HIV and AIDS Flashcards
Immunology of HIV infection
Virus has a surface glycoprotein which binds to CD4 glycoprotein on the surface of the host cells
The most important target for the virus is the CD4-bearing lymphocytes which the virus infects and subsequently destroys
What does the progressive destruction of CD4+ lymphocyte population correspond to?
Disease progression from HIV infection
What is the normal CD4 lymphocyte count?
500-1500 cells/mm^3
A patient is asymptomatic from HIV infection until the CD4 lymphocyte count is at what level?
< 200 cells/m^3 - below this level the patient’s risk of opportunistic infection and tumour disease rises dramatically
Patient signs and symptoms which indicate progression of HIV infection
Weight loss
Lymphadenopathy
Thrush
Skin and oral disease
When should patients with HIV be started on antivirals?
If CD4 < 350
When should PCP prophylaxis for HIV patients be started?
When CD4 < 200
Why should a one off cell count not form the basis for treatment of a patient with suspected HIV?
The absolute cell count can fall in a healthy patient with an intercurrent infection so treatment should be based on a series of results
What is the HIV viral load like?
Initially high during acute infection but usually falls to a low level, only rising again in the later stages of the disease - usually after 6-8 years of infection
How is the HIV viral load quantified?
Using PCR assay to measure the number of RNA copies per ml blood, also now used to measure patient response to antiviral treatment
When might a change in antivirals need to be considered?
If the viral load is not suppressed to < 40 copies per ml blood with current combination
What factors influence the disease progression of HIV?
Age
HLA type
History of seroconversion illness
Rate of progression of HIV if untreated
25% to early symptoms after 5 years and 50-70% to severe symptoms and opportunistic infections after 10 years if untreated
What receptor has been studied and is now a target for drug treatment of HIV?
Chemokine receptor 5 (CCR-5)
How do HIV infected patients with a single CCR-5 mutation respond to HIV infection compared to others?
Appear to have a slower rate of HIV disease progression
Presentation of primary HIV infection
Rash
Fever
Pharyngitis
Lymphadeopathy
Similar to glandular fever presentation
May also develop diarrhoea, meningitis or neuropathy
Self-limiting illness
Investigations to be done in primary HIV infection
Blood should be taken early in its course and during the convalescent period to test for HIV antibody
HIV viral load testing
What are the typical features of the early and late blood samples taken during a primary HIV infection?
Early sample will be antibody negative but antigen positive
Late sample will usually be antibody positive, but this may take up to three months to develop after the illness
HIV viral load testing is sufficiently sensitive to allow detection of
HIV during seroconversion and before the development of antibodies
Severe or prolonged seroconversion illness is recognised as
a poor prognosticator, correlating to more rapid disease progression
What are the two distinct virus types that HIV can be classified into, and which is more common?
HIV 1 and HIV 2
HIV 2 is much less common
Laboratory aspects of HIV infection
Causes persistent infection of cells
Easily inactivated by heat, drying and disinfectants
How do HIV 1 and 2 work?
Replicate via a DNA intermediate step using the viral enzyme reverse transcriptase
Conversion of RNA to DNA is an error-prone process
The errors cannot be corrected so result in virus diversity
GIV attachments to cells, reverse transcriptase and viral enzymes are all targets for HIV drugs
Main diagnostic method for determining whether a person is infected with HIV
combined test for HIV antigen and HIV antibody
How long after exposure might a combined antigen and antibody test take to become positive?
Up to 3 months
When should a person be considered infectious?
A person positive for HIV antigen/antibody should be considered infectious, but a negative HIV antigen/antibody test does not exclude infection if there may have been exposure in the previous 3 months
What does HIV viral load test do?
Quantifies the amount of the virus in the blood
When is the viral load high?
During the window period of infection when antibody is absent
Main use of HIV viral load
monitor effectiveness of antiretroviral therapy
When are tests for viral nucleic acid used?
To diagnose infection in babies of HIV-infected women, as the passive maternal antibody can persist for 15 months, making diagnosis using HIV antigen/antibody test difficult
What is involved in HIV resistance testing?
Looking for specific nucleic acid changes associated with resistance to the individual antiretroviral agents, aids decision on optimal therapy
What led to the description of the acquired immune deficiency syndrome (AIDS)?
In 1981, two previously very rare diseases in young men in the USA - pneumonia and Kaposi’s sarcoma - were noticed to be occurring in homosexual men, indicating that some sort of immunodeficiency was occurring in previously fit homosexual men
How may people are affected by HIV worldwide?
34 million, over 90% living in the developing world
How is HIV spread and what are its modes of transmission?
Spread by blood and body fluids
Modes of transmission;
sex
blood
mother-to-child
What is the commonest route of transmission of HIV in adults globally?
