Human immunodeficiency virus (HIV) infection: Clinical sciences

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Introduction0:00–1:05

Human immunodeficiency virus, or HIV for short, is a single-stranded RNA retrovirus that targets the body’s immune system.
HIV is transmitted by contact with infected body fluids, such as blood, semen, and vaginal fluids. There are two types of HIV: HIV-1 and HIV-2; but generally, when we talk about HIV infection, we usually mean HIV-1 because it's the most widespread.
Now, HIV causes immunosuppression by targeting and infecting CD4 T cells, which are a type of white blood cell that helps coordinate the immune response to infection.
The acute phase of HIV infection is called acute retroviral syndrome, after which the individual can be asymptomatic for as long as a couple of years.
However, without appropriate medical management, HIV infection can progress to acquired immunodeficiency syndrome, or AIDS.
Now, if your patient presents with chief concerns suggesting an HIV infection, first perform a focused history and physical examination.

History and physical exam1:05–3:04

These patients typically have nonspecific symptoms, such as fever, fatigue, night sweats and unintentional weight loss. Additionally, your patient might report myalgias, arthralgias, or gastrointestinal manifestations, like nausea, vomiting, and diarrhea.
Your patient could also report a sore throat. Other historical findings may include high-risk sexual behavior such as unprotected sexual activities or multiple sexual partners; intravenous substance use; or occupational risk factors such as accidental needlestick injury.
Physical examination might reveal a rash, lymphadenopathy, or signs of sexually transmitted infections, such as purulent urethral discharge or painful fluid-filled blisters around the genitals.
You might also find needle marks on the skin overlying veins in individuals who have used intravenous drugs. Finally, distinctive but rare manifestations of HIV infection include mucocutaneous ulcers, which typically affect oral and genital regions.
Here’s a clinical pearl! In some cases, patients with undiagnosed HIV infection may present with opportunistic infections like Pneumocystis jirovecii pneumonia, or opportunistic neoplasms, such as Kaposi sarcoma, which presents as dark, reddish-purple or brown skin lesions.
Unfortunately, these are also considered AIDS-defining illnesses, which occur at a CD4 count less than 200 per microliter.
So, if you encounter a patient with an opportunistic disease, without a known immunocompromising condition, remember to perform HIV testing!
With these findings, you should suspect an HIV infection, and order a combined HIV antibody and p24 antigen immunoassay.

HIV infection3:04–3:33

Here’s a clinical pearl to keep in mind! It’s also recommended to screen for HIV during pre-pregnancy planning and as early in pregnancy as possible.
Individuals with certain risk factors, such as more than one sexual partner, should be screened more often. Okay, first let’s focus on patients with a non-reactive HIV antibody and p24 antigen immunoassay.

Non-reactive findings - No exposure3:33–4:03

This means both HIV antibodies and p24 antigen were not detected. Your next step is to assess for HIV exposure within the past month.
If your patient reports no known recent HIV exposure, you can exclude HIV infection and consider an alternative diagnosis.
On the other hand, if your patient reports a known HIV exposure, order an HIV-1 nucleic acid test, or HIV-1 NAT for short, which detects levels of HIV-1 RNA in the blood.

Non-reactive findings - Exposure4:03–5:22

This test can help you rule out HIV infection because HIV antibodies and the p24 antigen can take up to 6 weeks to appear in the blood and be detected, while the NAT can usually detect HIV 10 to 33 days after exposure!
So, if the HIV-1 NAT is negative, you should consider an alternative diagnosis. However, if the HIV-1 NAT is positive, diagnose HIV-1 infection.
And here’s another clinical pearl! A negative HIV test doesn't always rule out HIV infection.
That’s because there’s a period of time, called a window period, between a person’s exposure to HIV and when a test can actually detect HIV.
This window period is different for each type of HIV test. So, if your patient reports a potential HIV exposure and their test is negative, they should be tested again to confirm the negative test result!

Management5:22–7:12

Once you diagnose HIV-1 infection, proceed with management, which primarily relies on antiretroviral therapy or ART for short, which is aimed at suppressing viral replication until the virus is undetectable and can’t be transmitted.
ART uses a combination of at least 3 different medications that will target different parts of the HIV life cycle. A typical regimen may include two nucleoside reverse transcriptase inhibitors like tenofovir alafenamide and emtricitabine combined with an integrase strand transfer inhibitor, like dolutegravir.
Next, if needed, remember to treat any other bloodborne infection that your patient might have, like hepatitis B and C, as well as other STIs, such as gonorrhea and herpes simplex.
Next, encourage annual vaccinations against influenza and COVID, as well as vaccinations against pneumococcal disease, Hepatitis B, and HPV.
Finally, remember to provide patient education about medication adherence and safe sex practices, as well as contraception and family planning for biologically female individuals of childbearing age.
Here’s another clinical pearl to keep in mind! Before starting treatment, obtain baseline HIV-1 RNA levels to determine the viral load and assess the CD4 count.
Additionally, consider performing genotype resistance testing to detect mutations in the reverse transcriptase and protease genes.
This way you can assess the infection severity and tailor treatment to the individual's specific needs. Now, let's go back and take a look at patients with a reactive HIV antibody and p24 antigen immunoassay, which indicates a possible presence of either HIV antibodies or the p24 antigen.

HIV antibody/p24 antigen reactive7:12–7:39

At this point, you still can’t make a definitive diagnosis, so your next step is to order an HIV-1 and HIV-2 differentiation immunoassay.
If the test is positive for HIV-1 antibodies, diagnose HIV-1 infection and proceed with the same management, which primarily relies on antiretroviral therapy and treatment of co-existing infections.

HIV-1 Antibodies Detected7:39–7:58

Again, don’t forget vaccination and the importance of patient education. On the other hand, if the test is negative for HIV-1 antibodies or if the test is indeterminate, perform HIV-1 NAT testing to check for the presence of HIV-1 RNA in the blood.

HIV-1 Antibodies not Detected/Indeterminate7:58–8:47

If the HIV-1 NAT test is negative, consider an alternative diagnosis. However, if the test is positive, diagnose HIV-1 infection and proceed with management.
Here’s one last clinical pearl! The treatment of HIV-2 is essentially the same as for HIV-1, with one exception.
Non-nucleoside reverse transcriptase inhibitors should not be used in HIV-2 treatment, as the HIV-2 virus is resistant to this class of medications.

Review8:47–10:00

Alright as a quick recap… HIV is a single-stranded RNA retrovirus that targets the body’s immune system. If you suspect an HIV infection, order a combined HIV antibody and p24 antigen immunoassay.
If non-reactive, but there is known recent exposure to HIV, obtain an HIV-1 NAT test. If the virus is detected, diagnose HIV-1 infection and begin management with antiretroviral therapy.
However, if your patient’s combined HIV antibody and p24 antigen immunoassay is reactive, order an HIV-1 and HIV-2 differentiation immunoassay.
If HIV-1 antibodies are detected, diagnose HIV-1 infection and begin management with antiretroviral therapy. On the other hand, if results are negative or indeterminate, order HIV-1 NAT testing; and if it is positive, diagnose an HIV-1 infection and start antiviral treatment.