Participants who started antiretroviral therapy (ART) soon after diagnosis of their HIV status earlier this large study showed no differences in lung function or neuropsychological performance when compared to people entirely randomized to early extended antiretroviral therapy (ART) in According to two studies presented last week at15thEuropean AIDS ConferenceBarcelona, Spain.
Arelated study showed that early treatment the START was associated with a greater loss of bone mass over time.
Start antiretroviral treatment prior to the development of severe damage to the immune system significantly reduces the risk of progression of HIV disease and death, but early treatment can, potentially, also have disadvantages, including increased exposure to the toxicity of antiretroviral drugs. A study called INSIGHT noted that with regard to the study START (strategic distribution of antiretroviral treatment free translationStrategic Timing of Antiretroviral Treatment) Was designed to address the long controversy over the optimal time for treatment of HIV, especially for people who still have high counts of CD4.
The main results of START, thepresented last summer in the Northern Hemisphere at the Conference in Vancouver the International AIDS Society andpublished in August in 27New England Journal of Medicine, Showed that participants randomized to start ART soon after diagnosis of HIV seropositivity had a significantly lower risk of disease and death than those who expected a significant drop in CD4 count. The immediate treatment group not only had a 72% lower risk of AIDS-related infections and cancers also related to AIDS compared to those who postponed the start of ART, but also were 39% less likely to suffer serious events unrelated to AIDS (heart, liver and kidney events and cancers unrelated to AIDS) or death.
The initial project includes several sub-studies looking at the effects of early treatment versus delayed start on specific outcomes known or suspected to be associated with HIV infection or its treatment, including bone density, pulmonary function and cognitive function.
Lung substudy related to the study START
Ken Kunisaki, the University of Minnesota presented lung results since the beginning of the sub-study, which compared the changes in lung function in groups where the HAART scheme is immediate or delayed.
Chronic obstructive pulmonary disease (COPD) is an emerging comorbidity related to HIV infection, recorded Kunisaki, as the background. Observational studies have shown that people with HIV are at risk for COPD, but there are conflicting data on whether the ART be associated with increased risk or not. The underlying mechanisms are unclear and meanwhile, may be related to chronic inflammation, increased risk of pneumonia and other lung infections, as well as changes in pulmonary microbiota and perhaps the action of antiretroviral drugs, he said.
In this substudy, participants had spirometry done online and, thereafter, annually. Spirometry is used to assess lung function by measuring the amount of inhaled and exhaled air. The main outcome measure for this analysis was the change in forced expiratory volume, ie the amount of air a person can breathe in one second (VEF1). VEF1 generally has the ability to peaks around 25 years of age and then decreases over time; a level below 30% of the maximum is considered disabling. The results were stratified by smoking.
This substudy included 518 people randomized to the early group of immediate ART and 508 in the deferred group starting ART. The distribution of participants in the substudy differed from the study as a whole, with about 30% in Africa and Europe, 19% in South America, and about 10% in Asia and the US. About 70% were male and the average age was 36 years. About 60% had never smoked, 28% were smokers and 11% were former smokers.
During a mean follow-up period of 2,0 years, the slope of VEF1 showed "Absolutely no difference" between the arms of the immediate treatment group and delayed start of ART for both smokers and non-smokers, demonstrated Kunisaki.
Among smokers, the VEF1 fell -34 ml / year in the immediate ART group and -31 ml / year in the deferred group, a difference that was not statistically significant (p = 0,83). There was also no significant difference between treatment arms among non-smokers, -29 vs -22 ml / year, respectively (p = 0,56) - though smokers have shown larger declines than non-smokers, in both study arms
Turning to the dificultadade self-reported respitatória with standard lung function the respitarótio questionnaire St George's (SGRQ-C, for its acronym in English), scores decreased - 1,1a for immediate HAART arm and - 0.5 arm deferred among smokers, and fell in - 1,1 0,4 + while rose among non-smokers; no significant difference under a statistical point of view. Looking for specific domains for the symptoms, activity and impact, the only significant difference is that worsened the symptoms reported by smokers in the immediate ART early group (vs -2,9 significant (+ 1,6). Although the changes were small and mostly not significant, it is notable that among non-smokers scores from all three domains of the SGRQ and COPD assembly fell into immediate HAART arm, indicating improvement. - during the ascent in deferred initiation arm "When comparing the immediate start of arms ART vs early deferred ART ART has no impact on decline in lung function "in people living with HIV and who have CD4 counts above 500 cells / mm3, the researchers concluded." The ART Immediate can be offered without the worry of increasing the risk of COPD in these patients. "
Substudy related Neurology
Finally, Richard Price, the University of California, San Francisco, presented the findings on behalf of the sub START child neurology which analyzed the evolution in performance between 592 random participants to start immediate or deferred ART
Participants in the substudy, neuropsychological tests completed with the aim of measuring different aspects of the baseline neurological function, 4º months, and 8º 12º months, and then yearly. The researchers compared changes in average QNPZ-8 scores, a score of averaged over eight fine motor control testing, processing speed, verbal learning, verbal memory and "executive function," or comprehensive monitoring of cognitive functions.
