(2003; 211 pages)
Chapter XII - Human immunodeficiency virus and acquired immunodeficiency syndrome
Of those patients suffering from HIV/AIDS, approximately one-third take their medication as prescribed (1). Even when patients fully comprehend the consequences of nonadherence to medications, adherence rates are suboptimal (2,3). Good adherence is a decisive factor in treatment success.
Unlike other chronic diseases, the rapid replication and mutation rate of HIV means that very high levels of adherence (e.g. ≥ 95%) are required to achieve durable suppression of viral load (4 - 6). Recent studies of patients with HIV/AIDS have reported low adherence rates, similar to those seen for other chronic diseases. Suboptimal adherence may rapidly lead to resistance, which can then be transmitted to other people (7 - 10).The potent and effective new combinations of antiretroviral agents, known as highly active antiretroviral therapy (HAART), have proven efficacious in reducing viral load and improving clinical outcomes. However, the large number of medications involved, the complicated dosing requirements, and the suboptimal tolerability make adherence difficult. Because of the great importance of adherence to antiretroviral treatment of HIV, good strategies for maximizing adherence are essential.
There is no doubt that HAART is one of the most celebrated treatment advances in recent medical history. Nucleoside reverse transcriptase inhibitors (usually two) when combined with non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both, are highly effective in reducing viral replication and improving clinical outcomes (11,12). In patients with HIV/AIDS, these multidrug regimens, although remarkably efficacious, result in HIV treatment having the most complicated regimens that have ever been prescribed for conditions requiring continuous open-ended treatment (13).
Many researchers believed initially that HAART would completely eradicate the virus from the host (14,15). However, low levels of viral replication persist in small reservoirs even when viral loads are undetectable. Resting memory T-cells, which harbour proviral DNA, survive for far longer than originally thought (5,6,16 - 18).Therefore, adherence to HAART must be almost perfect to achieve lasting viral suppression. Paterson and colleagues (6) found that adherence at levels less than 95% independently predicted viral resistance, hospital admissions and opportunistic infections. Even among patients who reported adherence rates of ≥ 95%, 22% experienced virologic failure during the study period. In another study, Bangsberg and colleagues (4) found that none of the individuals with adherence greater than 90% progressed to AIDS, whereas 38% and 8% of those with adherence rates ≥ 50% and 51 - 89%, respectively, progressed to AIDS. Missing even a single dose in a 28-day reporting period has been shown to predict treatment failure (5).
Nonadherence to HAART can have important public health implications. Drug resistance can be transmitted to other persons during high-risk activity, which can then limit therapeutic options (7 - 10). Some studies have reported that as many as 80% of isolates from newly infected people are resistant to at least one class of currently approved antiretroviral medications, and that 26% of isolates are resistant to several classes of medication (18). Although these estimates are at the higher end of the spectrum, they nonetheless suggest that transmission of drug-resistant strains is increasing (10).
Because adherence of patients with HIV to antiretroviral medications is essential for both clinical effectiveness and public health, research in this area has burgeoned over the past few years.