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Evan Wood, MD, PhD, FRCPC, discusses the clinical examination for early HIV infection.
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Evan Wood, MD, PhD, FRCPC, discusses the clinical examination for early HIV infection.
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Segment:0 .
>> Hello and welcome to "JAMAevidence," our monthly podcast focused on core issues in evidence-based medicine. I'm David Simel, the Editor of the "Rational Clinical Examination Series" and Professor of Medicine at the Durham Veterans Affairs Medical Center and Duke University. Today we're discussing the clinical evaluation for early HIV disease. Joining me to talk about this topic is Evan Wood, MD, PhD, Professor of Medicine at the University of British Columbia in Vancouver and the Director of the British Columbia Center on Substance Abuse.
Welcome Dr. Wood. To get us started, I'd like to fully understand the role of screening for HIV disease. And to do that, I need to understand the phases of infection. Could you go over those for me? >> Yeah. For sure. So there is three defined phases with HIV/AIDS and that begins with the initial phase of what we sometimes call acute HIV infection or early HIV infection, which is really the first six-month window after HIV acquisition.
Usually, this is a period where recently infected individuals often experience what we call acute retroviral syndrome and the generalized symptoms suggestive of acute viral illness. And this is really what most of us learned about in medical school and classically, in the textbooks at least, involves lymphadenopathy, fever. And when you read about early HIV infection, you, sort of, are taught that you're supposed to have this a-ha moment when you see this lymphadenopathy in a high-risk individual.
In reality, and we can talk about this a bit more because it's the focus of the article, it's a little more complicated than that. But after this approximately six-month first period, is the latent phase of HIV infection. This is when, essentially, individuals are for the most part asymptomatic and from a public health perspective is really the concerning period because if HIV doesn't get diagnosed early, then an individual has a decade where they might be engaging in unsafe behaviors and the opportunity to pass on HIV infection to others.
And then the last phase that I think people are really familiar with is acquired immunodeficiency syndrome or AIDS and that's when the immune system is, sort of, reduced in function to the point where infections that typically are only seen in that context begin to emerge. So things like oral candidiasis or thrush or Pneumocystis jiroveci pneumonia, what we used to call PCP pneumonia, as well as certain things like weight loss or AIDS wasting syndrome tend to present in that last phase of HIV infection.
>> Well, in the "Rational Clinical Exam Series," we try to quantify how well our clinical examination works but to do that we have to understand the incidence and prevalence of the disease that we're concerned with. So for HIV disease, the incidence will quantify the number of new cases over a period of time and the prevalence refers to the number of cases in a population. What do the latest data tell us about the incidence and prevalence of HIV infection?
>> So the global estimates in terms of prevalence suggest that there's about 37 million people that are infected and living with HIV globally with a little more than about a million cases of people living with HIV in the United States. Importantly, I think, when it comes to U.S. data, it's estimated that around 15% to 20% of the HIV-positive U.S. population actually doesn't know that they're infected with HIV.
So about a million people, roughly 15%, probably don't know that they're infected in the USA. In terms of incidents, so new infections annually, there's about 1.8 million new HIV infections that occur annually by the latest estimates with about 40,000 new cases of HIV in the United States each year. And then in terms of the different populations, about 70% of new cases are still among men who have sex with men, about 20% of new cases among individuals who acquired HIV through heterosexual sex, and about 10% are from sharing needles, so people who are using heroin or other drugs intravenously and acquiring HIV in that way.
>> You mentioned that about 15% of patients who are infected by HIV don't know that. So I assume that they must've gone through some sort of acute retroviral syndrome that you also mentioned. Tell me a little bit more about what that syndrome looks like. >> That's really the focus of our article. What we found from the literature is that anywhere from about 50% to 90%, depending on the study, develop this acute retroviral syndrome.
So importantly, there are some people who may not or at least may not know. You know, they may feel a little bit fluey but it's something that they don't remember and they don't report later when they get a diagnosis. So not everyone gets the syndrome but the majority probably do and some estimates up to about 90% of people getting this acute retroviral syndrome that's really characterized by a constellation of quite non-specific symptoms including things like fever, nausea and vomiting. Patients may report arthralgias or myalgias.