Heterosexual transmission
Modes of transmission relate directly to
prevention strategies for transmission
Also relate to groups at high risk for HIV
Examples of groups of people at high risk for HIV infection
Homosexual and bisexual men
IVDA
Those who have had sex with someone from a high prevalence area
Recipients of unscreened blood, blood products, tissue or organ (not in the UK)
Sexual contact with a person at risk
Child of HIV-infected mother
What are the risks of transmission of HIV to a healthcare worker following a significant percutaneous exposure, if no preventative action is taken?
Approximately 30% for a source positive for hepatitis B surface and E antigens
3% for a source positive for hepatitis C RNA
0.3% for a source positive for HIV
Are the risks of transmission greater following percutaneous or mucocutaneous exposure?
Mucocutaneous
What are the body fluids which should be handled with the same precaution as blood?
CSF Pleural, peritoneal and pericardial fluid Exudate or tissue fluid from burns or skin lesions Breast milk Amniotic fluid Vaginal secretions Semen Synovial fluid Any fluid containing visible blood Saliva
What immediate actions should be taken after blood/body fluid exposure?
Wash off splashes on skin with soap and running water
Encourage bleeding if skin has been broken
Wash out splashes in eyes, nose or mouth
Assessment of risk of virus transmission by someone other than the victim
Report the incident
Factors to be considered in risk assessment
Source of contamination
Extent of injury and how it was caused
Likelihood of hepatitis B or C or HIV in the source
Hepatitis B vaccination status of the victim
By what percentage can combination antiretroviral therapy decrease the risk of HIV infection?
80%
When should combination antiretroviral therapy be started following possible exposure to HIV?
Ideally within 1 hour, but still worthwhile up to 72 hours post-exposure, generally not recommended beyond 72 hours
Immunisations available for Hepatitis B
Active - recombinant
Passive - hepatitis B immunoglobulin
Immunisations available for hepatitis C
No vaccine, immunoglobulin or antiviral therapy for post-exposure prophylaxis available
When testing an identified source, when should post-exposure prophylaxis for HIV (if indicated) be started?
Before the test results
Early diagnosis and treatment of hepatitis C is associated with
higher likelihood of cure
Steps to avoiding exposure to blood-borne viruses in the health care setting
Use of good hygiene practices with regular hand washing
Cover existing wounds/skin lesions with waterproof dressings
Take simple protective measures to avoid contamination of person and clothing
Protect mucus membranes
Prevent puncture wounds, cuts and abrasions in presence of blood
Avoid sharps where possible
Use safe procedure for sharps handling and disposal
Clear up spillage of blood and body fluids promptly and disinfect contaminated surfaces
Dispose of contaminated waste safely
When should infected pregnant women be started on therapy?
Before the third trimester
When is the three drug combination adjusted?
If viral load is not adequately suppressed after 4-6 weeks of therapy
Current life expectancy of patients diagnosed at age 20 with CDF counts of;
< 100
100-200
> 200
< 100 - 52 years old
100-200 - 62 years old
> 200 - 70+ years old
How long is HIV treatment?
Lifelong
Once the virus penetrates the host cell, what happens?
It releases RNA which must be converted to DNA to allow incorporation into the host genome - this process is known as reverse transcriptase
What was the first group of drugs with activity against HIV?
Nucleoside reverse transcriptase inhibitors
- zidovudine
- didanosine
- zalcitabine
- lamivudine
- stavudine
- abacavir
What is the possible consequence of nucleoside reverse transcriptase inhibitors therapy?
They are nucleoside analogues which interfere with the function of many healthy host cells, including marrow cells, so marrow toxicity is a frequently encountered adverse effect
What was the first drug to be licensed for HIV treatment?
Zidovudine
When is zidovudine particularly useful?
In reducing transmission of infection from mother to infant during pregnancy and in stopping the development of AIDS dementia
In what time would patients taking zidovudine monotherapy develop resistant strains of HIV?
Within 18 months of starting treatment
What class of drugs is currently used as first line treatment in combination with nucleoside analogues?
Non-nucleoside reverse transcriptase inhibitors
How do non-nucleoside reverse transcriptase inhibitors work?
Act on the reverse transcriptase enzyme at a different site from the nucleoside analogues, sometimes better tolerated
What is the commonest side effect of the non-nucleoside reverse transcriptase inhibitor efavirenz?
Vivid dreams/nightmares
How do protease inhibitors work?
Inhibit the virus protease enzyme which cleaves polyproteins into proteins which are required for viral maturation - most potent group of antivirals
Why might the benefit of protease inhibitors be short-lived if given alone?
Resistance can develop
What is a possible side effect of protease inhibitor use?
Raised cholesterol levels occur in many patients taking this group of drugs, can have implications for development of premature vascular disease
How do integrase inhibitors work?
Act by preventing viral DNA integration into the CD4+ cell chromosome
Give an example of an integrase inhibitor
Raltegravir
How do chemokine receptor antagonists work?
