HIV drug increases risk of suicidal ideation.
A recent study shows an association between Efavirenz (a common anti-HIV drug) and increased risk for suicidal ideation or attempted or completed suicide. The study conducted by Mollan KR et al., and published in Ann Intern Med. 2014 confirmed the neuropsychiatric effects of Efavirenz. With increased life expectancy of people living with HIV infection – and the opportunity to study the long term effects of drugs – the emergence of drug-induced co-morbidities is concerning.
This underscores the need for the development of longer-acting drugs or treatment modalities that limit the constant (daily) use of antiretroviral therapy. Emerging data also beg the question as to the longer-term benefits of immediate treatment of a young individual with normal CD4 T cell count and low viral load.
Indeed, early treatment reduces inflammation and impacts the size of the viral reservoir – yet the clinical benefits are questionable.
One argument for early treatment is epidemiological-based: “to protect the community”. But we probably can dismiss this one because with fashionable PrEP picking up steam we might all be chewing PrEP candies in the near future.
I think more needs to be done to delay the use of antiretroviral drugs wherever possible, and more reliable measures of inflammation are needed so that we are not only guiding treatment based on CD4 cell counts and viral load but also take into account the levels of inflammation a person has. After all, inflammation (which generally is associated with CD4 T cell count) has been shown to be the best predictor of HIV disease progression and mortality.
Dr Clovis Palmer is a graduate of the University of Sydney, Australia, and holds a PhD in plant biochemistry and molecular genetics. He conducted postdoctoral studies in immunology, liver disease and obesity at the University of New South Wales, Australia.
Dr Palmer is a reviewer for several top-ranked international journals including Hepatology, AIDS and Antioxidants and Redox Signalling. He is the chief scientific editor for Natural Immunity-Health, Australia (www.naturalimmunity.com.au).
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Opinions expressed in this article may not reflect those of THEGAYUK, its management or editorial teams. If you'd like to comment or write a comment, opinion or blog piece, please click here.
Oct 1 2014 01:24AM by Clovis Palmer
By delaying the use of antiretroviral drugs I was particularly referring to the possibility of periodic administration of drugs (once a month for example) to suppress immune activation and inflammation that could slow the progression of HIV.
Specifically, my research team is am studying how we could modify metabolism in immune cells as a strategy to delay HIV disease progression and or to improve CD4 T cell recovery and immune functions in people on ART. I gave an oral presentation on our work at the International AIDS Society Conference, and the Towards an HIV Symposium in Washington DC in 2012. Please view video for a synopsis:
Oct 1 2014 12:28AM by Clovis Palmer
Thanks for reading my article and commendations for your work in the field. Sometimes a few hundred words are not sufficient to cover complex issues. I will address each of your concerns separately
1. I agree Efavirenz is NOT HIV medication it is just one of the dozens of drugs use in the treatment of HIV infection. I can see why you made this point – but I suggest you ask the editors for the title that I actually submitted. Mollan’s recent paper is the best account yet of the effects of Efavirenz.
2. It is not just a matter of just switching drugs as you l know. Viral resistance plays a significant role in drug choice.
3. I am sure you know that I know that Efavirenz is not PrEP. The reference to PrEP was exactly what you said ” People should not be pressured in the name of “protecting the community” to start these drugs if they are for example young, have normal CD4 count, low viral load and asymptomatic. I believe in personal choices and responsibility – that will help to decriminalize HIV in many places.
4. Have you read and analyse the iPrEx study that demonstrated a protection of 44%. Have you analysed the demographics up of the study cohort? If you have not and do, then you might have a different perspective about PrEP. Recent studies also show that Tenofovir use in HIV negative persons was associated with a statistically significant decrease in creatinine clearance (an indicator of renal function), and loss in bone mineral density over an 18 month period. There are definitely some situations where I would advocate PrEP but I think it was rolled out too quickly- and that did more damage than if we waited for more results from other.
