HIV Overview with Dr. Zachary Yetmar

Podcast Transcript

Introduction

Joya: Welcome to the Internal Medicine Grand Rounders Podcast! I'm Joya, a 3^rd year Internal Medicine Resident at Cleveland Clinic and future ID fellow at Mayo Clinic. Today, we have the privilege of speaking with Dr. Zachary Yetmar, an Infectious Diseases specialist at the Cleveland Clinic, and we're excited to delve into HIV care for the Internist.

1. General info about HIV

Joya: So let’s start with the basics. Dr. Yetmar, could you please give us an idea of the current statistics in the US?

Dr. Yetmar: 

• Worldwide, there are over one million new HIV infections each year. In the United States alone, we see more than 30,000 new cases annually. By the end of 2019, approximately 1.2 million people in the U.S. were living with HIV, with a national prevalence of about 0.3 percent. However, about 1 in 8 people living with HIV don’t yet know they have it, making screening vital. In 2018, there were 15,800 deaths among individuals diagnosed with HIV, equating to a rate of 4.9 per 100,000 people. 
• HIV is primarily acquired through sexual intercourse, exposure to infected blood, and perinatal transmission from mother to child. Consistent condoms use significantly reduces the risk of sexual transmission. Additionally, male circumcision has been shown to decrease the risk for heterosexual men. 
• The U.S. has a plan to reduce new HIV infections by 90% by 2030, focusing on early diagnosis, effective treatment, prevention for at-risk individuals, and rapid response to emerging clusters of infection.

2. Screening for HIV

Joya: Yeah, those are eye-opening statistics, especially when you think about how many people might not even know they’re living with HIV. And that brings me to another important point. In our primary care clinic, we usually screen asymptomatic individuals at least once in their lifetime. But could you share with us who else should be screened and how often should we repeat these tests?

Dr. Yetmar: Screening is crucial. HIV testing should be performed for anyone with signs or symptoms of acute or chronic infection, as well as those with possible exposure. Some patients may have concurrent conditions that are impacted by the presence of HIV (e.g. TB, HBV, HCV). Patients with severe or unusual infections without clear risk factors should be screened. Everyone should be screened at least once in their lifetime, with more frequent testing for those at higher risk, such as individuals with multiple sexual partners, men who have sex with men, people who inject drugs, and pregnant women.

Joya: That’s really helpful to know. So, speaking of HIV screening, what tests are usually used?

Dr. Yetmar: 

• The combination antigen/antibody assay is used for screening. 
• In most settings, if it is negative, the person is considered not to have HIV, and no further testing is required, since the sensitivity and specificity of this combination antigen/antibody assay is reported to be greater than 99%. 
• If the combination antigen p24/HIV antibody assay is positive, a confirmatory HIV-1/HIV-2 antibody differentiation immunoassay is performed. In addition to confirming the diagnosis, the HIV-1/HIV-2 differentiation assay determines if a patient has HIV-1 infection or HIV-2 infection (or both). This distinction has important implications for HIV disease progression and treatment. 
• We check plasma HIV RNA in all patients with an indeterminate test result. There is also a brief period early after infection where our standard HIV screening tests would be negative. If a patient is suspected to have very recently acquired HIV, a plasma HIV RNA should also be sent. 
• Finally, there are rapid HIV tests that use blood from a pinprick or saliva. If these are positive, they should be confirmed with a standard HIV test.

3. HIV prevention 

Joya: Thank you for going over HIV testing. Now let’s talk prevention. We usually rely on a mix of behavioral and medical strategies to prevent infection. For patients who test negative for HIV but remain at risk, could you explain how pre-exposure prophylaxis—or PrEP—fits into the overall prevention approach and who can benefit from it?

Dr. Yetmar: PrEP is a highly effective HIV prevention strategy, particularly for those at high risk of infection and all sexually active patients should be informed about HIV PrEP. It involves taking antiretroviral medications before potential exposure to HIV. The USPSTF has given HIV PrEP a Grade A recommendation, meaning this is an important aspect of primary care for at-risk patients. For PrEP to be effective, adherence to the regimen is crucial, reducing the risk of transmission by over 99%. Candidates for PrEP include men who have sex with men, heterosexually active individuals with high-risk partners, and people who inject drugs. There are two options of administration for PrEP: oral and injectable; both are effective in reducing HIV transmission. The oral drugs for PrEP are co-formulations of tenofovir and emtricitabine (Truvada and Descovy). The current injectable PrEP medication is cabotegravir, given as an intramuscular injection every 8 weeks. Two RCTs, HPTN 083 (in 2020) and HPTN 084 (in 2021), showed that long-acting injectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate–emtricitabine in preventing HIV infection among MSM, transgender women, and women. There are recent studies using a twice-yearly injection called lenacapavir, though this isn’t in routine use yet. The decision to use one strategy over the other depends upon availability and patient preference. Before starting PrEP, it's important to confirm the individual is HIV-negative and assess their overall health, including kidney function and potential for bone disease. Potential challenges to PrEP adherence need to be assessed as well. 