Pharyngitis can be classically part of that as well as rash and lymphadenopathy. So really, kind of, classic symptoms that, in the HIV case, we know is from the viremia that goes along with HIV infection but really symptoms that clinicians would recognize or identify with any syndromic viral infection. >> Yeah. Those symptoms are just so common. Are there any symptoms or signs that have reasonably good likelihood ratios so that I can separate out those who have HIV infection from some other viral syndrome?
>> Yeah. You know, when we systematically reviewed this literature, there is several findings with a likelihood ratio that are sort of on the range of four or a little bit greater. Things like genital ulcers which are typically herpes ulcers, weight loss, vomiting, and lymphadenopathy where the findings that we found that were useful in that, sort of, order of a likelihood ratio of better than four and in the range of four. And then we found a host of findings including fever and oral candidiasis that have a likelihood ratio on the order of between three and four.
No real, kind of, slam-dunk type findings. >> Do any of those work better in combination? >> So, there were several studies, none of which that had been replicated or really validated that looked at combination of findings. And in some of these scales, it was four findings. In another study it was up to 17 findings. And what we found when we calculated the likelihood ratios is that certainly with cutoff values of four or more findings, you could get a nice likelihood ratio on an order of 10.
If you had less than four findings, a likelihood ratio on the order of .4. But the challenge with these studies is that, as I mentioned, they haven't been replicated. In some cases, they're in very specific populations such as sex workers in Africa and how applicable that might be to the population that you're seeing in another context. I think what we've learned from these studies is that if you have more findings, it probably improves your likelihood ratio and increases the likelihood of HIV but unlike some of these other really well-validated scoring systems, there is nothing like that in the case of early HIV infection, unfortunately.
>> Okay. In my busy clinic, a primary care clinic, most patients are asymptomatic for anything that resembles an early retroviral syndrome. So it's a lot easier for me to just avoid the issue of screening altogether. Are there any symptoms or signs that when absent provide me reassurance that it's okay to skip screening for HIV disease? >> Yeah. Unfortunately, that's not the case and we actually found that the absence of any signs or symptoms wasn't really helpful.
We didn't find the absence of any sign or symptom that gave a likelihood ratio of less than 0.5. So unfortunately, you really can't be reassured if the patient that's sitting across from you doesn't have any signs or symptoms that you can move on and it's not something you need to think about. >> I was hoping you wouldn't say that but with this discussion, it seems pretty clear that we need to consider screening patients with a variety of symptoms such as genital ulcers and lymphadenopathy and viral syndromes but also non-specific symptoms like weight loss, diarrhea, you mentioned arthralgias, fever, just a whole host of things.
On the other hand, you said that the never-screened patient could be HIV-positive and completely asymptomatic so that neither I nor they know that they're HIV-positive. So what do the Center for Disease Control and the U.S. Preventive Health Services Task Force tell us or recommend to us about screening? >> These guidelines for screening really acknowledge exactly the conundrum that you just described and essentially are fairly identical. The U.S. CDC guideline essentially recommends screening for all patients in healthcare settings.
You have to, of course, notify patients before doing tests, and individuals can opt-out, but essentially universal screening is recommended. And then for individuals who are high risk, so an individual in a non-monogamous relationship that's reporting high-risk sexual encounters for instance, should be screened for HIV at least annually, certainly after any high-risk event or if they're presenting with symptoms. The U.S. Preventative Services Task Force is essentially identical, recommending screening at least once for adults.
And then they notice the nuance that there really is insufficient evidence to determine the optimum screening interval but essentially the take-away message is that all adults should be screened at least once and high-risk individuals should be screened at least annually or as needed is what I take away from that. >> Do those recommendations differ at all from the Canadian or European recommendations? Or is the universe consistent in recommending universal screening? >> There is actually a fair amount of variability. So across Canada and different jurisdictions, at least in my own jurisdiction the province of British Columbia, similar to the U.S. CDC, universal testing guidelines are recommended.
Other Canadian jurisdictions are still playing catch up a little bit. If you look at the European Center for Disease Prevention and Control report on this topic, they've highlighted overall low screening rates and lower than optimal and that there is a fair amount of variability in different European jurisdictions. Certainly, the evidence and the weight of evidence is around screening all adults but there are still some jurisdictions where the rates of testing are not where they really need to be. >> Okay. Is there anything else then you'd like to tell our listeners about the role of the clinical examination in screening for early HIV infection?
