Should ART be deferred in patients at risk for nonadherence?
Since nonadherence to antiretroviral therapy (ART) may hasten the development of resistance, it may seem reasonable to defer ART in HIV-infected patients who have risk factors for nonadherence, such as substance abuse. However, Braithwaite and associates1 report that even patients with suboptimal adherence can benefit from earlier initiation of ART. They used a computer simulation of HIV disease progression to evaluate alternative treatment thresholds. This tool had the ability to weigh the benefits of earlier initiation of therapy, such as reduced mortality, against the disadvantages, such as the development of resistance mutations (and the resulting limitation in future drug options) and increased exposure to toxicity. The simulation model was designed to assign otherwise similar patient cohorts to different treatment decisions and compare the effects of these decisions on outcome.
Earlier treatment was associated with increased life expectancy across a broad range of adherence rates. Starting therapy at a CD4+ cell count of 500/µL improved life-years and quality-adjusted life-years (QALYs) compared with starting therapy at CD4+ cell counts of 350/µL or 200/µL, regardless of adherence. With 100% adherence, early therapy was associated with as much as 3.7 additional life-years and 3.3 additional QALYs. With 50% adherence, earlier therapy conferred an additional 7.4 life-years and 6.7 additional QALYs. The authors acknowledge that treatment adherence is still important, and they emphasize the need for close monitoring and interventions to improve adherence in high-risk patients.
How much does directly administered ART affect virological outcome?
Although directly administered ART (DAART) has been shown to be beneficial in HIV-infected drug users, a recent study found that the persistence of DAART after self-administered therapy (SAT) did not improve virological outcomes in this population.2 Maru and colleagues2 studied 141 HIV-infected drug users who received 6 months of DAART or SAT. Virological success was defined as either an HIV-1 RNA level of less than 400 copies/mL or a 1.0 log10 reduction from baseline. After 6 months of therapy, the 2 groups did not differ in virological success (58% in the DAART group and 56.7% in the SAT group). They also did not differ in mean reduction in log10 HIV-1 RNA level or mean change in CD4 count.
A high level of social support was the only significant predictor of virological success. The authors say that this finding suggests the need for integrated interventions that address complicated social issues. Also, the provision of co-located medical and case management services may be a particularly important component of DAART.
While virological benefit did not persist beyond the intervention, DAART is still an effective way to improve adherence among drug users. Potential ways to improve long-term outcomes include extending the duration of the intervention, providing some form of “booster” DAART when nonadherence is a problem, and developing more effective transitions from DAART.
Assessing the causes of race and sex differences in AIDS-related mortality
Studies have consistently shown that in the United States, the long-term survival rate is lower in blacks with AIDS than it is in nonblacks with AIDS. According to a study by Lemly and associates,3 disparities in the use of highly active ART (HAART) are a major factor in the race-associated differences in mortality. In contrast, differences in the use of HAART do not appear to account for the increased AIDS-related mortality observed in women.
The investigators studied 2605 HIV-infected patients, 38% of whom were black and 24% of whom were female. Compared with nonblack patients, black patients presented with more advanced HIV disease and were less likely to receive HAART while in care. Compared with men, women presented at earlier stages of HIV disease and were less likely to receive HAART. The percentage of time in care while receiving HAART was 47% in blacks compared with 76% in nonblacks, and it was 57% in women compared with 71% in men. After adjustment for baseline characteristics, mortality was associated with black race, female sex, older age, lower CD4 count, higher HIV-1 RNA level, and injection drug use. After adjustment for the duration of HAART, black race was no longer associated with increased mortality; however, female sex remained a significant risk factor for death.
1. Braithwaite RS, Roberts MS, Goetz MB, et al. Do benefits of earlier antiretroviral treatment initiation outweigh harms for individuals at risk for poor adherence? Clin Infect Dis. 2009;48:822-826.
2. Maru DS, Bruce RD, Walton M, et al. Persistence of virological benefits following directly administered antiretroviral therapy among drug users: results from a randomized controlled trial. J Acquir Immune Defic Syndr. 2009;50:176-181.
3. Lemly DC, Shepherd BE, Hulgan T, et al. Race and sex differences in antiretroviral therapy use and mortality among HIV-infected persons in care. J Infect Dis. 2009;199:991-998.