Joya: Keeping an eye on things is important for anyone on PrEP. Is there any blood work or side effects that we need to monitor while someone is on PrEP?

Dr. Yetmar: Patients on PrEP should be monitored regularly. For those on oral PrEP (one of tenofovir formulations), we typically see them one month and three months after starting, then every three months. This includes testing for HIV, screening for sexually transmitted infections, and checking kidney function. Those on injectable PrEP with cabotegravir are followed monthly for the first two months and then every two months. Regular monitoring helps ensure the effectiveness of the regimen and manage any side effects. When a person decides to discontinue PrEP, HIV testing should be performed at the time they discontinue PrEP.
 
Joya: Thank you Dr. Yetmar, that’s a great overview of how we keep patients safe on PrEP. Now, shifting focus a bit—let’s talk about what happens after a potential exposure to HIV. Could you explain postexposure prophylaxis—or PEP—and how soon someone needs to start it if they think they’ve been exposed to HIV?

Dr. Yetmar: Postexposure prophylaxis should be started within 72 hours following HIV exposure with a three-drug regimen of tenofovir plus emtricitabine or lamivudine plus bictegravir or dolutegravir for 4 weeks. Testing for HIV should be done immediately and at 4 to 6 weeks, 12 weeks, and 6 months.

4. Evaluation of recent HIV diagnosis 

Joya: That’s really helpful to know about PEP and the importance of acting quickly after potential exposure. Now, shifting gears a bit—let’s say in our primary care clinic, someone is diagnosed with HIV using the routine antigen/antibody test. What should we focus on during their initial evaluation while they’re waiting to see an infectious disease specialist?

Dr. Yetmar: The initial evaluation is vital. 

• We first need to make sure the patient has a good social support, assess his mental health, and encourage them to bring a loved one with them in the next visits. The diagnosis of HIV can be perceived as isolating and stigmatizing. We need to explain clearly that once the treatment is started, the person can no longer transfer the virus. 
• We assess the stage of HIV disease, identify any comorbidities, and select an appropriate antiretroviral regimen. It's also a time to educate the patient about the disease and establish a strong patient-practitioner relationship. 
• Laboratory tests include CD4 cell count, HIV RNA levels, and genotypic testing to determine any transmitted HIV resistance, along with baseline testing of organ function and testing for potential coinfections, such as viral hepatitis, other STIs (Syphilis, Chlamydia/Gonorrhea). HLA-B5701 is a genetic variant linked to an increased risk of hypersensitivity reactions to the HIV treatment drug abacavir. Screening for this variant is crucial if abacavir is being considered. 
• The START trial in 2015 on The Strategic Timing of Antiretroviral Treatment (START) trial revealed that initiating ART in HIV-positive individuals with higher CD4 counts (>500 cells/mm³) significantly reduced the risk of AIDS-related events and serious non-AIDS events compared to delaying treatment until CD4 counts dropped below 350 cells/mm³. This reinforced the benefit of early ART initiation, ideally within seven days of diagnosis, regardless of CD4 count and with few exceptions, such as a concurrent opportunistic CNS infection.
• Regular monitoring is essential at the start of ART to assess effectiveness. Once we ensure adherence to ART and see persistent undetectable viral loads with CD4 counts above 250, we can reduce the frequency of these tests. Continuing to test beyond this point can be wasteful, as it doesn't change the management of the patient's care. Patients with CD4 counts below 200 often need Pneumocystis prophylaxis and below 100 with a positive Toxoplasma IgG need Toxoplasma prophylaxis with bactrim. We typically do not provide MAC prophylaxis with azithromycin anymore.

5. Complications and preventive care in patients with HIV

Joya: That’s a thorough initial evaluation for a recent diagnosis of HIV. You know, it’s incredible to see how much progress has been made in HIV management. Today, people living with HIV often have a life expectancy that’s almost the same as those without it. But with over a million people living with HIV in the U.S., it makes you wonder—what should primary care doctors really focus on when taking care of these patients in terms of cancer screening or cardiovascular risk evaluation?

