HIV Flashcards
describe the immunology of HIV
The effects of HIV infection can be ascribed to the immune deficiency which develops in infected
patients. The virus has a surface glycoprotein (gp120) which binds to CD4 glycoprotein on the surface
of host cells. The most important target for the virus is the CD4 bearing lymphocyte (the T-helper
lympho- cytes) which the virus infects and subsequently destroys. The progressive destruction of the
CD4+ lymphocyte population corresponds to disease progression from HIV infection. The normal CD4
lymphocyte count is 500-1500 cells/mm3 and a patient is often asymptomatic from HIV infection until
the count has fallen to <200 cells/mm3. It is below this level that the patient’s risk of opportunistic
infection and tumour disease rises dramatically.
what does HIV infect?
HIV infects and destroys cells of the immune system especially the T-helper cells that are CD4+. CD4 receptors are not exclusive to lymphocytes, they are also present on the surface of macrophages and monocytes, cells in the brain, skin, and probably many other sites.
symptoms and signs of HIV progression
weight loss
lymphadenopathy
thrush
skin and oral disease
when should antivirals start in a patient with HIV?
CD4 lymphocyte cell count (normal 500-1500): Patients should be started on antivirals if CD4 count <350. Start PCP prophylaxis when count <200. The absolute cell count can fall in a healthy patient with an intercurrent infection so a “one off” cell count should not form the basis for treatment but rather a series of results.
describe how the viral load of HIV changes
initially high during acute infection
falls to a low level
rises again in later stages after on average 6-8 years
how can you quantify HIV viral load?
PCR to measure the number of RNA copies/ml blood
if the viral load of HIV is not suppressed to <40 copies/ml what should you do?
consider changing to a more potent/effective combination of antivirals
how can disease progression of HIV be influenced?
Age
HLA type
hx of seroconversion illness
theories of HIV infection
Evidence shows that co-factors are needed in the attachment of HIV to the CD4 cells (i.e., factors
similar to but distinct from the CD4 receptor). The chemokine receptor 5 (CCR-5) has been widely
studied. Patients with a mutation of both CCR-5 alleles appear to be very resistant to HIV infection.
HIV-infected patients who have a single CCR-5 allele mutant appear to have a slower rate of HIV
disease progression compared to others. CCR-5 is now a target for drug treatment.
a new class of antivirals are being developed called fusion inhibitors. what do these do?
block the attachment of the virus to the cell wall by blocking GP41
describe primary HIV infection
This is similar to glandular fever with rash, fever, pharyngitis and lymphadenopathy predominant. Some patients develop diarrhoea, meningitis or neuropathy. The illness is self-limiting, and blood should be taken early in its course (acute phase serum) and during the convalescent period to test for HIV antibody. The early sample will be antibody negative but antigen positive and the late sample will usually be antibody positive although 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. A severe or prolonged seroconversion illness is now recognised as a poor prognosticator which correlates with more rapid disease progression.
describe the process of reverse transcription
Once the virus penetrates the host cell it releases its RNA which must be converted to DNA to allow incorporation into the host genome. This process is known as reverse transcription and requires the enzyme reverse transcriptase.
give examples of reverse transcriptase inhibitors
zidovudine (AZT) didanosine (ddl) zalcitabine (ddC0 lamivudine (3TC) stavudine (d4T) abacavir
what other tissues do transcriptase inhibitors work on and what may this cause?
nucleoside analogues and therefore interfere with the function of many healthy host cells including marrow cells, as a consequence of which marrow toxicity is a frequently encountered adverse effect.
describe AZT
AZT was the first drug to be licensed for treatment of HIV infection. It remains useful despite increased
recognition of its limitations. It is particularly valuable in reducing transmission of infection from
mother to infant during pregnancy and in stopping the development of AIDS dementia (AZT
penetrates the blood brain barrier better than many other drugs of the same group).
what class of drugs are used in combination with nucleoside analogues in first line treatment?
non-nucleoside reverse transcriptase inhibitors
discuss the effect and side effects of non-nucleoside reverse transcriptase inhibitors
They act on the reverse transcriptase enzyme (at a different site from the nucleoside analogues) and are sometimes better tolerated than nucleoside analogues. The commonest side effect being vivid dreams/nightmares when taking the drug efavirenz.
name a non-nucleoside reverse transcriptase inhibitor
efavirenz
how do protease inhibitors work
inhibit the virus protease enzyme which cleaves polyproteins into proteins required for viral maturation
what are protease inhibitors usually used in combination with?
reverse transcriptase inhibitors
common side effect of protease inhibitors
raised cholesterol
name the drug classes used for treatment of HIV
nucleoside analogues non-nucleoside reverse transcriptase inhibitors protease inhibitors integrase inhibitors chemokine receptor antagonists fusion inhibits
how to integrase inhibitors work?
prevent viral DNA integrating into the CD4+ cell chromosome
give an example of an integrase inhibitor
graltegravir
how do chemokine receptor antagonists work?
interfering with the interaction between HIV and CCR5
how do fusion inhibitors work?
inhibiting the attachment of the virus to the host cell and thus preventing virus entry into cells and viral replication
currently, how do fusion inhibitors have to be given?
injection
discuss lipodystrophy in HIV
common side effect of some antiviral drugs e.g. AZT, stavudine. Loss of subcutaneous fat from face and limbs with redistribution to the breasts and abdomen significantly alters the patient’s appearance. Changing antiviral treatment can result in reversal of the lipodystrophy in some patients.
list adverse effects and what drugs they are associated with in the treatment of HIV
anaemia (AZT), pancreatitis (especially didanosine), neuropathy (especially stavudine) and hepatitis (especially nevirapine). Drug interactions are common with protease inhibitors and NNRTI’s. where serum drug levels may need to be monitored.
how can HIV be inactivated?
