#121 HIV Care for the Internist

October 22, 2018 | By Justin Berk

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.

Credits

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 Pearls from Dr. Saag

1. Dr Saag recommends that clinicians screen every patient for HIV at initiation of care with an HIV 1/2 Antibody/Antigen (Ab/Ag) test and then every 3-4 months if risk factors are identified.
2. Screen for HIV anytime you treat someone for a new sexually transmitted infection (STI). -Dr Saag
3. The HIV Ab/Ag test will only miss individuals infected within the last 10-12 days. HIV viral load (RNA) is positive about 10 days after infection.
4. Follow up a positive HIV Ab/Ag test with an HIV viral load.
5. Screen for HLA-B*57:01 allele in each patient at diagnosis, and do not start treatment with abacavir if this is pending or positive due to abacavir hypersensitivity.
6. Start treatment for HIV within 2 weeks of diagnosis. -Dr Saag
7. Integrase inhibitor regimens are preferred due to potency and low side effect profile.
8. Regimens that include the integrase inhibitors, dolutegravir or bictegravir, are first-line because they provide a one pill per day regimen. Raltegravir probably has the least likelihood of drug-drug interactions, but has a higher pill burden.
9. The CD4 count is not a measure of immune system function!!! A high viral load CAUSES immune system dysfunction! Immune function returns rapidly once the viral load is suppressed. –Dr Saag
10. Dr Saag recommends not following the CD4 count once viral load has been persistently suppressed (Saag JAMA 2018 PMID: 30043070) because it becomes irrelevant to management.

HIV Show Notes

HIV Screening

Who and when to screen

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).

HIV Test Details

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.

HIV – Diagnosis and Management

Initial counseling and evaluation after diagnosis

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.

HIV follow-up visit

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.

Antiretroviral Treatment

Treatment

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.

HIV Antiretroviral Regimens

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/):

1. Bictegravir-tenofovir-emtricitabine
2. Dolutegravir-abacavir-lamivudine
3. Dolutegravir plus tenofovir-emtricitabine

Drug-Drug Interactions

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/).

Monitoring HIV Care

Initial CD4 and Viral Load Testing

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.

CD4 Count vs Viral Load  

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.

Missed ART Doses and CD4

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

CD4 calculation

The CD4 count is a calculation derived from the white blood cell count, the percent lymphocytes and the percent CD4.

CD4 Count = (WBC) * (%Lymphocytes) * (%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.

HIV Counseling – Harm Reduction and Medication Adherence

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.

Goals and Learning Objectives

Goals

Listeners will develop a basic approach to the diagnosis and management of HIV in the primary care setting.

Learning objectives

After listening to this episode listeners will…

1. Identify patients who may benefit from HIV screening
2. Become familiar with limitations and interpretation of various diagnostics tests for HIV
3. Counsel the patient with a new diagnosis of HIV
4. Know the next steps for a patient following an initial HIV diagnosis (labs, tests, treatment, follow up)
5. Track and interpret CD4 counts and viral load testing in patients on therapy for HIV and recall how quickly these tests can change when cycling on and off therapy
6. Recall the first line medical therapy for newly diagnosed HIV and why regimens containing the four integrase inhibitors are prioritized
7. Explain the role of the primary care physician in screening and prevention of cardiovascular disease and cancer in patients with HIV

Disclosures

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.

Time Stamps

• 00:00 Disclaimer, intro, and guest bio
• 04:35 Getting to know our guest, a movie recommendation, and words of wisdom
• 08:48 Clinical case, HIV screening, in-depth discussion of HIV testing & diagnosis
• 15:56 New diagnosis of HIV, counseling after diagnosis, confirmation, follow-up testing, the second visit
• 24:20 Treatment – what to start and when; some basic comments on therapy
• 30:05 Primary care after diagnosis, vaccines, cancer screening, cardiovascular disease prevention
• 34:35 Monitoring CD4 counts and viral load; interpreting CD4 count; time course of response for CD4 and viral load
• 42:02 Harm reduction counseling; addressing medication non-adherence
• 47:40 PCP prophylaxis
• 49:43 The 1917 Clinic, Ryan White Clinics, and linking patients to care
• 53:10 Take home points
• 55:40 Plugs
• 57:45 Will a cure or vaccine for HIV emerge?
• 59:16 Outro

Links from the show

1. Dr Saag’s medical school graduation video – “A Day in the Life” https://vimeo.com/207717873
2. Positive: One Doctors Personal Encounters with Death, Life and the US Healthcare System (book) by Michael Saag MD
3. Mash (film) by Robert Altman
4. National HIV Curriculum – Free and up-to-date learning tool for HIV
5. Check out ClinicWiki.org The Resident-as-Teacher Notebook for Ambulatory Care – contact @justinberk on Twitter to contribute

References

Links have been included in body of text above

1. Saag MS, Benson CA, Gandhi RT, et al. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2018 Recommendations of the International Antiviral Society-USA Panel. JAMA. 2018;320(4):379-396.
2. Orkin C, Wang J, Bergin C, et al. An epidemiologic study to determine the prevalence of the HLA-B*5701 allele among HIV-positive patients in Europe. Pharmacogenetics and genomics. 2010;20(5):307-314.
3. Mugavero MJ, Lin H-Y, Willig JH, et al. Missed Visits and Mortality in Patients Establishing Initial Outpatient HIV Treatment. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2009;48(2):248-256. doi:10.1086/595705.
4. Horberg MA, Hurley LB, Silverberg MJ, Klein DB, Quesenberry CP, Mugavero MJ. Missed Office Visits and Risk of Mortality Among HIV-Infected Subjects in a Large Healthcare System in the United States. AIDS Patient Care and STDs. 2013;27(8):442-449. doi:10.1089/apc.2013.0073.