>> You know, I think the key messages from the article are that academically there are some findings that appear to modestly increase the likelihood if they're present but overall the prevalence is so low that these findings are not particularly helpful. So for instance in the article we describe a sexually active woman with a few recent high-risk sexual encounters presenting with symptoms consistent with a viral infection. And based on the literature, in North America at least, we could presume a prevalence of HIV infection in that context of about 1%.
So with those [inaudible] of viral symptoms that we've been talking about and you apply the likelihood ratios from the article, the likelihood of HIV infection only goes up to about 5%, so they're not really helpful to discern really high-risk people from low-risk people. And then, as we've talked about, the absence of symptoms and signs isn't really helpful either, which leads to the, sort of, latest science on epidemiology and the public health and clinical management of HIV. And essentially the epidemiology shows that when individuals know they're HIV positive, they do change their behavior.
They're likely to take steps like using condoms to protect their sexual partner, so that's one rationale for screening everyone. Second, we know that clinically when HIV presents late after people have developed late stage HIV disease, they may have a diagnosis of AIDS. Even with the best HIV care that we have in terms of antiretroviral therapy, their survival is reduced in comparison to individuals who are diagnosed and start HIV treatment sooner. And then the last, sort of, big innovation in HIV care, which I'm sure your listeners will have heard about, is that we know that by treating HIV infection and making people's viral load undetectable, their likelihood of passing on the virus to others approaches zero.
So there is a host of, sort of, public health, clinical reasons that we should really be looking to diagnose and treat HIV infection sooner. And really despite what you may have learned in medical school, in the classroom about early HIV infection and that you can, sort of, be watching for it and have this a-ha moment and make the diagnosis of early HIV infection, the reality is that the signs and symptoms are so non-specific and the absence of those signs and symptoms isn't particularly helpful, that from a clinical epidemiology perspective, if you layer that against the low pre-test probability or the low prevalence of HIV infection in the first place that we're probably better off screening all of these patients as much as we can.
>> Well, thank you for talking to me today about the screening for early HIV disease. It certainly helped explain why the health care system that I work in, the Department of Veterans Affairs, creates clinical reminders for us when our patients have not been previously screened for HIV infection. More information about this topic is available in the "Rational Clinical Examination" and on our website at jamaevidence.com where you can listen to our entire roster of podcasts.
I'm David Simel and I'll be back with you soon for another edition of "JAMAevidence"' [ Music ]
Segment:0 .
>> Hello and welcome to "JAMAevidence," our monthly podcast focused on core issues in evidence-based medicine. I'm David Simel, the Editor of the "Rational Clinical Examination Series" and Professor of Medicine at the Durham Veterans Affairs Medical Center and Duke University. Today we're discussing the clinical evaluation for early HIV disease. Joining me to talk about this topic is Evan Wood, MD, PhD, Professor of Medicine at the University of British Columbia in Vancouver and the Director of the British Columbia Center on Substance Abuse.
Welcome Dr. Wood. To get us started, I'd like to fully understand the role of screening for HIV disease. And to do that, I need to understand the phases of infection. Could you go over those for me? >> Yeah. For sure. So there is three defined phases with HIV/AIDS and that begins with the initial phase of what we sometimes call acute HIV infection or early HIV infection, which is really the first six-month window after HIV acquisition.
Usually, this is a period where recently infected individuals often experience what we call acute retroviral syndrome and the generalized symptoms suggestive of acute viral illness. And this is really what most of us learned about in medical school and classically, in the textbooks at least, involves lymphadenopathy, fever. And when you read about early HIV infection, you, sort of, are taught that you're supposed to have this a-ha moment when you see this lymphadenopathy in a high-risk individual.
In reality, and we can talk about this a bit more because it's the focus of the article, it's a little more complicated than that. But after this approximately six-month first period, is the latent phase of HIV infection. This is when, essentially, individuals are for the most part asymptomatic and from a public health perspective is really the concerning period because if HIV doesn't get diagnosed early, then an individual has a decade where they might be engaging in unsafe behaviors and the opportunity to pass on HIV infection to others.
And then the last phase that I think people are really familiar with is acquired immunodeficiency syndrome or AIDS and that's when the immune system is, sort of, reduced in function to the point where infections that typically are only seen in that context begin to emerge. So things like oral candidiasis or thrush or Pneumocystis jiroveci pneumonia, what we used to call PCP pneumonia, as well as certain things like weight loss or AIDS wasting syndrome tend to present in that last phase of HIV infection.
