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STD's are Americans leading health care problem second to what?
STD's are defined as?
Any disease that is spread by various sexual practices between sexual partners
Why have the # of cases of STD's increased since 1960?
- 1. Age of first sexual activity has declined
- 2. # of people at highest risk(15-25) has ^
- 3. # of sexual partners has ^
- 4. Methods of BC have changed from diaphragms and rubbers to BC pills and IUD's
List the agents of transmission.
- 1. bacteria
- 2. Chlamydia
- 3. viruses
- 4. fungi
- 5. protozoa
- 6. parasites
- 7. unidentified microorganisms
List Portals of entry of STD's.
- 1. mouth
- 2. genitalia
- 3. urinary meatus
- 4. rectum
- 5. skin
All STD's are more common in persons who have more than one sexual partner.
It is not uncommon for a person to be concurrently infected with more than one type of STD.
What are some manifestations of STD's in men and women that may be seen in terms of infection?
- 1. external genitalia
- 2. vaginal infections
- 3. infections that have systemic effects and genitourinary
What are the 3 general groups of STD's?
- 1. Infections of the External Genitalia
- 2. Vaginal Infections
- 3. Vaginal-Urogenital-Systemic Infections
What are the Infections of the External Genitalia?
- 1. HPV Human Papilloma Virus -Condylomata Acuminata
- 2. Genital Herpes
- 3. Molluscum contagiosum
- 4. Chancroid
What are the Vaginal Infections?
- 1. Candidiasis
- 2. Trichomoniasis
- 3. Bacterial Vaginosis (nonspecific Vaginitis)
What are the Vaginal-Urogenital-Systemic Infections?
- 1. Chlamydial Infections
- 2. gonorrhea
- 3. Syphilis
What is gonorrhea?
A bacterial infection of the sex organs, in most cases only the urethra in men and cervix in women.
Gonorrhea- most epidemics have been associated with military conflicts especially WWI and WWII.
When _____ became available, gonorrhea incidence fell to low levels.
In 1960's gonorrhea increased frequency once more due to.
- 1. Changing social values
- 2. Introduction of birh control pills
- 3. Increasing resistance to penicillin
- 4. Large numbers of military personnel in Southeast Asia,
- Iraq, and Afganistan
How many gonococcal infections are reported each year to the Public Health Service?
One million, but the true incidence of infections is likely to be significantly higher in as much as many sexually transmitted infections go unreported.
Gonorrhea, disease transmission occurs through?
Contact with exudates from the mucous membranes of infected persons, usually by direct contract.
Gonorrhea, after direct contract what does the gonococcus attach to?
It attaches and penetrates columnar epithelium and produces a patchy inflammatory response in the submucosal layer with a polymorphonuclear exudate.
Direct extension of the infection with gonococci occurs by way of _________ system.
Once gonococcal infection has spread to other area, localized infection occurs and may result in the formation of _______ and _________.
Cysts and abscesses
Gonorrhea, Purulent exudate containing the organism causes damage to _______, and fibrous tissue replaces ______ tissue.
Gonorrhea, hardened, fibrous tissue may result in _________ and _________ of the _____, _______, or
Scarring, narrowing, urethra, epididymis, oviducts
What is gonorrhea's incubation period?
in males 3-7 days, in females it is variale and is usuallu asymptomatic until complications begin.
Gonorrhea of the male urethra
causes a thick whitish-yellow discharge of pus from the penis and a mild to intense burning which maybe constant or only during urination.
Gonorrhea, __% of infected males are asymptomatic.
If untreated men, gonorrhea may develop into:
- 1. Inflammation of the prostate gland
- 2. Scarring of the urethra
- 3. Intense irritation and swelling of the testicles
- 4. Sterility, crippling, blindness and death
Cervical gonorrhea, ____% of women have mild or no symptoms, and the disease goes unnoticed.
What are 2 symptoms of cervical gonorrhea?
Occasionally a vaginal discharge and buring sensation durning urination occur.
3 Complications from cervical gonorrhea are...
- 1. Pelvic infammatory Disease PID)
- 2. Sterility
- 3. Ectopic pregnancy
There are thought to be _____ symptomatic female carriers. Of these ___% will develop major complications.
All sexually active females should have ______, ______, and ________ yearly.
pap test or thin prep, and a gonorrhea test
Other types of gonorrhea include _____, _____, and _____.
rectal, throat, and gonorrhea in babies and children.
Most cases can completely and quickly be cured without damage if diagnosed and treated soon after infection. However resistant strains have developed and no body immunity develops so re-infection can occur repeatedly.
In 1995, 31.6% of gonorrhea patients were resistant to both penicillin and tetracycline. What does this cause the CDC to recommend?
That all gonococcal infections be treated as if the organism were antibiotic resistant and that chlamydia infection coexisted with the gonorrhea.
What is Chlamydia?
Chlamydia trachomatis organism has some features of a virus and some of a bacteria.
Chlamydia organism is...
