Infectious Disease Compendium

Human immunodeficiency virus

Microbiology

A retrovirus. There is HIV 1and HIV 2. Interestingly, infection with HIV 2 leads to slower progression of HIV-1 (PubMed). Not that I am recommending coinfection as a treatment.

HIV-2 is less transmissible than HIV-1, progresses more slowly than does HIV-1 infection, lower viral loads and lower rates of viral evolution. It can progress to AIDS. When to consider HIV 2? Patients from West Africa and/or AIDS patients with an indeterminate or negative HIV as the tests may not pick it up.

HIV may be becoming more virulent and infectious with time as condoms and HAART make transmission less likely; it makes evolutionary sense. Currently, time from seroconversion to a given CD4 cell count is CD4 500: 1.19 years, CD4 350: 4.19 years, and, CD4 200: 7.93 years (PubMed).

Epidemiologic Risks

Blood exposure and sex. Curiously, some men who have sex with men may not admit to it (PubMed). Herpes, Trichomonas, smoking (PubMed) all increase the risk of acquiring HIV.

If the viral load is suppressed, there is still a small risk of transmission estimated as follows: if a couple that has 100 sexual encounters per year, the cumulative annual probability of HIV transmission is 0.0022 for female-to-male transmission, 0.0043 for male-to- female transmission, and 0.043 for male-to-male transmission (PubMed).

Another estimate of per act risk of transmission in the suppressed is 13:100 000 (PubMed).

As the log of the HIV goes up, the risk increases 2.9 times, while condoms decrease the risk (PubMed).

There are cases of spread of HIV spread when the viral load suppressed and 28% of HIV acquired in a committed relationship is not from the HIV positive partner. Shock! People are not faithful. So keep the safer sex practices going even if the viral load is low, although the chances are extremely low.

Syndromes

Acute HIV (PubMed): fevers, rash, sore throat with mouth ulcers, lymphadenopathy, atypical lymphs (around 10%), acute aseptic meningitis. CNS invasion is primary disease is common (PubMed).

AIDS.

HIV is now a chronic illness that will be managed in part by primary care providers; the guidelines are here.

Treatment

Post-exposure prophylaxis (CDC Guidelines)

Start as soon as possible (less than 36 hours, up to maybe 72 hours) and give for 28 days. Guidelines change often, so go to the CDC site.

Pre-exposure prophylaxis

There are a variety of studies that demonstrate pre-medicating patients can prevent acquisition of HIV in some populations; the pros and cons are nicely laid out in the NEJM. The CDC recommendations favor  tenofoviremtricitabine (Truvada)  (PubMed). The data currently suggests benefit in HIV discordant couples; and those at high risk what to do for those who like to party hearty without condoms or MSM is uncertain. It will decrease spread of HIV by at least 92% (CDC). Truvada is the current (2017) drug of choice in the US, but you need to know local resistance patterns. For example, resistant HIV is common in parts of the Caribbean (PubMed).

Opportunistic infections will be in AIDS section; this is for the treatment of HIV itself.

Treatment

ALWAYS get genotype before therapy, primary resistance in treatment naive patients is not uncommon (PubMed).

The goal is a undetectable viral load, even a little bit of detectable virus, if persistent, is associated with disease progression (PubMed).

The data kind of suggests that time to treat is when the diagnosis is made (PubMed), and the higher the CD4 at start of therapy, the better the outcome (PubMed). The Guidelines from the CDC can lag, probably get no benefit if the CD4's are > 500 (PubMed).

When to start:

Start therapy when the diagnosis is made (PubMed).

offer..." ART to all patients regardless of CD4 cell count...Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir)."

That probably includes acute HIV where the delay in progression lasts as long as the medications were taken (48 weeks) (PubMed).

Watch for the Immune Reconstitution Syndrome, which occurs in 20-30% of patients one to 6 months after starting HAART. As the immune system returns patients can get a marked inflammatory response to any of the OI's in the AIDS section. The OI's tend to be atypical and often localized eg: Cytomegalovirus retinitis and focal M. avium-intracellulari infections, and cryptococcoma (serum cryptococcal antigen can be negative).

What to Start:

Listen up. Or read. This is text.

What to start and what and when to change is beyond the scope of this guide and my ability to keep the changes up to date. I do not take care of HIV per se, just the complications.

Here are, at least, the drugs.

Nucleoside/Nucleotide Analogues (NRTIs)

abacavir

didanosine

emtricitabine

lamivudine

stavudine

tenofovir

zalcitabine

zidovudine

Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)

delavirdine

efavirenz

etravirine

nevirapine

Protease Inhibitors (PIs)

amprenavir

atazanavir

darunavir

fosamprenavir

indinavir

lopinavir

nelfinavir

ritonavir

saquinavir

tipranavir

Fixed-Dose Combination Antiretrovirals

Combivir (zidovudine/lamivudine) One bid.

Trizivir (zidovudine/lamivudine/abacavir) One bid.

Epzicon (abacavir/lamivudine). One a day.

Truvada (tenofoviremtricitabine). One a day.

Atripla (efavirenz/emtricitabine/tenofovir). One a day.

Fusion Inhibitors

enfuvirtide

Chemokine Coreceptor Antagonists

maraviroc

Regimen Two-drug regimens

tenofoviremtricitabine (Truvada): One tablet (300 mg of tenofovir with 200 mg of emtricitabine) daily.

zidovudine–lamivudine (Combivir): One tablet (300 mg of zidovudine with 150 mg of lamivudine) bid.

Three-drug regimens

ritonavir–lopinavir (Kaletra) PLUS either (tenofovir-emtricitabine or zidovudine–lamivudine): Two tablets (50 mg of ritonavir with 200 mg of lopinavir per tablet) twice daily, or four tablets once daily

ritonavir plus atazanavir PLUS either (tenofoviremtricitabine or zidovudinelamivudine)100 mg of ritonavir plus 300 mg of atazanavir once daily

ritonavir plus darunavir PLUS either (tenofoviremtricitabine or zidovudinelamivudine): 100 mg of ritonavir plus two tablets, each containing 400 mg of darunavir qd.

Notes

My career started with the HIV (association is not causality) and the most amazing thing is how HIV/AIDS went from a death sentience to an almost normal life expectancy.

"A 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population. Differences by sex, race, HIV transmission risk group, and CD4 count remain (PubMed)."

Everyone should have a genotype before initiation of therapy and a genotype or phenotype done before any changes are made.

Evaluation by HLA testing can predict abacavir hypersensitivity.

Zinc supplementation (12 mg of elemental zinc for women and 15 mg for men) will slow progression regardless of viral load and compliance (PubMed).

Pregnancy: transmission of the HIV from mother to child is down to 1 - 2 % with appropriate treatment (see CDC guidelines). Additional medications: 200-mg qd of high-selenium yeast (Selenomax, Nutrition 21 Inc) had better response to viral load and CD4 counts (PubMed).

For heterosexual transmission, circumcision leads to a decrease in acquisition rate by 60%, it's because the foreskin has an enormous number of cells at risk for HIV, most of any part of the body. So nice how Bishops in Africa, while against condoms, at least have no issues with circumcision. They didn't charge money, but they did take tips.

Treating concomitant HSV will delay progression of HIV in those not on HAART; use when patients is on HAART unknown. Valacyclovir is perhaps better than acyclovir (PubMed)21998479