Immunology HIV - ProCEs3.proce.com/res/pdf/HIV101/HIV101pt2.pdfHIV‐Associated Nephropathy (HIVAN)1 • Most common cause of chronic kidney disease in HIV‐ infected individuals

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HIV 101:Overview of the Physiologic Impact of HIV and Its DiagnosisPart 2: Immunologic Impact of HIV and its Effects on the Body

Melissa Badowski, PharmD, BCPS, AAHIVPClinical Assistant Professor

University of Illinois at Chicago, College of Pharmacy

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Immunology of HIV

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Learning Objectives

At the conclusion of this presentation, participants will be able to:

1. Describe the basic immunology and impact of HIV‐1 and HIV‐2

2. Identify symptomatology associated with acute HIV infection

3. Explain effects of untreated HIV on the body

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HIV‐1 vs. HIV‐21

HIV‐1 HIV‐2

Higher infectivity Lower infectivity

Lower CD4 counts Higher CD4 counts

Higher viral loads Lower viral loads

Shorter asymptomatic phase Prolonged asymptomatic phase

Shorter time to AIDS progression Longer time to AIDS progression

HIV RNA used to monitor ART efficacy Cannot use HIV RNA levels to monitor ART efficacy in HIV‐2

CD4 recovery 50‐150 cells/mm3 annually Poor CD4 recovery

1. Clin Infect Dis 2011;52(6):780–787.

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55 Source: AIDSinfo 2016. https://aidsinfo.nih.gov/education-materials/fact-sheets/19/73/the-hiv-life-cycle

*Full‐sized version of infographic available at end of handout

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CD4 Count1

• Major indicator of immune function• Type of lymphocyte (T‐helper cells)• Most recent CD4 count is best predictor of disease

progression• CD4 count usually is the important consideration in

decision to start antiretroviral therapy (ART) • Recommended to offer treatment to ALL regardless of CD4 count• 500 – 1600 cells/mm3 = Normal Range• < 200 cells/mm3 = AIDS

– CD4 count may fluctuate from day to day and in response to stress, other infection(s), vaccination, fatigue, time of day

1. NIH Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV‐1‐infected adults and adolescents. Washington, DC: U.S. Department of Health and Human Services: AIDSInfo. Available at

http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf.

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CD4 Monitoring1

• Check at baseline and at least every 3‐6 months– During first 2 years of ART or if viremia develops while patient

on ART or CD4 count <300 cells/mm3

• If patient is clinically stable, may consider checking annually– After 2 years on ART with consistently suppressed viral load:

• CD4 300‐500 cells/mm3

• CD4 count > 500 cells/mm3: CD4 monitoring is optional

• Important in determining response to ART• Adequate response: CD4 increase 100‐150 cells/mm³ per year

1. NIH Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV‐1‐infected adults and adolescents. Washington, DC: U.S. Department of Health and Human Services: AIDSInfo. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf

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HIV RNA1

• Commonly referred to as viral load

• Detects HIV RNA in the serum (Tests for the virus, not the antibodies)

• Critical in determining response to ART– Goal of ART: HIV RNA below limit of detection (< 20 copies/mL)

– Undetectable viral load indicates virologic suppression

• RNA monitoring– Immediately prior to initiating therapy

– 2‐8 weeks after start or change of ART

– Check at baseline and at least every 6 months in stable patients


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Immune Response to HIV1

• Those with HIV will mount an effective immune response during the first few months of infection

• Over time this response will prove ineffective

– Cellular response

– Humoral response Production of HIV Antibodies


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HIV Progression1

• Infected CD4 (T‐cells) can be found in draining lymph nodes within 2 days and in plasma within 5 days

• A rapid rise in viremia occurs during acute infection– Occurs within days of the infection high viral load and

dissemination to organs and central nervous system (CNS)

• During the acute phase of infection, symptomatic illness characterized by maculopapular rash and flu‐like symptoms

• After this phase, viral load is markedly reduced and reaches steady‐state levels

1. Reitz MS, Gallo RC. Human Immunodeficiency Viruses. In Mandell: Bennett JC, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett’s: Principles and Practice of Infectious Disease, Vol 2, 8th ed. Philadelphia, PA: Elsevier; 2014:2054‐65.

