Low Viral Load of HIV Raises Risk of Disease Progression to AIDS and Most Risk of Comorbidities?
HIV-positive people with low viral loads, but detectable in the range of 50 to 500 or even 1000 copies / ml, may continue to have a high risk of AIDS-related events, but their chances of suffering from serious non-AIDS events, including heart, liver and kidney disease do not appear to increase, according to two Italian studies presented at the XV European AIDS Conference in Barcelona.
It is well known that effective combination of antiretroviral therapy (ART / Cocktail), which suppresses HIV replication, dramatically reduces disease progression and improves the life of the person with HIV. Recent Findings of the Great Start Study showed that people who started treatment shortly after diagnosis had a lower risk of developing AIDS-related illnesses and non-AIDS events, as well as the occurrence of deaths, compared with those who waited until their CD4 T cell counts fell to the old "Standard level" of 350 T cells CD4 per milliliter of blood.
A small proportion of people with HIV have shown low but detectable viral load persistently despite the fact that treatment and the effects of low level viremia are not fully understood. Even a low level of ongoing viral replication can lead to increased immune activation and inflammation, which may contribute to non-AIDS-related comorbidities such as heart disease, cancer and clot formation, which can cause stroke and pulmonary embolism. However, large observational studies have not previously observed the association between low viremia and increased risk of AIDS and non-AIDS-related diseases or deaths.
Andrea Antinori and her colleagues, with the ICONA Foundation, conducted a cohort study that demonstrated an estimate of 3 months of incidence of AIDS-related events, serious non-AIDS events, or deaths among people with low viremia , compared to those with viral loads below 50 copies / ml (undetectable).
The analysis included 7277 participants from the Italian cohort ICONA, who had at least 1 person / year follow-up with a viral load in the range of 0 to 1000 copies / ml, at least 6 months after the start of a first-line antiretroviral combination. Three quarters were men, mostly white, mean age of 37 years and 18% were co-infected with hepatitis C virus. The mean CD4 count at the start of ART was approximately 300 cells / mm3 and 13% had been diagnosed with AIDS. The most common regimen of Antiretroviral Therapy was the combination of Sustiva (Efavirenz) with Tenofovir / Emtricitabine (Truvada, also used in PrEP), but a wide variety of other drugs were also used.
The participating investigators were classified into 4 groups, according to viral load count six months after the initiation of ART:
- 0-50 copies / ml (n = 3919);
- 51-200 copies / ml (n = 1811);
- 201-500 copies / ml (n = 1117);
- 500-1000 copies / ml (n = 430).
They compared two results of effectiveness of treatment of viral load groups: AIDS or death from any cause, and non-AIDS events serious according to the definition.
- 204 events related to AIDS or deaths occurred during 28,429 people / year of follow-up.
- Incidence rates of AIDS or death related events were 0,52, 1,25, 1,91, and 1,06 per 100 people / year for participants with viral loads of 0-50, 51-200, 201-500, and 500-1000 copies / ml , respectively.
- The adjusted risk of AIDS-related events or death was 1,74 (74%), 2,30 (more than double the risk, 130%) and 1,30 (30% increase) for people with 51-200, 201-500, and 500-1000 copies / ml, respectively, compared to those with 0-50 copies / ml. These differences were statistically significant for the 51-200 and 201-500 groups, but not for the 500-1000 group.
- 438 serious non-AIDS-related events, or deaths, occurred during follow-up.
- Incidence rates of serious non-AIDS or death events were 1,46, 1,77, 1,69 and 2,56 for their respective viral load groups.
- The adjusted risk of serious non-AIDS or death related events was 1,09 (low change - 9%), 1,00 (difference), and 1,54 (54% increase) for people with 51-200, 201-500, and 500 -1000 copies / ml, respectively, none of which were statistically significant.
"The low viral load, in the range of 51 to 500 copies / ml cubic of blood, was associated with an independent risk of developing a new AIDS diagnosis, which was up to 2,3 times greater than that observed in the presence of suppressed viral load "The researchers concluded.
"On the other hand, the low level of viremia seemed to predict a higher risk of serious non-AIDS-related events". [Translator's note: I kept this phrase in bold literally the same as the original, although I am not a scientist, it seemed to me more like a "guess" than a scientific conclusion. The original is as follows:"Conversely, low-level viremia did seem to predict a more elevated risk of serious non-AIDS events."
