Approaching HIV cases

Around 38 million people are living with HIV around the globe and as such chances are good that you will encounter a person at risk for or living with HIV in your future practice. Perhaps you will become an Infectious Diseases specialist and this will be your exciting daily work? But even if you enter the field of Emergency Medicine you will still need to know - is this a simple RSV infection or is this an HIV-associated opportunistic infection? If you intend to become a neurosurgeon - is this a meningioma or could it be toxoplasmosis? So let's get started.

Understanding diagnostic testing for, treatment of, and complications associated with HIV all requires some basic virology. To begin, who should be tested for HIV? The CDC.gov website (linked) has a helpful breakdown: who should be tested? along with some additional helpful fact sheets.

There are several generations of HIV tests available. Older (3rd generation) tests relied on host antibody production to the virus which takes some time (anywhere from 3 - 12 weeks). This is called a "window period" in which a person has been infected by HIV but does not yet have detectable antibody. ELISA tests were performed first due to their high sensitivity and then followed by a confirmatory Western blot that seeks to match protein bands of the HIV virus as outlined below.

Find the gp120 and gp41 proteins in the cartoon below. Newer (4th generation) tests also look for antigen from the viral capsid and shorten the window period down to a couple weeks. Find the capsid p24 core ag in the viral particle. If there is concern for an "acute" (< 3-4 weeks ago) HIV infection a nucleic acid test (HIV RNA test) is the test of choice.

There are exceptions to every rule, however generally ALL those infected with HIV should be treated with anti-retroviral therapy. Given non-adherence with therapy can result in genetic mutations limiting future treatment options, there are circumstances in which therapy may be temporarily held until a person is able to regularly take their medication. As we now are treating all HIV-infected patients, labeling someone as having "AIDS" does not often have clinical relevance and continues to have more stigma attached to it than using the term person with HIV virus infection. AIDS does indicate that the person does or once had a CD4+ T cell count of <200 (or <14%) or has had an "AIDS-defining illness" and these low CD4 cell counts are associated with opportunistic infections. CD4 cells have many important functions as Dr. Stephens outlines below, and thus, the lower they drop, the more risk of host opportunistic infection.

Diagnosing and treating AIDS-defining illnesses and opportunistic infections is challenging. The NIH site: hivinfo.nih.gov has a helpful guideline. Click on the link here or the link to the right, then click "guidelines." Now click on "Adult and Adolescent OI Prevention and Treatment Guidelines." Let's say we are concerned with toxoplasmosis. Click on "Toxo." What are the common clinical manifestations? Scroll down...how can we prevent disease with toxoplasmosis? Some important infections and CD4 count associations include:

There are also guidelines for initial evaluation of a "NEW" HIV patient (including which initial labs they will need and which labs should be used to follow them while on treatment) and for choosing anti-retroviral therapy for an adult or adolescent with HIV on the hivinfo.nih.gov site. Scroll back to the top of the the hivinfo webpage and click "guidelines" again and now select "Adult and Adolescent ARV Guidelines." Updates from the last version of the guidelines are described on the right side. On the left choose "What to start." This will give you a helpful reference of the panel's recommendations regarding initial combination regimens for the antiretroviral-naive patient. Find the Panel's recommended anti-retroviral medications within the viral life cycle below.

Given favorable side effect profile, ease of dosing regimen (one pill, once daily) biktarvy (biktegravir/tenofovir alafenamide/emtricitabine) and Triumeq (dolutegravir/abacavir/lamivudine) are 2 of the most popular combinations in regions with good access to care and medication resources/availability. Access to this relatively new medications is limited in developing areas and they may not be the best choice in situations in which compliance with therapy may be low.

Once the patient is on therapy, we monitor symptoms and side effects, the HIV viral load, chemistries and later the CD4 count. Guidelines for additional lab monitoring and evaluation in new patients as well as for those with opportunistic infections are also on the hivinfo site.

