HIV/AIDS

Overview

Most patients with HIV are asymptomatic but some present with a flu-like illness in the weeks following exposure.

Transmission

HIV is spread parentally via infected body fluids (sexual contact, IV drug use); can also be spread vertically (mother-to-fetus).

• HIV transmission modes
  • Heterosexual contact (73%; more heterosexual males with HIV that have gotten infected via vertical transmission)
  • Other modes (9%)
  • Injecting drug users (8%)
  • Blood transfusion (7%)
  • Spouse infection (1%)
  • Men having sex with men (<1%)
  • Blood product infusion (<1)

HIV testing

HIV is diagnosed using HIV-1/-2 antigen and antibody immunoassays (4th gen antibody and antigen immunoassay). If the original test returns positive get HIV-1/HIV-2 antibody differentiation immunoassay. If differentiation is indeterminate negative get a HIV NAT test.

• Who should get tested for HIV?
  • Anyone who asks
  • Patients who have engaged in unprotected vaginal or anal sex with partners of unknown HIV status
  • Men who have sex with men (MSM; unprotected anal sex is very efficient at transmission)
  • HIV-negative partner in a serodiscordant relationship
  • Patients who use or have used IV drugs and needles
  • Patients who have been recently diagnosed with an STD
  • Pregnant women (as part of the ANC profile)
  • Patients with symptoms consistent with acute HIV syndrome

HIV natural progression

Natural progression from onset of symptoms to death is usually about 7 to 10 years. The CD4 count and viral load kind of have an inverse relationship

Prognosis: based on CD4 count

Infectivity: based on Viral load

Epidemiology

Up to 2 million new HIV infections occur worldwide.

Adult HIV prevalence throughout the world

HIV Incidence and Mortality in Africa

Acute HIV Syndrome

Occurs soon after infection. Difficult to diagnose. Corresponds with a rapid increase in viral load and a mild drop in CD4 count. Can be asymptomatic or Subclinical. Important to get a sexual history (recent unprotected sex) to rule out HIV in patients who present with mononucleosis/flu-like symptoms. Patients are particularly infectious during acute HIV infection because

• Symptoms
  • Fever
  • Malaise
  • Generalized lymphadenopathy
  • Maculopapular rash
• Investigations
  • HIV-1/-2 antigen and antibody immunoassay (PITC)
• Treatment
  • HAART if HIV+

Treating the Patient with HIV

Begin HAART upon diagnosis. Make sure patient gets their vaccinations and follow-up every 3-6 months.

• Investigations for newly diagnosed HIV patients
  • CD4 count
  • HIV Viral Load
  • HIV viral genotyping (resistance and susceptibility to meds)
  • Testing for TB, CMV, other STDs, Toxoplasma antibodies)
  • Pap smear (HIV increases the risk of cervical dysplasia)
  • CBC, BMP, TFT, LFT, Fasting lipid profile (HAART drugs can cause metabolic disturbances, some patients may have Hepatitis, so make sure kidneys and livers are functioning properly)
  • Ophthalmologic exam

Anti-retroviral therapy

Mainstay therapy in HIV. Very complicated. Before starting get HIV viral genotyping to determine the most effective drugs. Zidovudine was the first medication, first approved in 1986. 6. classes of ARVs exist.

1. Nucleoside reverse transcriptase inhibitors (NRTIs): Zidovudine (AZT), Tenofovir (TDF), Lamivudine (3TC), Emtricitabine, Abacavir (ABC), Didanosine, Zalcitabine, Stavudine
2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs): Delavirdine, Nevirapine, Efavirenz
3. Protease inhibitors (PIs): Indinavir, Saquinavir, Ritonavir, Lopinavir/Ritonavir, Nelfinavir, Amprenavir, Atazanavir
4. Integrase strand transfer inhibitors (INSTIs): Raltegravir, Doultegravir (DTG), Elvitegravir
5. Fusion inhibitors: Enfuvirtide
6. CCR5 antagonist: Maraviroc

Regimen (HAART)

The viral load should be cut in half in the first month and should ideally drop to undetectable within a couple of months CD4 count should also rise. Monitor patients for HIV metabolic syndrome.

• Antiretroviral regimen: Two NRTIs plus something else
  • Two NRTIs and an NNRTI
  • Two NRTIs and a PI
  • Two NRTIS and an INSTI

NRTIs

Block reverse transcriptase by competing for nucleotide binding. All NRTIs include lactic acidosis as a potential adverse effect

• Adverse effects
  • Zidovudine (AZT): Most commonly used; myelosuppression, GI upset
  • Tenofovir – few side effect; can cause renal failure (avoid in renally impaired patients)
  • Abacavir – Hypersensitivity reaction (get HLAB*5701), SOB, Myalgia
  • Didanosine – Peripheral neuropathy, Pancreatitis (linked to length of use)
  • Zalcitabine – Peripheral neuropathy, Pancreatitis (linked to length of use)
  • Stavudine – Peripheral neuropathy
  • Lamivudine – few severe adverse effects
  • Emtricitabine – few severe adverse effects

NNRTIs

Block reverse transcriptase allosterically.

