HIV care for the internist with author and HIV expert, Michael Saag MD, Professor of Infectious Diseases at University of Alabama and founder of the 1917 Clinic. We discuss the specifics of screening & diagnostic testing in HIV, monitoring CD4 counts and viral loads, first line antiretroviral therapy, harm reduction, and how to provide excellent HIV care in your primary care clinic.
Written & Produced by: Elena Gibson MS4, Justin Berk MD MBA MPH
Artwork by: Elena Gibson MS4
Hosts: Matthew Watto MD, Paul Williams MD, Justin Berk MD MBA MPH
Editor: Matthew Watto MD
Guest: Michael Saag MD
HIV Show Notes
Dr Saag recommends screening every patient for HIV with a fourth generation HIV Ab/Ag test at the initiation of care. In general, consider screening again every 5-10 years, or every time a new STI is diagnosed. If risk factors are identified, screen every 3-4 months and consider starting PrEP (see episode #41 HIV, PrEP, STI screening).
There are two major categories of testing for HIV: 1) the rapid HIV Antibody test and 2) the fourth generation HIV 1&2 Antibody/Antigen test. The rapid HIV antibody test is slightly less sensitive (98% vs. 99.5-99.7%). Dr Saag notes the rapid HIV test is more useful in public health settings or when follow up is uncertain. The fourth-generation antibody/antigen test is used to test for established infection (HIV 1 and 2 Antibodies) and acute phase infection (p24 Antigen: p for protein, 24 for kD -which is where the protein travels on a Western blot). The fourth-generation antibody/antigen test misses infection acquired within the last 10-12 days. Tests become positive at different times following viral infection. On average, the HIV RNA (viral load) is positive at 10 days, HIV Ag at 15-20 days, and HIV Antibody at 30 days. HIV 1 and HIV 2 represent different strains of the virus. In the United States, HIV 1 is far more prevalent than HIV 2. HIV 2 infections primarily occur in West Africa.
First, let the patient know you are ordering an HIV test. If the screening test is positive, schedule a visit to give the diagnosis in person and complete the initial laboratory evaluation to confirm the diagnosis and prepare for treatment. Confirmatory testing and initial follow-up evaluation should include the following: HIV RNA, CD4 count, viral hepatitis screening, STI screening (RPR, Gonorrhea & Chlamydia urine antigen), HLA-B*57:01 allele. HLA-B*57:01 is a genetic marker identified in 5% of white and 1% of black patients (Orkin 2010 PMID: 20375757). If HLA-B*57:01 is present, then abacavir is contraindicated due to risk of a potentially fatal hypersensitivity reaction. If the patient reports anal intercourse, a rectal swab (NAAT) for Gonorrhea/Chlamydia should also be performed.
Have the patient return for follow up to review the information again. Encourage them to bring someone for support. Counsel them on the importance/effectiveness of treatment and describe HIV as a chronic disease with a normal life span. Emphasize the absence of transmission with viral suppression aka Undetectable = Untransmittable (see niaid.nih.gov July 2017). Encourage patients to find one or two people to tell about their HIV diagnosis.
Determine if you are going to treat the patient or if you will refer the patient to an HIV clinic- a key branch point in treatment. Dr Saag aims to initiate treatment within two weeks of the initial diagnosis. Importantly, he reminds us that rapid initiation of therapy is associated with clear benefits in retention in care and medication adherence. There is also evidence of an association between rapid initiation of therapy (day of diagnosis) and improved virologic suppression at one year (Ford. AIDS. 2018 PMID: 29112073). However, most of the research was completed in areas with 50-100 miles distance from a patient’s home to clinic.
Antiretroviral therapy (ART) regimens containing HIV integrase inhibitors are the preferred first line therapy due to their high potency and low side effect profile, according to a recent update on antiretroviral treatment (Saag JAMA 2018 PMID: 30043070). The four integrase inhibitors used are dolutegravir, bictegravir, raltegravir, elvitegravir. Dolutegravir and bictegravir are fixed dose regimens with one pill once daily. Dr Saag recommends starting bictegravir if you plan on same day initiation of ART because dolutegravir is linked with abacavir and requires HLA-B*57:01 testing. Raltegravir is preferred in women who could become pregnant. Recent recommendations suggest the following initial integrase inhibitor based regimens for HIV (NHIVC – Section 3: ART – Table 2 – https://www.hiv.uw.edu/):
Dr Saag notes that the new antiretroviral regimens for HIV have very few drug-drug interactions. Dolutegravir and bictegravir are glucuronidated and not managed by isoenzymes in liver minimizing drug-drug interactions. Raltegravir has the fewest drug-drug interactions out of integrase inhibitors, but the regimen requires a higher pill burden of three pills per day (NHIVC – Section 3: ART – Table 2 – https://www.hiv.uw.edu/).