Heat
drying
many disinfectants
discuss the combined test for HIV and its implications
combined test for HIV antigen and HIV antibody. After exposure, this test can take up to three months to become positive. During this three month “window period”, an individual becomes highly infectious prior to the test becoming positive. 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 is the main use of measuring HIV viral load?
effectiveness of anti-retroviral therapy
how can you diagnose infection in babies of HIV mothers?
Tests for viral nucleic acid are also used to diagnose infection in babies of HIV infected women as passive
maternal antibody can persist for 15 months making diagnosis using the HIV antigen/antibody test difficult.
when should HIV PEP be started?
within 1 hr up to 72hrs
HIV and the skin
seborrheic dermatitis
molluscum contagiosum
shingles
recurrent genital, perianal or oral herpes
HIV and the mouth
oral hairy leukoplakia
oral candidaiasis
HIV and tumours
Kaposi’s sarcoma
B cell lymphoma
describe kaposi’s sarcoma
Originally (pre-AIDS) seen in sub-Saharan Africa where it was regarded as a slow growing tumour
unlikely to influence life-expectancy. KS is a vascular tumour arising from the endothelium. It develops
in a multifocal way and does not obviously spread through blood or lymphatics. The skin is the
commonest site, but it also frequently develops on the hard palate, in the gut or in the bronchi. Skin
lesions are unsightly but of little consequence usually. Patients may exsanguinate from the highly
vascular tumours in the gut or bronchi. The cause of KS is now known to be a herpes virus which has
been named the Kaposi’s-associated virus (KAV). This is probably transmitted sexually or through close
contact which may explain the fact that KS is rarely seen in drug users. Effective HIV-antiviral
treatment can often lead to resolution of cutaneous KS.
describe B-cell lymphomas in HIV
B-cell lymphomas can develop at many unusual (gut, soft tissue) sites but cerebral lymphoma is the
most commonly seen. The prognosis is extremely poor with patients usually intolerant of
chemotherapy. The best approach may be to use highly active antiretroviral therapy - to restore
immune function - in combination with chemotherapy.
describe WHO clinical stage 2 HIV
Moderate unexplained weight loss (<10% of
presumed or measured body weight)
Recurrent respiratory infections (sinusitis,
tonsillitis, otitis media, pharyngitis)
describe infections associated with WHO clinical stage 2 HIV
Herpes zoster Angular cheilitis Recurrent oral ulceration Popular pruritic eruptions Seborrheic dermatitis Fungal nail infections
describe WHO clinical stage 3 HIV
Unexplained weight loss (>10% of presumed or
measured body weight)
Unexplained chronic diarrhoea for > 1 month
Unexplained persistent fever for > 1 month (>
37.6 , intermittent or constant)
Persistent oral candidiasis
Oral hairy leukoplakia
Pulmonary tuberculosis (current)
describe infections associated with WHO clinical stage 3 HIV
Severe presumed bacterial infection (e.g.
pneumonia, empyema, pyomyositis, bone or
joint infection, meningitis, bacteraemia)
Acute necrotising ulcerative stomatitis, gingivitis
or periodontitis
Unexplained anaemia (Hb < 8g/dL)
Neutropenia (neutrophils < 500 cells/uL)
Chronic thrombocytopenia (platelets < 50,000
cells/uL)
describe WHO clinical stage 4 HIV
HIV wasting syndrome
Pneumocystitis pneumonia
Recurrent severe bacterial pneumonia
Chronic herpes simplex infection (orolabial,
genital, or anorectal site for > 1 month or
visceral herpes at any site)
Oesophageal candidiasis or candidiasis of
trachea, bronchi or lungs
Extrapulmonary Tb
Kaposi sarcoma
CMV infection (retinitis or infection of other
organs)
CNS toxoplasmosis
HIV encephalopathy
Cryptococcosis, extrapulmonary (including
meningitis)
Disseminated non-tuberculosis mycobacteria
infection
Progressive multifocal leukoencephalopathy
describe infections associated with WHO clinical stage 4 HIV
Candida of the trachea, bonchi or lungs
Chronic cryptosporidiosis (with diarrhoea)
Chronic isosporiasis
Disseminated mycosis (e.g. histoplasmosis,
coccidioidomycosis, penicilliosis)
Recurrent nontyphoidal salmonella bacteraemia
Lymphoma (cerebral or B-cell non-Hodgkin)
Invasive cervical carcinoma
Atypical disseminated leishmaniasis
Symptomatic HIV-associated nephropathy
Symptomatic HIV-associated cardiomyopathy
Reactivation of American trypanosomiasis
(meningoencephalitis or myocarditis)
how can HIV be spread?
sexual
injection drug misuse
blood products
organ transplants
