This may be an argument in favor of the use of dolutegravir-based regimens in cases where it is difficult to maintain high levels of adherence or there is an increased risk of treatment interruptions.
A French study, the results of which have been published in the Open Forum Infectious Diseases journal, revealed that people taking antiretroviral regimens based on the integrase inhibitor dolutegravir (Tivicay®; also in Juluca®, Dovato® and Triumeq®) had more likely to achieve sustained viral suppression, even in situations of lower adherence and treatment interruptions, compared to older antiretroviral drug-based regimens (ie, non-nucleoside reverse transcriptase inhibitors [NNRTIs], inhibitors of boosted protease [PI] and even first-generation integrase inhibitors such as raltegravir).
Treatment options for HIV have progressed and improved over time, and today a large proportion of infected people limit their treatment to a single daily tablet.
Despite this, adherence to antiretroviral treatment continues to pose a challenge for many people with HIV. A poor or suboptimal level of adherence can lead to loss of virological control, with the consequent reappearance of a detectable level of viral load. Not only would this put your own health at risk, but it also means that you could transmit HIV to third parties during sexual intercourse. Sub-optimal adherence also creates the ideal conditions for the emergence of drug-resistant viral strains.
When highly active antiretroviral therapy (HAART) first appeared in the 1990s, almost perfect adherence was required to maintain viral suppression and prevent the emergence of resistance. Later, studies that analyzed NNRTIs, boosted PIs, and integrase inhibitors as part of antiretroviral combinations revealed that the minimum level of adherence to maintain viral suppression would be around 80%. However, these studies were based on people's own statements or on pharmacy replacement data, so they were imprecise and did not reflect relevant factors. Furthermore, those analyzes did not include second-generation integrase inhibitors, such as dolutegravir or bictegravir.
There are drug regimens that are resistant to lower adherence and treatment interruptions than others. Thus, it has been found that regimens based on dolutegravir - when it is used as the third drug in HAART - are more flexible in terms of adherence (in maintaining viral load suppression) compared to older antiretrovirals . The World Health Organization (WHO) recommends dolutegravir-based regimens as first- and second-line treatment options for people starting antiretroviral therapy, or when other regimens have failed.
With the aim of offering more evidence on this question, a team of researchers from the University of Caen (France) carried out a prospective, multicenter international study of cohorts - called DOLUCAPS - of people with HIV being treated with an antiretroviral regimen based on dolutegravir. . Enrollment took place between 2015 and 2018, and the study involved adults with HIV from France and Switzerland. Three groups of people taking antiretroviral-based regimens were formed: one made up of people who started taking dolutegravir for the first time, another made up of people who had switched to dolutegravir due to prior virological failure, and a third group made up of people who switched. to this drug while they had undetectable viral load.
Participants were tested for resistance and included those with susceptibility to at least three or more drugs (including dolutegravir). People with poor adherence to antiretroviral treatment were eligible to participate in the study, and those who used pillboxes or those who were not responsible for taking their own medication were excluded.
The study included a total of 399 people, with a mean age of 46 years, with 70% of the participants being men. About 102 participants were taking an antiretroviral regimen based on dolutegravir. At the start of the study, about a quarter of them had not received antiretroviral treatment before. About half of all participants in the group entered the study with a viral load less than 50 copies / mL (46%), and the median CD4 count at baseline was 494 cells / mm3.
Of the remaining participants, 100 were taking NRTIs (70 had nevirapine as the third drug in the combination, 12 efavirenz, and 18 rilpivirine), 107 were receiving boosted PIs (54 lopinavir, 48 atazanavir, and 5 other PIs), and 90 were taking raltegravir.
The investigators compared the dolutegravir group with previously collected adherence data from people with HIV and taking older antiretroviral treatments (NNRTI, boosted PIs, and first-generation PI raltegravir). All centers included in the study used electronic drug monitoring devices, which record each time a bottle of medication is opened, to observe the adherence patterns of each participant over a period of six months.
Both the mean adherence and the duration of treatment interruptions were determined to observe their impact on suppressing viral load (defined as a viral load below 50 copies / mL) at the end of the six months of the study. Resistance to dolutegravir or raltegravir was also monitored.
At the end of the six months of the study, only eight of the 102 people taking dolutegravir had viral loads greater than 50 copies / mL (and in no case greater than 200 copies / mL). Of those eight participants, five had switched to dolutegravir due to previous treatment failure, two had started dolutegravir for the first time, and one participant switched to dolutegravir despite being virally suppressed.
For their part, eighteen people in the raltegravir group had viral loads greater than 50 copies / mL, with a median viral load of 362 copies / mL. Resistance to raltegravir was found in four samples from this group. Twelve people in the NNRTI group had no suppression of HIV viral load, with a median of 854 copies / mL. Neither had 26 participants in the boosted PI group achieved an undetectable viral load, with a median viral replication of 11,000 copies / mL. No resistance data are available for the last two groups.
Mathematical analysis showed that adherence patterns did not significantly affect viral load for people taking dolutegravir, even when mean adherence was in the 60-80% range. This remained the case when treatment interruptions and the interaction between adherence and treatment interruptions were examined.
For all other older drug types, adherence patterns were significantly associated with viral replication at the end of six months. For example, when examining the combined effects of mean adherence and treatment interruptions in people taking raltegravir, 54% of cases of unsuppressed viral load could be explained by the interaction of these two measures, while 40% it could be explained in people taking boosted IPs. For people taking NNRTIs, longer treatment interruptions had a greater effect, accounting for 35% of the observed differences in viral replication.
When people were observed with high mean adherence levels (greater than 95%), there were no significant differences in viral load suppression between dolutegravir-based regimens compared to others, regardless of age, gender, the baseline CD4 count and baseline viral load of the participants. However, this changed significantly when people with lower adherence (less than 95%) were taken into account, as people taking raltegravir were 46 times more likely to have not reached viral suppression than those taking boosted PIs, 28 times more likely and those who took ITINN, 25 times more likely.
In conclusion, the researchers state that, although the goal of antiretroviral treatment should remain consistent and high adherence, the findings of their study make a strong case for the use of dolutegravir-based regimens in people who are using it. high levels of adherence are difficult to maintain or are at increased risk of treatment interruptions for any reason. Furthermore, the study findings suggest that people treated with dolutegravir-based HAART would have a lower risk of detectable viral replication than those treated with older regimens with low to medium adherence levels.
Fuente: Aidsmap / Elaboración propia (gTt).
Referencia: Parienti J-J et al. Forgiveness of Dolutegravir-Based Triple Therapy Compared With Older Antiretroviral Regimens: A Prospective Multicenter Cohort of Adherence Patterns and HIV-RNA Replication. Open Forum Infectious Diseases, 8 (7), 2021. https://doi.org/10.1093/ofid/ofab316