During the practice of HIV care, I have often come across this curious phenomenon of Immunovirological discordance. Here the patient comes with a falling CD4 count over time but the plasma viral load too remains undetectable. These patients also test negative for coexistant HIV -II, HBsAg or HCV infection and also don't have any opportunistic infections. MY follow up of a small group of such patients over 6 months showed that almost half develop increased viral load but the rest continue to have persistent IV discordance. How would you approach such a patient, both for evaluation and therapy.
It is possible that persistent IV discordance could prevail in the subset of patients who started ART in very poor CD4 count (NADIR), thus difficult to achieve an effective immunological recovery even if a virologically suppressing ART. Evaluating the relevance of immune supplements could be of great asset in boosting immune response among patients with such profile.
Dear Dr Joseph Fokam,
In the early stages of therapy when the CD4 is very low, I agree with your logic. Immunological recovery may lag behing virological suppression and this phenomenon can be seen in that context. However, such a phenomenon has also been observed later in the course of the disease, in patients who have taken antiretroviral therapy for a few years.
I wonder why?
regards
This phenomena is fairly common and I have seen it in some of my patients. I used to change ART medications or intensify therapy hoping this would change but I have not been able to identify any strategy that appears to work consistently. It appears though to be related to co-existing Hepatitis C infection and sometimes age. I also have a few patients who have very low viral loads on initiating therapy who never achieve immunologic recovery after starting ART and staying suppressed for several years. Studies have shown such patients tend to have higher incidence of cardiovascular outcomes, (van Lelyved et al AIDS; 2012, 26 (4) 465 -479). This has been associated with significant chronic ongoing immune activation even in the setting of a suppressive ART regimen.
This could possibly be due to viral replication in the gut associated lymph tissue (Chun et al., 2008 JID; Guadalupe et al., 2006 Journal of Virology). Probiotics containing multiple strains but definitely inclusive of lactobacillus AND bifidobacterium strains have boosted an immune response in the context of viral suppression. Probiotics help to shift the gut microbiome and stimulate T cell responses (Th17 and others) and IL-10. Probiotics are safe and over the counter, but not FDA regulated. They also help improve GI symptoms and have demonstrated an association with reduction in microbial translocation (Wilson, Moneyham, & Alexandrov, 2013) which is associated with many of the HIV associated disease progression. Anecdotally, my patients have loved them. I only had one patient that had cramping which also may have been associated with an increase in fiber at the same time. We just discontinued both. Otherwise, patients loved taken probiotics such as Align or Phillips Colon Health but they have many more and higher grade at health food stores. Probiotics are a nutritional recommendation and not a prescription.
Dear Dr Leonard Anang Sowah,
Thanks for the inputs. I too usually change the regimen hoping for a better outcome. The bit of CVS mortality is interesting and I shall look up the paper.
regards
Dear Ms Natalie L Wilson,
I wonder if we are talking about the same thing. I went through the paper of Chun et al. There he speaks about 3 patients who were initiated HAART during primary HIV infection and opted to interrupt treatment later due to personal reasons All of them had high plasma viral load (PVL) and also a high CD4 count. Yes, it is an Immunovirological discordance of one kind, but is the norm in early stages of the disease where the PVL is high and CD4 is yet to decline.
What I am interested in is the discordance that we see in the later part of disease when ART usually gets started. These patients (especially in India and many other asian and african countries) who present late in the diseasewith very low CD4 count and high PVL, do show suppression of PVL but Immunological recovery lags behind. On follow up visits, the PVL is undetectable, but the CD4 continues to be very low. The strategy at this point is not very well defined.
I am also a bit confused about how probiotics can help in this situation? Not too clear if the CD4 counts would improve with them.
regards
Discordance is seen a bit more on patients on Zidovudine based regimens and elderly HIV patients.So if a patient is on Zidovudine based regimen it may be changed.
In routine practice we rarely alter ART if viral load is undetectable.
However these patients need OI prophylaxis depending on their CD4 counts.Preventing OI is important in such patients
Dear Dr Deepak:
It is true that, regardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir is more likely than zidovudine to retain antiviral activity (Tang et al., J Infect Dis. 2013). Because this paper was mainly based on emerging drug resistance mutations. I wonder if the conclusion could have any relation with persistent IV discordance addressed by Dr Shankar?
These cases are not common in our country. However, we've encoutered some cases of that kind with some patients starting treatment in Kinshasa. What I could say is to document the follow up of these cases, compare them with different publications from different countries... and publish. For we all know that in the field of HIV infection, it's always on a case to case basis for our patient.
Dear Kamangu Ntambwe Erick,
Yes, We did follow up a small group of patients over 6 months. We will be publishing the results soon
regards
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