Gram positive laboratory algorithm

We are living in an exciting time in microbiology and clinical infectious diseases in which new methods are becoming more readily available and rapid to detect pathogens in clinical specimens. While PCR, 16S rDNA sequencing, microarrays and MALDI-TOF are becoming more readily available in more microbiology labs, as of "now", working through a gram positive lab algorithm is still necessary for boards and helpful in timely and skillful clinical practice.

The gram positive laboratory algorithm is like a map. We will run through this literally as a map...of KU SOM.

This is the KU SOM we will use as a reference. Obviously, most first year medical students walk the halls and think about gram positive bacteria.  

For your reference, here is a gram positive lab algorithm similar to that which you will find in First Aid and other board-prep and clinical micro references.

We will first run through this with a Prezi, linked here (need to unlock adobe flash in browser): Gram Positive Lab Algorithm

Finally, we will walk through it with an amateur video tour. While you are watching, think about where these gram positive bacteria live in a human host and which clinical diseases they may cause.

Gram Positive Lab Algorithm Video

Hepatitis B

Hepatitis B virus infection is transmitted via the "Bs" blood, birthing, bonking (sex) and this includes injection drug use (sharing needles/syringes), occupational needle stick, or much less commonly contact with open wounds of an infected person or sharing items with bodily fluids on them (razors, toothbrushes, etc).

When the virus enters the bloodstream it circulates and then primarily infects hepatocytes.

source: https://www.qiagen.com/us/shop/genes-and-pathways/pathway-details/?pwid=217

In the initial or immunotolerent phase there is limited immune response with minimal increase in liver transaminases (AST, ALT). The HBsAg shows up as early as week 4 and circulates during ACTIVE DISEASE. The HbeAg is next and indicates ability to infect others. Circulating HBV DNA will be high at this time and can be found with a nucleic acid amplification test as well. Around week 6 IgM anti-HBc and total anti-HBc start to rise. In immunocompetent adult hosts this phase is present during "incubation." If disease is acquired at birth this phase can last for decades - see chronic hepatitis below. Some individuals will then convert on their own to anti-HBe. The total anti-HBc peaks around week 20 and persists (which is how we know years later who at one time DID have the Hepatitis B virus).

In the immunoactive phase the HBV DNA declines and the immune system revs up leading to increased inflammation evident in rising liver transaminases. In the next phase (the third phase) if the individual did not already convert to anti-HBe they can after the immunoactive phase immune system surge. IgM to anti-HBc can go up here so it confuses whether or not THIS stage is brand-new infection (so often in clinical practice we don't use this particular Ab test). Most people during this third phase will have decline in HBV DNA as their immune system has attacked the virus, some will convert to HBsAg neg.

In the last phase (resolution) anti-HBs (aka HBsAb) develops (starts at variable times - as early as week 32 in few individuals) and we say they have "natural immunity." (i.e. their immune system developed immunity as a result of actual infection and not from a "man-made" vaccination).

To make it even more complicated, hepatitis B has a different pattern of Ab response when it behaves as a "chronic" infection (defined as surface Ag + > 6 months). Now you have the same pattern with initial HBsAg and Total + IgM anti-HBc but the surface Ag and HBeAg are present much longer (years) in an asymptomatic state (which may include normal liver transaminases). The IgM to anti-HBc still falls but the total core remains.

Seriously? Can this get any worse? Yes. Individuals with resolved hepatitis B viral infection who are: HBsAg negative, anti-HBs and anti-HBc positive and those with chronic active hepatitis B infection who are HBsAg positive but with negative circulating HBV DNA who get immunosuppressive therapies can REACTIVATE their hepatitis to an acute pattern which can progress to fulminant hepatitis and death. We should look for hepatitis B infection in these patients and they should be on a hepatitis B antiviral treatment before/while they are immunosuppressed.

Hepatitis B infection can be prevented with vaccination. As the first opportunity for infection of a newborn is at birth, this is when the vaccine is first recommended. The vaccine only gives you a positive surface antibody never a positive core. Think of this as to get to the CORE of immunity you have to have the actual virus.

UpToDate has some case examples if you find yourself still obsessed with Hepatitis B. Good luck!