5. HIV is the most dynamic disease. We gain significant insights from the SMART study but I tend to concentrate on more recent data. I and others have written and published several reviews and research papers on the most up-to-date findings on HIV- associated inflammation and co-morbidities which can be found in top ranked HIV journals in PubMed, so I invite you to read those for the latest research in this area. Studies by some of the top researchers in the field such as Professor Steven Deeks and Professor Alan Landay have shown that IL-6 is the best marker/predictor of inflammation in PLWH. hs-CRP is the correct maker used in the context of HIV, not CRP, they are different! so if some doctors are measuring only CRP then that should be changed. Other more accurate markers of inflammation are the levels of tissue factor on intermediate monocyte subsets (best predictor of cardiovascular risk in PLWH). CRP is a poor marker of inflammation and disease progression in the context of HIV disease. In our lab we are now exploring even more sensitive markers.
Regarding when to treat and benefits of early treatment this is a debate in the scientific community. Are some of the drugs causing the co-morbidities such as diabetes. I recently went to a presentation and data to be published soon were shared and the answer is yes. Again I specialize in HIV and inflammation so for a more in-depth analysis I am happy to send you my articles or you can find them in the Medical database -PubMed. These have been reviewed by independent pundits in the field.
There is actually not a huge amount of research in the field of therapeutic vaccines and long-lasting products. That is why each scientific meetings I attend I advocate for these. I have attended all the major basic international and national conferences on HIV for the last 8 years and very rarely I see any interest in long-lasting drugs. I know of only a handful of long-lasting drugs, so if you have additional information that I am unaware of I would appreciate if you could please send me the details. Therapeutic vaccine is now an interest as a cure strategy. Were you at AIDS2014? There were some fantastic presentations in this area.
Thanks for your critical comments, we live by these in my field and as a reviewer for several journals I have to give critical comments and evaluation. However, I always offer the authors to rebut or refute. I never requested that they no longer be submit their articles because in our field criticisms are the fuel for perfection.
Sep 28 2014 02:26PM by Gus Cairns
1. Efavirenz (Sustiva, also in Atripla) is NOT “HIV medication”. It is one particular drug, and the fact that it produces neuro-psychiatric side effects in some people has been known ever since it was developed.
2. If people experience side effects, there are alternatives to efavirenz such as nevirapine or rilpivirine.
3. Efavirenz is NOT used as PrEP. The drugs used are tenofovir and emtricitabine, which come from a completely different chemical class and do not have psychiatric side effects.
4. The reference to “chewing PrEP candies” is a gratuitous attempt to trash a very promising additional HIV prevention method for HIV-negative people.
5. The early use of antiretroviral therapy for HIV-positive people IS suggested as a way of reducing the overall infectiousness of people with HIV. It is also extremely effective – essentially, undetectable = infectious – and is also something highly desired by a lot of HIV+ people, who would like to be relieved of the anxiety and guilt of infecting others. But this never should be imposed on patients as a duty in the name of public health.
6. With regard to inflammation: Dr Palmer is arguing against himself here. Studies show that inflammation is raised in people with HIV who are off treatment generally. The “more reliable measures of inflammation” he asked for are already used in the shape of measuring CRP and other inflammation markers. The SMART trial in 2006 was the first of many to establish links between HIV, inflammation indicators and faster disease progression. HIV’s whole modus operandi is to keep the body in a raised state of inflammation so it will have more activated CD4 cells to infect. HIV treatment, by reducing the amount of HIV in the body, reduces inflammation. This is why early treatment is a good idea.
7. About the one thing I agree with in this piece is that we need “longer-acting drugs or treatment modalities that limit the constant (daily) use of antiretroviral therapy”. A huge amount of research is going into the possibility of therapeutic vaccines and long-lasting products that could do exactly that.
In summary:
Altogether, it is amazing how many scientific inaccuracies and misunderstandings have been packed into a relatively short piece. This is pseudoscience masquerading as science, and I recommend you do not use this writer again.