An 8-year study of almost 2500 people in a Swiss HIV group found that people who interrupted antiretroviral therapy gained fewer CD4 cells and ran a higher risk of new AIDS diseases and death than people who took their antiretrovirals regularly.1
The strong antiretroviral combinations available today help people avoid AIDS diseases and live longer, healthier lives with HIV. Compared with older antiretroviral combinations, newer triple-drug therapies have fewer side effects and are easier to take. Still, many people interrupt their antiretroviral treatment, sometimes without the knowledge of their HIV doctor.
Several trials compared structured antiretroviral breaks with steady therapy in people with HIV.2-4 In all these studies, people in the antiretroviral-interruption group stopped treatment if their CD4 count rose to a certain level, then restarted treatment if their CD4 count fell to a certain level. All studies found higher rates of new HIV diseases -- and sometimes non-HIV diseases -- in people who interrupted antiretroviral therapy than in those who never stopped taking their drugs.
Trials like these provide strong evidence that interrupting antiretroviral therapy has more risks than benefits. But these trials ran for only a few years. A large, ongoing HIV population study like the Swiss HIV Cohort Study can offer further insight into the impact of antiretroviral interruptions over a much longer period. With that goal in mind, researchers planned this analysis of the Swiss HIV Cohort Study.
The Swiss researchers determined the proportion of people in each group who reached a CD4 count above 350 or above 500 during the study period. They also recorded rates of new AIDS diseases and death. Then the researchers used a standard statistical method to pinpoint predictors of failure to reach a CD4 count above 350 or 500. The factors they considered in this analysis were study group (A, B, or C), gender, age, duration of HIV infection, previous treatment with fewer than three antiretrovirals, intravenous drug use, hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, Centers for Disease Control and Prevention (CDC) stage C HIV disease (that is, an AIDS-defining disease), the year antiretroviral therapy began, and viral load, CD4 count, and CD8 count when starting triple therapy.
Observation time of study participants averaged 7.1 years. Half of the study group (51%) interrupted antiretroviral therapy at least once. For the whole study group, the median CD4 count rose from 210 to 491 in 8 years. People who interrupted treatment gained a median of 133 CD4 cells through 8 years, compared with 360 CD4s in group B and 395 in group C. Much higher proportions of people in groups B and C than in group A reached a CD4 count above 350 or above 500 during the study period (Table 1). Statistical analysis showed that the longer the antiretroviral interruption, the smaller the CD4 gain.
Table 1. Proportions of Study Group Members Reaching a CD4 Count Above 350 or 500 in 8 Years
|Study group*||Reached CD4 count above 350||Reached CD4 count above 500|
|*See How the study worked for group definitions.|
Further statistical analysis identified several factors that raised or lowered the chance of reaching a CD4 count above 350 or 500, regardless of what other risk factors a person had:
Predictors of reaching a CD4 count above 350:
Predictors of reaching of CD4 count above 500:
The overall rate of new CDC stage B diseases (relatively minor diseases like yeast infection and herpes zoster) was 11.9 per 1000 person-years. The rate was much higher in group A (15 per 1000 person-years) than in group B or C (8.1 and 9.2 per 1000 person-years). The overall rate of new CDC stage C diseases (major diseases like non-Hodgkin lymphoma and Pneumocystis pneumonia) was 11.3 per 1000 person-years. The rate was again higher in group A (14.8 per 1000 person-years) than in group B or C (8.1 and 7.4 per 1000 person-years). Rates of new CDC stage C diseases increased as the length of treatment interruption increased: 6% with interruptions less than 1 month, 10.4% with interruptions of 1 to 5 months, 10.7% with interruptions of 6 to 14 months, 13.9% with interruptions of 15 to 31 months, and 13.7% with interruptions longer than 31 months.
Figure 1. The death rate through 8 years of observation in the Swiss HIV Cohort Study was highest among people who interrupted antiretroviral therapy for at least 1 month (group A) and lower in people who did not interrupt treatment but had a viral load above 1000 copies at some point after 6 months of therapy (group B) and in people who did not interrupt treatment and always had a viral load below 1000 copies after 6 months of therapy (group C).
The overall death rate during the 8-year study was 14.3 deaths per 1000 person-years. That rate was twice higher in group A (antiretroviral interrupters) than in group B or C (noninterrupters): 19.6 per 1000 person-years in group A versus 9.7 and 8.2 per 1000 person-years in group B and C (Figure 1). The rate of HIV-related death was also higher in group A (3.9 per 1000 personyears) than in group B or C (3.5 and 2.0 per 1000 person- years).
Over the 8-year study period, people who interrupted their antiretroviral pill taking for a month or more responded to therapy worse than noninterrupters in several important ways:
Sometimes it is necessary for a physician to interrupt a patient's antiretroviral therapy, for example, when some serious non-AIDS diseases develop. But major randomized trials and this Swiss HIV Cohort Study all found that interrupting antiretroviral therapy poses serious risks. You should never stop your antiretrovirals, unless your physician tells you to. If you believe your antiretrovirals are causing side effects you cannot tolerate, you should discuss those problems immediately with your doctor. Some side effects go away on their own after a short time. Or you may be able to switch to other antiretrovirals that are just as strong but do not cause side effects in you.
The study also found that the risk of a new AIDS disease rose as the overall length of treatment interruption increased. Based on that finding, the Swiss team suggests that "if any treatment interruption is required, it should be as short as possible."
Two other important findings emerged from this study: (1) People who started antiretroviral therapy at a higher CD4 count had a much better chance of reaching a CD4 count above 500 through 8 years of treatment, and (2) people who did not interrupt treatment and always had a viral load below 1000 copies after 6 months of therapy had the best overall responses. For these reasons, the Swiss researchers believe their results support starting antiretroviral therapy early in the course of HIV infection, avoiding treatment interruptions, and keeping the viral load as low as possible.