• Adverse effects
  • Efavirenz: Avoid in pregnancy (women should get a PDT and birth control if on efavirenz); Most commonly used, Fatigue, Depression, Psychiatric disturbances
  • Nevirapine: Rash, hepatotoxicity
  • Delaviridine: Rash, hepatotoxicity

Protease Inhibitors

Blocks protease (which is responsible for maturing the HIV virion). The general adverse effect is lipodystrophy (liporedistribution, does it worse than other ARVs), lipid disturbances and GI upset)

Integrase Strand Transfer Inhibitor (INSTIs)

Blocks HIV integrase (integrates HIV DNA into the genome of the host CD cell). Has fewer adverse effects than other antivirals.

HIV in Pregnancy

HAART is recommended to ALL pregnant women as soon as they become pregnant (May continue current regimen). AVOID BREASTFEEDING (unless cannot get the formula)

• Efavirenz
  • Efavirenz is contraindicated during pregnancy (particularly in the first trimester – if you can find a better drug use it).
  • Women on efavirenz should be on contraception.
• When is vaginal delivery safe and recommended
  • Viral load less than 1000 (provided no OB/GYN contraindications)
• What to give baby after birth
  • Zidovudine (AZT) for at least 4-6 weeks
  • HAART if viral load >1000/mL OR was not taking ARVs

Post-exposure prophylaxis (PEP)

Recommended when there is exposure of mucous membranes or non-intact skin to high-risk body fluids of an HIV+ person. Must be commenced within 72 hours of exposure.

Involves HAART therapy for 4 weeks

Preferred regimen: tenofovir/emtricitabine along with an INSTI (raltegravir, dolutegravir)

• Criteria for post-exposure prophylaxis
  • Fluid must be exposed to non-intact skin or mucous membrane
  • It should be high-risk body fluid (eg. blood, semen, breast milk)
  • Should be from HIV positive person
• Which patient groups are regimens including Zidovudine reserved for?
  • Patients with renal dysfunction (eGFR <60) (cannot tolerate tenofovir)
  • Children < 2 years
• When to do HIV testing after post-exposure prophylaxis
  • 4-6 weeks
  • Again after 3 months
  • Whenever there are symptoms of acute HIV infection
• Additional investigations to get for the exposed patients
  • Investigations based on occupational and sexual exposure
    • HBV
    • HCV
  • Investigations for other STDs
    • VDRL
    • NAAT for gonorrhea and Chlamydia
  • Pregnancy test

Pre-exposure prophylaxis (PrEP)

PrEP is an FDA-approved, evidence-based means to prevent new infections among those a risk (reduces the risk of HIV transmission by up to 90%). Strict adherence is necessary for maximal effect.

Tenofovir/emtricitabine 300mg/200mg PO taken once daily

• Who is a candidate for PrEP?
  • HIV-negative patients in a sexually active serodiscordant relationship
  • Men who have sex with men (MSM) and transgender women who:
    • Have had sex without a condom in the past six months
    • Have had any STDs in the past six months
    • Does not regularly use condoms during sex and has sex with people of unknown HIV status who are at risk of contracting HIV
  • Anyone who has injected illicit drugs in the last six months shared recreational drug injection equipment with other drug users in the past six months or has been in treatment for injection drug use in the past six months
• Who is not a candidate for PrEP?
  • HIV+ patients (HIV can become resistant to the NRTIs)
  • Patients with eGFR <60 (IDSA)
• Which patients should you give special consideration when receiving PrEP?
  • HBV+ patients: discontinuing PrEP may result in acute hepatitis flare
  • Pregnant women: possible risk of fetal bone issues and pregnancy loss; breastfeeding is not a contraindication to PrEP

Pre-treatment counseling and workup

Get a detailed history and workup before commencing PrEP. Keep in mind that patients may not volunteer risk factors for HIV (because of stigma)

• Sexual history
  • Sex with men, women, or both
  • Sexual practices (ie. oral, vaginal, anal)
  • HIV serostatus of partner(s) – serodiscordant couple
  • Number of partners
  • STD history
• Drug/Substance history
  • Types of recreational drugs used
  • Sharing needles or equipment
  • Injection into a shooting gallery (shooting gallery = place set up to inject drugs)
  • Use of non-parenteral drugs that decrease condom use
• Investigations
  • HIV-1/-2 antigen and antibody immunoassay
  • Serum creatinine level (U/E/Cs)
  • HBV panel (HBsAG, anti-HBc, anti-HBs)
  • Pregnancy test
• Important information for counseling
  • Drug takes several weeks to achieve optimal serum concentration (condoms necessary for 7 days before anal intercourse, and 21 days before vaginal intercourse)
  • Encourage continued use of safe-sex practices, stressing the role of PrEP as an additional safeguard
  • Educate the patient about the symptoms of acute HIV infection and lactic acidosis.