>> Well, in the "Rational Clinical Exam Series," we try to quantify how well our clinical examination works but to do that we have to understand the incidence and prevalence of the disease that we're concerned with. So for HIV disease, the incidence will quantify the number of new cases over a period of time and the prevalence refers to the number of cases in a population. What do the latest data tell us about the incidence and prevalence of HIV infection?
>> So the global estimates in terms of prevalence suggest that there's about 37 million people that are infected and living with HIV globally with a little more than about a million cases of people living with HIV in the United States. Importantly, I think, when it comes to U.S. data, it's estimated that around 15% to 20% of the HIV-positive U.S. population actually doesn't know that they're infected with HIV.
So about a million people, roughly 15%, probably don't know that they're infected in the USA. In terms of incidents, so new infections annually, there's about 1.8 million new HIV infections that occur annually by the latest estimates with about 40,000 new cases of HIV in the United States each year. And then in terms of the different populations, about 70% of new cases are still among men who have sex with men, about 20% of new cases among individuals who acquired HIV through heterosexual sex, and about 10% are from sharing needles, so people who are using heroin or other drugs intravenously and acquiring HIV in that way.
>> You mentioned that about 15% of patients who are infected by HIV don't know that. So I assume that they must've gone through some sort of acute retroviral syndrome that you also mentioned. Tell me a little bit more about what that syndrome looks like. >> That's really the focus of our article. What we found from the literature is that anywhere from about 50% to 90%, depending on the study, develop this acute retroviral syndrome.
So importantly, there are some people who may not or at least may not know. You know, they may feel a little bit fluey but it's something that they don't remember and they don't report later when they get a diagnosis. So not everyone gets the syndrome but the majority probably do and some estimates up to about 90% of people getting this acute retroviral syndrome that's really characterized by a constellation of quite non-specific symptoms including things like fever, nausea and vomiting. Patients may report arthralgias or myalgias.
Pharyngitis can be classically part of that as well as rash and lymphadenopathy. So really, kind of, classic symptoms that, in the HIV case, we know is from the viremia that goes along with HIV infection but really symptoms that clinicians would recognize or identify with any syndromic viral infection. >> Yeah. Those symptoms are just so common. Are there any symptoms or signs that have reasonably good likelihood ratios so that I can separate out those who have HIV infection from some other viral syndrome?
>> Yeah. You know, when we systematically reviewed this literature, there is several findings with a likelihood ratio that are sort of on the range of four or a little bit greater. Things like genital ulcers which are typically herpes ulcers, weight loss, vomiting, and lymphadenopathy where the findings that we found that were useful in that, sort of, order of a likelihood ratio of better than four and in the range of four. And then we found a host of findings including fever and oral candidiasis that have a likelihood ratio on the order of between three and four.
No real, kind of, slam-dunk type findings. >> Do any of those work better in combination? >> So, there were several studies, none of which that had been replicated or really validated that looked at combination of findings. And in some of these scales, it was four findings. In another study it was up to 17 findings. And what we found when we calculated the likelihood ratios is that certainly with cutoff values of four or more findings, you could get a nice likelihood ratio on an order of 10.
If you had less than four findings, a likelihood ratio on the order of .4. But the challenge with these studies is that, as I mentioned, they haven't been replicated. In some cases, they're in very specific populations such as sex workers in Africa and how applicable that might be to the population that you're seeing in another context. I think what we've learned from these studies is that if you have more findings, it probably improves your likelihood ratio and increases the likelihood of HIV but unlike some of these other really well-validated scoring systems, there is nothing like that in the case of early HIV infection, unfortunately.
>> Okay. In my busy clinic, a primary care clinic, most patients are asymptomatic for anything that resembles an early retroviral syndrome. So it's a lot easier for me to just avoid the issue of screening altogether. Are there any symptoms or signs that when absent provide me reassurance that it's okay to skip screening for HIV disease? >> Yeah. Unfortunately, that's not the case and we actually found that the absence of any signs or symptoms wasn't really helpful.
We didn't find the absence of any sign or symptom that gave a likelihood ratio of less than 0.5. So unfortunately, you really can't be reassured if the patient that's sitting across from you doesn't have any signs or symptoms that you can move on and it's not something you need to think about. >> I was hoping you wouldn't say that but with this discussion, it seems pretty clear that we need to consider screening patients with a variety of symptoms such as genital ulcers and lymphadenopathy and viral syndromes but also non-specific symptoms like weight loss, diarrhea, you mentioned arthralgias, fever, just a whole host of things.