Dr. Yetmar: Indeed, antiretroviral therapy has transformed HIV management. Opportunistic diseases have become less common, and mortality has declined such that most treated patients with HIV now have a near-normal life expectancy. Most deaths in patients with HIV receiving ART are now related to conditions other than AIDS. HIV infection appears to increase the risk of non-AIDS-related conditions, including cardiovascular disease, renal disease, bone disease, liver disease, and malignancies. These and other common age-related diseases may occur more frequently and at a younger age than in uninfected persons. This is important to recognize, as common risk calculators such as the ASCVD calculator do not incorporate HIV status. Studies have also shown that prevalence of smoking is higher in the HIV population. 

• We recommend aggressive management of modifiable cardiovascular risk factors such as diabetes mellitus, hypertension, hyperlipidemia, smoking, and obesity. 
• We also recommend bone mineral density screening with dual X-ray absorptiometry (DXA) for all postmenopausal females and males with HIV >50 years of age and cervical cancer screening with pap smears for women with HIV beyond the age of 65. 
• National guidelines recommending anal screening for precancerous lesions have not been adopted by the United States Public Health Service. However, the CDC recommended that all people living with HIV ≥35 years old have substantially elevated anal SCC risk and should be considered for anal cancer prevention interventions, including screening. 
• We also monitor for medication toxicity, checking blood counts, kidney function, and liver enzymes. 
• Patients with HIV are typically also at risk for other STIs and we provide regular screening for these patients, typically every 3-6 months. For gonorrhea and chlamydia screening in particular, it is important to provide site-specific screening. For example, a urine gonorrhea/chlamydia test will evaluate for urethritis but will often be negative if a patient has rectal or pharyngeal infection.

Joya: It’s clear that holistic care goes far beyond just managing the virus itself. Dr. Yetmar, could you walk us through which immunizations are recommended for patients with HIV?

Dr. Yetmar: Vaccination is most effective in patients with early HIV infection and in those on ART who are virologically suppressed and have restored CD4 function. Inactivated vaccines are generally safe and acceptable in individuals with HIV and the recommendations are similar to the regular population (COVID, Influenza, TdaP, HPV). Certain vaccines are indicated upon diagnosis of HIV; these include pneumococcal, HAV, HBV, meningococcal, and zoster. The meningococcal vaccine needs to be repeated every 5 years. Certain live vaccines have sufficient safety data and are thus appropriate if indicated for individuals with HIV and CD4 cell counts >200 cells/microL. However, we would recommend referral to an Infectious Diseases specialist when it comes to live vaccines.

6. Admitting a patient on ART (Antiretroviral Therapy)

Joya: Thank you, for this detailed approach. Now, let's consider a different scenario: what if we admit someone who is already on antiretroviral therapy to the hospital for a condition that’s unrelated to HIV: What special considerations or precautions should we keep in mind regarding their medication regimen and overall HIV management during their hospital stay?

Dr. Yetmar: Continuity of ART is crucial to prevent viral resistance. It's important to determine the patient's regimen and adherence, check recent viral loads and CD4 counts, assess for signs of ART toxicity, and consult with infectious disease specialists. Communication with the patient's outpatient HIV provider ensures seamless care. Monitoring for potential drug interactions is essential, depending on the ART regimen. Some regimens include a pharmacologic booster – either ritonavir or cobicistat – and these have numerous drug-drug interactions. Ultimately, if a patient has an elevated viral load and decreased CD4 count, they may need evaluation for opportunistic infections. However, if they are virally suppressed with a normal CD4 count, then opportunistic infections would be unlikely, and they can be approach similarly to patients without HIV. 

Conclusion

Joya: Thank you Dr. Yetmar for this insightful discussion on HIV. It’s clear that with the right strategies and care, we can make a big difference in the lives of people living with HIV. As we wrap up this episode, what are the key takeaways you’d like our listeners to remember?

Dr. Yetmar: Main takeaways.

One key takeaway is that HIV screening is still underutilized, and we need to do a better job identifying individuals with HIV and connecting them to care. Also, with the advancements in antiretroviral therapy, we’re seeing that the major health issues for many patients are now related to metabolic or malignant complications, which makes primary care so important in managing these risks. And of course, prevention is critical, whether that’s promoting safe sexual practices or ensuring access to PrEP for those who are at risk.