Treatment

Tenofovir (TDF)/emtricitabin (Truvada) 300mg/200m PO taken OD

• Adverse effects
  • Lactic acidosis (as with all NRTIs)
  • Renal toxicity (AKI, Fanconi syndrome – watch out for patients with risk factors for renal disease DM, Chronic HTN, Older age)
  • Hepatomegaly and steatosis (Rare, but can get jaundice, etc.)
  • Bone Mineral Density Loss (If older women, get a DEXA scan)
  • GI upset (resolves with continued use)

Follow-up

Patients should be seen one month after initiation, then three months, then every three months thereafter

• Every 3 months
  • Monitor adherence to meds (ask about side effects)
  • HIV screening
  • Routine screening for STDs regardless of symptoms
  • Pregnancy test
  • Serum creatinine (for patients with risk factors for renal disease)
• Every 6 months
  • Serum creatinine (all patients)
  • Urinalysis (patients with risk factors for renal disease)

Opportunistic Infections in HIV/AIDS

Any patient with a CD4 count <200 (or who develops any of these infections) will be considered to be in the state of AIDS.

Pneumocystis jiroveci Pneumonia (PCP)

Previously Pneumocystis carinii. A yeast-like, human-specific fungus that cannot be cultured in vivo.

• Symptoms
  • Dyspnea
  • Cough
  • Chest pain
  • Fever
  • Constitutional symptoms
• Investigations
  • Sputum smear: best initial
  • Bronchoalveolar Lavage: most accurate
• Treatment
  • TMP/SMX, OR
  • Clindamycin AND Primaquine OR
  • Pentamidine
  • Dapsone AND Trimethoprim (if allergic to SMX) OR,
  • Dapsone AND Trimetrexate (if allergic to SMX, add Leucovorin)
  • Atovaquone (if allergic to SMX) OR,
  • Adjunctive steroids (Prednisone)
• Prophylaxis
  • TMP/SMX OR,
  • Dapsone or Atovaquone

Toxoplasmosis

Toxoplasma gondii is a protozoa that takes refuge in the brain mucosa. Causes symptoms similar to brain abscess.

• Symptoms
  • Fever
  • Headache
  • Confusion
  • Focal neurological deficits (weakness, palsies, paralysis)
• Investigations
  • CT or MRI: ring-enhancing lesions
  • T.gondii serology: most accurate with a positive imaging test
• Treatment
  • Pyrimethamine AND sulfadiazine
  • Pyrimethamine AND clindamycin (if patient has sulfur allergy)
• Prophylaxis
  • TMP/SMX
  • Dapsone AND Atovaquone

Cryptococcal Meningitis

Caused by Cryptococcus meningitidis. Has no prophylaxis

• Symptoms
  • Fever
  • Headache
  • Meningismus (Neck stiffness, Positive Kerning’s and Brudzinski’s sign)
  • Malaise
• Investigations
  • Head CT: before performing a lumbar puncture if patient has signs of raised intracranial pressure
  • Lumbar puncture for CSF analysis (and India ink test): best initial test
  • Serum CRAG (serology)
• Treatment
  • IV Amphotericin B for 10-14 days
  • Discharge on PO Fluconazole indefinitely

Mycobacterium Avium Complex

AKA Mycobacterium avium intracellular infection (MAI). Infection is similar to TB (primarily in the lungs but can disseminate to cause systemic infections). If a patient presents with symptoms and CD4 is in double digits treat presumptively for MAC.

• Symptoms
  • Productive cough
  • Fever
  • Night sweats
  • Fatigue
  • Diarrhea
  • Wasting
  • Pallor
• Investigations
  • Blood culuture: first diagnostic step
  • CBC: look for anemia
• Treatment
  • Clarithromycin AND ethambutol, may add rifabutin
• Prophylaxis
  • Azithromycin (if CD4 <100)

Cytomegalovirus (CMV) infections

Can present as CMV retinitis, CMV encephalitis, CMV esophagitis, or CMV colitis.

• Symptoms of retinitis
  • Change in vision
• Symptoms of encephalitis
  • Fever
  • Headache
  • Confusion
  • Altered mental status
  • Cranial nerve palsies (will not see focal deficits which are commonly seen in abscesses)
• Symptoms of esophagitis
  • Odynophagia
  • Chest pain
• Symptoms of colitis
  • Diarrhea (may be bloody)
  • Abdominal pain
  • Abdominal distension
  • Fever
• Investigations
  • Fundoscopy: for retinitis, yellow/white granular areas and hemorrhage
  • Lumbar puncture and CSF analysis: for encephalitis
  • Esophagogastroduodenoscopy (EGD) with biopsy: for esophagitis
  • Colonoscopy with biopsy: for colitis