come to be known as highly active antiretroviral therapy (HAART). Most clinicians commence treatment of HIV/AIDS with a combination of various RT and PI drugs. The availability of new antiretroviral drugs, including drugs in new classes, requires clinicians to constantly update and modify the HAART regimens used to combat HIV. Until recently it was common practice to begin HAART for any HIV-infected person whose CD4 count dropped below 200 or for anyone who manifested symptomatic disease (i. e., infections or cancers associated with HIV/AIDS). However, new data on treatment choices for infected people warranted an update of the International AIDS Society-USA guidelines for HAART. It is now suggested that treatment should be initiated before CD4 count declines to less than 350 (Hammer et al., 2008). The decision regarding when to begin therapy must be tailored to the individual patient based on the potential benefits and risks of early or delayed therapy.
HAART has proven to be an effective treatment regimen for many HIV/AIDS patients. Various studies have demonstrated that, when properly administered, HAART can inhibit HIV replication and frequently can reduce viral load to an undetectable level, improve immune function, and delay progression of the disease.
The excellent clinical results produced by HAART in the early years after it was implemented led to a surge of optimism that this advance in antiretroviral therapy might not only delay HIV/AIDS progression but also ultimately eradicate the virus. Unfortunately, as we will see, these early projections were overly optimistic.
A significant drawback of HAART that influences adherence is drug toxicity. Low compliance is often associated with adverse drug side effects, including anemia; insomnia; mouth ulcers; diarrhea; inflammation of the pancreas; respiratory difficulties; metabolic disturbances; increased cholesterol and triglyceride levels (major risk factors for cardiovascular diseases); gastrointestinal discomfort; liver damage; excess fat accumulation in areas such as the abdomen, upper back, and breasts; fat atrophy in the face, legs, and arms; and skin rashes (Lo et al., 2008; Mosack et al., 2009). These side effects can be so severe that affected people are unable to tolerate HAART. Fortu – I nately, some of the HAART drug combinations introduced in recent years have fewer side effects than previously used combinations, making adherence less of an issue. Researchers have recently detected an f especially troubling condition attributed to HAART called immu – | nosenescence, a form of premature aging of the immune system that may occur among some people on this drug regimen. While the verdict is still out on this possible side effect, there are indications that prolonged use of antiretroviral medications may lead to loss of mental acuity and other age-related issues (Tasker, 2011).
Lack of adherence to HAART because of dosing complexities and/or drug toxicity side effects can lead to less than optimal therapy,
outright treatment failure, and the development of drug-resistant strains of HIV (S. Boyer et al., 2011; Li et al., 2011). Recent improvements in medication dosing schedules (e. g., once or twice a day versus three times a day) and reductions in pill quantity (e. g., combining two or three drugs in one pill) have resulted in better adherence to HAART.
Despite the recent improvement in HAART regimens, evidence indicates that only about 28% of HIV-infected Americans are recipients of HAART treatment that produces optimal reduction in their viral load (Brown, 2011). This low percentage is primarily attributable to a large number of infected people who are unaware of their status or who cannot get or do not want treatment. Fortunately, about 77% of people receiving HAART have a fully suppressed viral load (Brown, 2011).
Another problem with HAART that surfaced in recent years further dampened the optimism and excitement associated with the early years of this treatment protocol. It is now clear that HAART does not eradicate HIV from latent or silent reservoirs in the brain, lymph nodes, intestines, bone marrow, and other tissues, cells, and organs where the virus may reside undetected and intact, even though blood plasma viral loads drop to minimal or undetectable levels (Carter et al., 2010; Fang, 2010; Sigal et al., 2011). Once treatment with the HAART regimen stops or is seriously compromised because a patient is too sick with toxic side effects or too confused by the complexity of dosing regimens, the virus sequestered in these lethal reservoirs typically comes roaring back, or it mutates, resulting in new strains of HIV that are less susceptible to the HAART drugs.
On a more positive note, HAART has been shown to reduce the likelihood of HIV transmission (Cohen et al., 2011; Hammer, 2011; Torian et al., 2011). A recent study indicates that treating HIV-infected people with HAART medications at an early stage of the disease process, when their immune systems are still relatively healthy, can reduce the likelihood of transmitting HIV to an uninfected partner by 96% (National Institute of Allergy and Infectious Diseases, 2011). However, an infected person can transmit the virus at any time after becoming infected, even while undergoing HAART (Shapiro & Ray, 2007). Many infected people transmit HIV to sexual partners before they are aware of their HIV-positive status and prior to beginning treatment.
Has the availability of HAART influenced HIV-negative people to change their sexual behaviors? Do people undergoing this treatment regimen change their sexual behaviors after beginning treatment? Evidence collected in the early years of HAART indicated that at least some HIV-negative gay and bisexual men increased their involvement in risky sex, perhaps because of the availability of this treatment regimen (Dilley et al., 1997; Kelly et al., 1998). More recent studies have confirmed a continuation of this trend toward increased sexual risk taking among gay and bisexual men as a result, at least in part, of improved treatment for HIV/AIDS (Brewer et al., 2006; Oster et al., 2011; Peterson & Bakeman, 2006).
Many persons who are aware that they are infected with HIV do refrain from engaging in risky sexual behavior (Shapiro & Ray, 2007). Two studies—one a 16-state sample of HIV-infected MSM and the other a representative sample of the adult U. S. population in care for HIV/AIDS—found that 31% of the MSM and 32% of the adult respondents in the broader study were engaging in "deliberate abstinence" by refraining from vaginal, anal, or oral intercourse over the previous 6 months to a year (Bogart et al., 2006).