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Clinical Signs and Symptoms of HIV

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Acute Infection1

• May be asymptomatic

• May become symptomatic 2‐4 weeks after infection– Fever, rash, lymphadenopathy, headache, diarrhea, oral ulcers, myalgia, or arthralgia

• Highly infectious during the acute infection phase and symptoms mimic other viral disease states


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Acute Infection Symptoms

Source: http://upload.wikimedia.org/wikipedia/commons/thumb/4/4a/Symptoms_of_acute_HIV_infection.png/860px‐Symptoms_of_acute_HIV_infection.png

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Primary HIV Infection1

• 1 to 3 months post‐transmission

• Peak in HIV RNA and decline in CD4 cells in the blood

– HIV can replicate during early infection without being controlled by the immune system

• Antibody development 3 to 12 weeks after infection

– Symptoms of seroconversion may develop and viral load decreases


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Clinical Latency1

• Viral symptoms disappear

• May last as long as 10 years without ART

• Post acute phase, CD4 count increases in the blood again

• HIV RNA in plasma declines


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AIDS1

• Acquired Immunodeficiency Syndrome

• After clinical latency period

• Rapid increase in HIV RNA

• Decline in CD4 counts – AIDS: CD4 < 200 cells/mm3

• Risk for opportunistic infections, cancer, and death


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AIDS Symptoms

Source: http://upload.wikimedia.org/wikipedia/commons/thumb/6/6b/Symptoms_of_AIDS.svg/496px‐Symptoms_of_AIDS.svg.png

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Clinical Progression of HIV to AIDS

Source: http://www.peripheries.org/wp‐content/uploads/2010/02/HIV_course.png

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Effects of Untreated HIV

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Effects of Untreated HIV on the Body1

• Without treatment immunosuppression leading to AIDS‐defining illnesses premature death

• Untreated HIV– Immune deficiency

– Direct effect on end organs

– Indirect effects of associated inflammation on these organs


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HIV‐Associated Nephropathy (HIVAN)1

• Most common cause of chronic kidney disease in HIV‐infected individuals end‐stage kidney disease

• May occur at any CD4 count

• Almost exclusively in black patients

• Ongoing viral replication appears to be directly involved in renal injury

• Uncommon in virologically suppressed patients

• ART in patients with HIVAN – Preserves renal function

– Prolongs survival


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Co‐infection with Hepatitis B (HBV) and/or Hepatitis C Virus (HCV)1

• HIV‐infected individuals have more rapid progression of hepatitis‐related liver disease

• ART may slow liver disease progression– Tenofovir, emtricitabine, and lamivudine active against HIV/HBV co‐infection

– Preservation or restoration of immune function – Reducing HIV‐related immune activation and inflammation

• HCV treatment outcomes improve when HIV replication is controlled or CD4 counts are increased

• Early initiation of HIV treatment in the co‐infected population may reduce the risk of liver disease progression


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HIV/AIDS and Cardiovascular Disease (CVD)1

• Major cause of morbidity and mortality

– One‐third of serious non‐AIDS conditions

– 10% of deaths

• Higher rates of CVD risk factors

– Smoking

– Dyslipidemia

– Exposure to certain ARVs

• ART associated with improved markers of inflammation, immune function, coagulation, and endothelial function

• Low CD4 nadir, on‐therapy CD4 count, and treatment interruption linked to CVD

• Early initiation of ART to reduce viral replication reduces CV events


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Malignancy1

• Chronic infection associated with increased AIDS‐defining malignancies and non‐AIDS‐defining malignancies

• Increased risk with CD4 < 350 ‐ 500 cells/mm3

• Protective effect of ART for HIV‐associated immunodeficiency

– Suppress viral replication

– Maintain CD4 count > 350‐500 cells/mm3


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Neurologic Impact1

• HIV detected in cerebrospinal fluid (CSF) of untreated patients, yet patients typically asymptomatic– May progress to HIV encephalitis or HIV‐associated dementia (HAD)

– More advanced systemic HIV infection severe CNS opportunistic infections (OIs) high morbidity and mortality

• Effective and early initiation of ART has significantly reduced neurological manifestations – Reduction of CSF HIV RNA to undetectable levels

• Potential for HIV‐associated polyneuropathy– Effective and early ART may reduce the effects


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Summary

• Although a cure does not exist, HIV is a retrovirus that is a controllable chronic disease state

• HIV can affect multiple organ systems throughout the body

Documents

Immunology HIV - ProCEs3.proce.com/res/pdf/HIV101/HIV101pt2.pdfHIV‐Associated Nephropathy (HIVAN)1 • Most common cause of chronic kidney disease in HIV‐ infected individuals