Participants in this substudy came from South America (42%), Europe (25%), Thailand (15%), the United States (14%) and Australia (4%). Two-thirds were male and the average age was 34 years. About 8% had previous psychiatric diagnosis and 5% reported alcoholism or drug addiction.
They have been described as "a high-functioning group" with 76% being employed and 80% did not receive any training or attended college and / or university or educational training; this is relevant because previous research has shown a link between neurocognitive performance and level of education.
Over two years of follow-up, QNPZ-8 scores increased in parallel baseline, increasing by similar amounts in the arms of early study immediate and delayed start of ART. It notes that Price probably reflects a "practical" view when people repeatedly testing. The estimated difference between the two groups was -0,01, which was not statistically significant. By 60º month, scores in immediate HAART arm increased more sharply, while the participants of the early group delayed group decreased, but there were only a small number of participants and they are still being followed to date and Price said "that this divergence should be closely monitored. "
This study showed "a non-global cognitive advantage (or disadvantage) between the immediate beginning of arms of ART in asymptomatic patients between individuals" naïve "with high count CD4," the researchers concluded. These findings suggest that there is a "low incidence of" preventive ART "for cognitive impairment" in this population and a low incidence of cognitive decline and treatment, as "there is no clear evidence of neurotoxicity. '
In response to a question, said the use of efavirenz (Sustiva) - A component of some antiretroviral therapy regimens known for tropism for the central nervous system and causes psychosomatic side effects - was very common among participants. It was observed that "There is no obvious effects of efavirenz"But it is being analyzed in more detail (Translator's note: This statement is almost like that cover the sun with a sieve because my experience in my service via app whats shows often intense suffering and degeneration of the patients state of mind that make the use of efavirenz and few months ago, a mistake, I received a box of Efavirenz and, thinking there had been a change in treatment, I took ONE of these Efavirenz tablets and the experience was BAD).
Taken together, these studies offer the guarantee that the beginning HAART does not lead to serious or clinically significant adverse outcomes, but most bone loss observed in the immediate start arm It is cause for concern (Here is a complete studyin English and in another site). On the other hand, the sub-studies also did not reveal major advantages to immediate ART with respect to bone, lung or neurological outcome.
A limitation of all these sub-studies is that they get registered with a relatively young population with newly diagnosed HIV and good immune function. Observational studies saw higher rates of cardiovascular disease, neurological and other conditions among people with HIV have observed, in general, groups of older patients, and problems can increase in this group as they age.
Moreover, as noted, the random part of the delayed onset was stopped early, so that the average of three years of follow up was less than expected. Researchers continue to follow participants and observe the long-term results and the sub-studies of cardiovascular and liver disease are also underway. However, now that both arms were advised to initiate treatment, the differences between them are likely to decrease over time.
Translated by Claudio Souza.
Reviewed by Mara Macedo
Kunisaki KM et al.Lung function decline in HIV: effects of immediate versus deferred ART treatment on lung function decline in a multi-site, international, randomized controlled trial.15thEuropean AIDS Conference and 17thInternational Workshop on Co-morbidities and Adverse Drug Reactions in HIV. Barcelona, abstract PS1 / 1, 2015.
And Wright et al. (Price presenting R)The difference between the effects of immediate versus deferred ART on neuropsychological test performance in HIV-positive ddults with CD4 + cell counts above 500 cells / uL: the Strategic Timing of Antiretroviral Treatment (START) substudy neurology.15thEuropean AIDS Conference. Barcelona, abstract PS10 / 6, 2015.