It was noted in this study, however, that the classification of viral load into categories was based on current viral load levels and could not be taken into account for prolonged periods of low viral replication. Occasional viral blipes are not uncommon during treatment, but persistent viremia is a major concern. They also said that the short follow-up period, 3 months, may have underestimated the effects of this long-term condition with regard to possible clinical outcomes.
These results, he added, "may be useful in planning analyzes designed to better define therapeutic failure thresholds valid for clinical purposes and possibly to enhance treatment strategies in detail and on a case-by-case basis."
In the second study, Silvia Costarelli of Hospital San Gerardo de Monza and colleagues with the Italian MASTER Cohort analyzed the association between low level of persistent viremia (HIV RNA between 50 and 400 copies / ml) and increased risk of disease-related events cardiovascular diseases.
This analysis included 4393 people who achieved viral load below 50 copies / ml (NT - undetectable - in Brazil the viral load tests are sensitive to an even lower plateau, in 40 copies of RNA per ml of blood) 6 months after the start of ART at least. About 70% were men, the majority were Italians and the average age of the subjects at the beginning of the age was approximately 40 years. They had relatively advanced HIV disease, with a median CD4 count below 300 cells / mm3. The underlying cardiovascular risk was generally low, with only about 1%, having previous cardiovascular events.
A majority of 3576 patients maintained complete viral suppression and, however, 574 experienced therapeutic failure with viral rebound for 400 copies / ml and 243 had a low level of persistent viremia in two consecutive tests.
Observation of Soropositivo.Org Editor: In what follows below is an account of 93 deaths of people with viral suppression in progress. However, there is no report of CD4 T cell count of each of these patients and not even allude to the average counts of T cells CD4. I make this observation because I follow through Whats App application, giving moral support (a friendly conversation, an exchange of information, and considered, at least with respect to this site and the people who visit this site in search of knowledge and hope a lack of humanity in not mentioning this fact, it is not impossible that some of these patients were with a CD4 count which were to provide the occurrence of an opportunistic disease that, in this context, would have been the real cause of loss a human life, can psychologically torment the people who come into contact with this text are exactly this gradually and gradually viral suppression process.
During follow-up there were 45 cardiovascular events, 57 events related to AIDS and 93 deaths among people with ongoing viral suppression: 18, 53 and 37, respectively, among people with viral rebound and 6, 5 and 4 among people with low persistent viremia.
The researchers considered two composite outcomes: first cardiovascular event, event related to AIDS or death and first cardiovascular event or death, ignoring AIDS.
For the first outcome the incidence adjustments were 11,7, 21,6 and 9,3 per 1000 person / years, respectively; for people with complete viral suppression, viral rebound, and persistent low-level viremia. For the second outcome the incidence rates were 8,6, 11,6 and 9,0, respectively. That is, the risk of adverse events was about 2 times greater for people with viral rebound when AIDS was considered, but not when considering only cardiovascular events or deaths.
In a multivariate analysis, patients with viral rebound had a significantly higher risk for the first and second compo- sition points than those with continuous viral suppression (risk ratio 2,15 and 1,5, respectively). However, persistence of low-level viremia was not associated with significantly different risk rates.
"Our results suggest that the low level of persistent viremia does not influence cardiovascular disease," the researchers concluded. "In addition, in our setting, the persistence of low-level viremia was still not significantly capable of influencing the establishment of an AIDS or death.
In summary, the incidence of cardiovascular events, AIDS, and death were similar for those with continuous viral suppression and those with persistent low-level viremia in the MASTER study, suggesting that low-level viral load does not increase the risk of related events or not. This conflicts with the results of ICONA, which showed a higher risk of AIDS among people with low but detectable viral load.
Written by Liz Highleyman
Translated by Claudio Souza Original in English Does Low-level HIV Viral Load Raise the Risk of Disease Progression and Comorbidities?
reviewed by Bob Volpe (Tantus Nominum pair nullum Elogium)
An Antinori, UM Cozzi Lepri, Ammassari, et al. Low level of viremia (LLV) ranging from 50 to 500 copies / ml is associated with an increased risk of AIDS events in the Icona cohort Foundation. XV European AIDS Conference. Barcelona, 21-24 October, 2015. PS4 / 2 Summary.
S Costarelli, D Bernasconi, G. Lapadula, et al. The persistence of low level HIV viremia and cardiovascular risk. XV European AIDS Conference. Barcelona, 21-24 October, 2015. Abstract12 / 10 PE.