When starting therapy, check a viral load and CD4 count together at 6 weeks, 3 months and 6 months. Then, check a viral load and CD4 count every 6 months. Once the CD4 count is above 250, and you have a sense this trajectory will continue (e.g. 3-5 undetectable viral load tests and medication adherence), STOP checking CD4 counts! – Saag JAMA 2018 PMID: 30043070. Dr Saag notes “It is wasteful…a CD4 of 480 vs 790 will not change management”. The CD4 count is only relevant when it is below 200 because it denotes risk for opportunistic infection.
A CD4 count is not a measure of immune system function in HIV infection. High level viremia is the culprit for immune dysfunction. Immune system function is related to the presence or absence of virus. This is why IRIS occurs 4-6 weeks after starting HIV treatment when the virus becomes absent/undetectable. As a result, the immune system wakes up and starts to attack previously acquired pathogens.
Missing a dose or two of ART medicine once HIV is suppressed won’t have an effect on the CD4 count. BUT, if someone stops completely, then the virus will rebound in 2-4 weeks. The CD4 count drops quickly once the virus starts to replicate again. Viral replication causes lymphatic tissue inflammation, and adhesion molecules trap CD4 cells in the lymphoid tissue. This pulls CD4 cells out of the bloodstream and counts drop. Inflammation starts to dissipate and the CD4 count can rebound quickly over days to weeks once a patient resumes ART. -Dr Saag’s expert observations
The CD4 count is a calculation derived from the white blood cell count, the percent lymphocytes and the percent CD4.
The different aspects of this equation can change the CD4 count. The %CD4 can provide a more reliable idea of what is going on in cases where the CD4 count is fluctuating.
Dr Saag notes that the best way to preserve health and prevent HIV transmission is to consistently take ART. When it comes to medication adherence and outcomes, consistent follow up is crucial. Thus, missed visits have been associated with significant increases in mortality (Mugavero et al Clinical Infectious Diseases 2009; Horberg et al AIDS Patient Care and STDs 2013). Remember to thank the patient for their visit. If a patient is not taking the medications, explore why without asking why directly. Dr Saag sometimes reminds patients that two decades ago there was no ART and HIV was a death sentence, not a chronic disease.
Listeners will develop a basic approach to the diagnosis and management of HIV in the primary care setting.
After listening to this episode listeners will…
Dr Saag serves as a financial consultant to Merck, Gilead, and ViiV. Doctors Watto, Williams and Berk and Elena Gibson report no relevant financial disclosures.
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Excellent podcast. I thoroughly enjoyed your last episode on HIV. My only recommendation is to make sure your guest answers your questions fully. One example is when you ask Dr. Saag a 2 part question about vaccination (influenza and pneumococcal) and he only discusses the latter. Otherwise, keep up the good work!
Thanks for the great feedback - duly noted!
Extremely informative episode. Listened to this this past weekend, and today I have a patient with AIDS (CD<50) admitted for diarrhea with stool studies positive for Giardia and Cryptosporidium. Thought back to this episode and was thinking about what prophylaxis I should send him home on. I tried to find the updated guidelines, and per aidsinfo.nih.gov, the updated guidelines (march 2018) still recommends what is originally taught in terms of when to start certain prophylactic treatments. Perhaps I misunderstood, but this episode gave me the impression that typically TMP/SMZ is all that is needed even for CD4 counts <50. I was wondering if you could provide the link for the guidelines that were mentioned in the show, and perhaps a clarification?
Hi K, Thanks for the message and sorry for the delayed response! Great question as this seems to against what is often taught in medical school. Based on previous literature (PMID 24833016), there is some evidence that MAC PPx does not statistically help prevent MAC if a patient in on PPx. You are correct that the AIDSInfo guidelines recommend MAC PPx (https://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-opportunistic-infection/326/mac). However, these were last reviewed in June 2017 and are still being updated. The most recent guidelines were published in JAMA in July 2018 with Dr. Saag as lead author (PMID 30043070) and offer a class AIIa recommendation for no prophylaxis for MAC with CD4 < 50, contrary to older teaching! TMP/SMZ for PCP (and potentially Toxoplasmosis) is all that is needed. Hot off the presses! Hope this helps!
Thanks so much for getting back to me! Wow, that's extraordinary! I'm sure my future patients will be glad to hear that as well. :) Thanks again!
Can you please point to a guideline for non HIV + men, who have receptive anal sex and the need for screening Rectal PAP? CDC says insufficient evidence, I would just like to how to practice as I have never heard this guideline before.