Act by interfering with the interaction between HIV and CCR-5
How do fusion inhibitors work?
Inhibit the attachment of the virus to host cells, preventing virus entry into cells and viral replications, have to be administered as injections currently
When do most clinicians introduce three drugs in treatment of HIV?
When patients develop symptoms or laboratory markers which suggest disease progression
What current techniques and development should make it possible in the future to know which drugs the virus will respond to before treatment is started and which ones it is resistant to after treatment fails?
Laboratory techniques which allow the analysis of HIV for detection of the genetic mutations associated with resistance to reverse transcriptase inhibitors or protease inhibitors
Why is compliance important in HIV treatment?
Poor drug compliance and intermittent dosing will promote viral resistance.
Studies show that patients need to be > 95% compliant to achieve the optimum effect of their drug regime
Side effects of HIV drugs
Lipodystrophy (stavudine, AZT) Anaemia (AZT) Pancreatitis (esp didanosine) Neuropathy (esp stavudine) Hepatitis (esp nevirapine) Drug interactions (protease inhibitors and NNRTIs)
What is lipodystrophy?
Loss of subcutaneous fat from the face and limbs with redistribution to the breasts and abdomen, significantly altering the patient’s appearance
Side effects of nucleoside reverse transcriptase inhibitors
Marrow toxicity
Neuropathy
Lipodystrophy
Side effects of non-nucleoside reverse transcriptase inhibitors
Skin rashes
Hypersensitivity
Drug interactions
Side effects of protease inhibitors
Drug interaction
Diarrhoea
Lipodystrophy
Hyperlipidaemia
Side effects of integrase inhibitors
Rashes
Challenges of HIV care
Ageing population Osteoporosis Cognitive impairment Malignancy Cerebrovascular disease Renal impairment Ischaemic heart disease Diabetes mellitus
HIV prevention
Behaviour change Condoms Education Circumcision Treatment Pre-exposure prophylaxis Post-exposure prophylaxis for sexual exposure
Skin manifestations of HIV
Seborrheic dermatitis Molluscum contagiosum Shingles Recurrent varicella zoster virus Recurrent genital, perianal or oral herpes, often severe and extensive
Oral manifestations of HIV
Oral hairy leukoplakia (OHL)
Oral candidiasis
Tumours associated with HIV
Kaposi’s sarcoma
Lymphoma
Features of Kaposi’s sarcoma
Vascular tumour arising from endothelium
Develops in multifocal way
No obvious spread through blood or lymphatics
Skin is commonest site, also occurs on hard palate, in gut and in bronchi
Cause of Kaposi’s sarcoma
Herpes virus - Kaposi’s associated virus (KAV)
Transmission of KAV
Probably sexual or through close contact
Treatment of Kaposi’s sarcoma
Effective HIV antiviral treatment can often lead to resolution
Common sites of Lymphoma in HIV
B cell lymphoma at many unusual sites e.g. gut and soft tissue, cerebral lymphoma is the most commonly seen
Prognosis of lymphoma in HIV
Extremely poor as most patients are intolerant of chemotherapy, best approach may be to use highly active antiretroviral therapy in combination with chemotherapy
Features of primary HIV infection
Asymptomatic
Acute retroviral syndrome
Features of HIV clinical stage 1
Asymptomatic
Persistent generalised lymphadenopathy
Features of HIV clinical stage 2
Moderate unexplained weight loss, < 10% of presumed or measured body weight Recurrent RTI e.g. sinusitis, tonsillitis Herpes zoster infection Angular cheilitis Recurrent oral ulceration Papular pruritic eruptions Seborrheic dermatitis Fungal nail infections
Features of HIV clinical stage 3
Unexplained severe weight loss > 10% presumed or measured body weight
Unexplained chronic diarrhoea for > 1 month
Unexplained persistent fever for > 1 month
Persistent oral candidiasis
Oral hairy leukoplakia
Pulmonary tuberculosis
Severe presumed bacterial infections
Acute necrotising ulcerative stomatitis, gingivitis or periodontitis
Unexplained anaemia
Neutropenia
Chronic thrombocytopenia
Features of HIV clinical stage 4
HIV wasting syndrome Pneumocystis pneumonia Recurrent severe bacterial pneumonia Chronic HSV infection Oesophageal candidiasis Extrapulmonary TB Kaposi sarcoma Cytomegalovirus infection CNS toxoplasmosis HIV encephalopathy Cryptococcosis extrapulmonary Disseminated non-TB mycobacteria infection Progressive multifocal leukoencephalopathy Candida of the trachea, bronchi or lungs Chronic cryptosporidiosis Chronic isosporiasis Disseminated mycosis Recurrent non-typhoidal salmonella bacteraemia Lymphoma Invasive cervical carcinoma Atypical disseminated leishmaniasis Symptomatic HIV associated nephropathy/cardiomyopathy Reactivation of American trypanosomiasis