On the other hand, you said that the never-screened patient could be HIV-positive and completely asymptomatic so that neither I nor they know that they're HIV-positive. So what do the Center for Disease Control and the U.S. Preventive Health Services Task Force tell us or recommend to us about screening? >> These guidelines for screening really acknowledge exactly the conundrum that you just described and essentially are fairly identical. The U.S. CDC guideline essentially recommends screening for all patients in healthcare settings.
You have to, of course, notify patients before doing tests, and individuals can opt-out, but essentially universal screening is recommended. And then for individuals who are high risk, so an individual in a non-monogamous relationship that's reporting high-risk sexual encounters for instance, should be screened for HIV at least annually, certainly after any high-risk event or if they're presenting with symptoms. The U.S. Preventative Services Task Force is essentially identical, recommending screening at least once for adults.
And then they notice the nuance that there really is insufficient evidence to determine the optimum screening interval but essentially the take-away message is that all adults should be screened at least once and high-risk individuals should be screened at least annually or as needed is what I take away from that. >> Do those recommendations differ at all from the Canadian or European recommendations? Or is the universe consistent in recommending universal screening? >> There is actually a fair amount of variability. So across Canada and different jurisdictions, at least in my own jurisdiction the province of British Columbia, similar to the U.S. CDC, universal testing guidelines are recommended.
Other Canadian jurisdictions are still playing catch up a little bit. If you look at the European Center for Disease Prevention and Control report on this topic, they've highlighted overall low screening rates and lower than optimal and that there is a fair amount of variability in different European jurisdictions. Certainly, the evidence and the weight of evidence is around screening all adults but there are still some jurisdictions where the rates of testing are not where they really need to be. >> Okay. Is there anything else then you'd like to tell our listeners about the role of the clinical examination in screening for early HIV infection?
>> You know, I think the key messages from the article are that academically there are some findings that appear to modestly increase the likelihood if they're present but overall the prevalence is so low that these findings are not particularly helpful. So for instance in the article we describe a sexually active woman with a few recent high-risk sexual encounters presenting with symptoms consistent with a viral infection. And based on the literature, in North America at least, we could presume a prevalence of HIV infection in that context of about 1%.
So with those [inaudible] of viral symptoms that we've been talking about and you apply the likelihood ratios from the article, the likelihood of HIV infection only goes up to about 5%, so they're not really helpful to discern really high-risk people from low-risk people. And then, as we've talked about, the absence of symptoms and signs isn't really helpful either, which leads to the, sort of, latest science on epidemiology and the public health and clinical management of HIV. And essentially the epidemiology shows that when individuals know they're HIV positive, they do change their behavior.
They're likely to take steps like using condoms to protect their sexual partner, so that's one rationale for screening everyone. Second, we know that clinically when HIV presents late after people have developed late stage HIV disease, they may have a diagnosis of AIDS. Even with the best HIV care that we have in terms of antiretroviral therapy, their survival is reduced in comparison to individuals who are diagnosed and start HIV treatment sooner. And then the last, sort of, big innovation in HIV care, which I'm sure your listeners will have heard about, is that we know that by treating HIV infection and making people's viral load undetectable, their likelihood of passing on the virus to others approaches zero.
So there is a host of, sort of, public health, clinical reasons that we should really be looking to diagnose and treat HIV infection sooner. And really despite what you may have learned in medical school, in the classroom about early HIV infection and that you can, sort of, be watching for it and have this a-ha moment and make the diagnosis of early HIV infection, the reality is that the signs and symptoms are so non-specific and the absence of those signs and symptoms isn't particularly helpful, that from a clinical epidemiology perspective, if you layer that against the low pre-test probability or the low prevalence of HIV infection in the first place that we're probably better off screening all of these patients as much as we can.
>> Well, thank you for talking to me today about the screening for early HIV disease. It certainly helped explain why the health care system that I work in, the Department of Veterans Affairs, creates clinical reminders for us when our patients have not been previously screened for HIV infection. More information about this topic is available in the "Rational Clinical Examination" and on our website at jamaevidence.com where you can listen to our entire roster of podcasts.
I'm David Simel and I'll be back with you soon for another edition of "JAMAevidence"' [ Music ]
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