- 1. Larger and more complex than a virus
- 2. Has to live inside other cells to reproduce
- 3. Like bacteria, chlamydia can be killed by antibiotics
There are numerous types of chlamydia. What are they?
Trachoma types A, B, Ba, & C
Trachoma types A, B, Ba, & C cause what and why?
Eye infections that result in a million cases of blindness world wide each year, mostly in Asia and Africa. It is spread by unsanitary living conditions. When it appears in developed countries, it is usually sexually transmitted.
_____ is the most common STD in the US and often occurs with _______. They affect organs, symptoms, and complications are similar.
Chlamydia incubation period. Males? Females?
Males is 1-3 weeks. Often symptoms appear after being treated for gonorrhea. Infections remain asymptomatic but infectious for years. Urethritis is one of the most common complications between day 5-21 after sexual activity with a carrier.
Chlamydia symptoms in men
mucus discharge and pain on urination. Without treatment infection may lead to infection of prostate gland, epididymis, tesicles, and sterility.
Chlamydia symptoms in women
Most women have no symptoms. Many have mild inflammation of the cervix, which goes unnoticed. Complication is usually PID.
What symptoms do babies have and how is it transmitted to them?
- Eye (opthalmia neonatorum)
- ear or lung infections. It is transmitted during the birth canal passage.
What is Non-Gonococcal Urethritis (NGU)?
Inflammation or infection of the urethra from causes other than gonorrhea most often by stains of C. trachomatis that act on columnar epithelium in a manner similar to that of the gonococcus.
NGU is thought to be more frequent than ______, symptoms are similar but milder, onset less abrupt, and less mucus discharge.
What are NGU symptoms in men? Women?
- Men- pain with urination and frequent urination.
- Women- symptoms are less specific and the term "acute urethral syndrom" has been introduced to describe NGU- like syndrome in females.
What is Pelvic Inflammatory Disease (PID)?
An inflammation of the fallopian tubes, which may extend outside the pelvic area and involve the abdomen.
What is the frequency of PID?
more than 1 million cases /year, 200,000 of which require hospitalization.
___% of gynecological visits are PID related?
What is the estimated annual total cost associated with treating acute pelvic inflammatory disease associated with STD's in women ?
over $3 billion
Besides personal cost to the individual experiencing an STD what are some other things a person may experience? 3
- 1. Pain
- 2. disfigurement
- 3. permanent steritlity
What are causes of PID? 3
- 1. Most common complication of gonorrhea or chlamydia
- 2. other organisms not sexually transmitted
- 3. IUD's for birth control
What are symptoms of PID? 6
- 1. low abdominal pain
- 2. increased menstrual cramping
- 3. low back pain
- 4. pain while having sex
- 5. vaginal discharge
- 6. fever
How is PID diagnosed?
PID diagnosis is difficult to make, numerous other problems have similar symptoms.
What % of patients with PID are incorrectly diagnosed?
What are some compications of PID? 4
- 1. infertility caused by scarring of the fallopian tubes (100,000/yr)
- 2. tubal pregnancy- may rupture tube causing life-
- threatening bleeding
- 3. abscesses in abdomen, persistent pin
- 4. hysterectomy (premature) and depression
What is Hepatitis?
An inflammation of the liver and may be caused by toxic chemicals, alcohol or viral infections, which are often sexually transmitted.
What are four common types of viral hepatitis?
- Hepatitis A- formerly called "infectious hepaitis"
- Hepatitis B- formerly called "serum hepatitis"
- Hepatitis D- "delta hepatitis" found only in combination with
- Hepatitis C- which can not be "traked to other hepatitis's
What is the Prevalence of Hepatitis?
more than 500,000 Americans per year become newly infected with some form of viral hepatitis. Of these 200,000 develop hepatitis B, and a rapidly increasing number are developing hepatitis C.
Where is Hepatitis A found in the body?
excreted in the feces, not in other body fluids.
How is Hepatitis A spread? 4
- 1. direct contact
- 2. food handlers
- 3. drinking water
- 4. food- raw or steamed clams, oysters or mussels
Where is hepatitis found in the body?
The virus is found in all body fluids of infected persons- blood, semen, saliva and urine.
How is Hepatitis B spread? 5
- 1. intimate contact with infected persons
- 2. exposure to body fluids
- 3. piercing of skin by contaminated instruments used for
- tattooing, ear piercing, acupuncture, dental or medical
- 4. shared illicit drug equipment
- 5. sexual transmission- contaminated body fluids in
- contact with mucous membranes or tiny breaks in
What is different about Hepatitis D?
Cannot initate an infection by itself, but acts together with hepatitis B to produce a disease more severe than that caused by B alone.
How is Hepatitis D spread?
- It is spread the same as hepatits B,
- 1. intimate contact with infected persons
- 2. exposure to body fluids
- 3. piercing of skin by contaminated instruments used for tattooing, ear piercing, acupuncture, dental or
- medical procedures
- 4. shared illicit drug equipment
- 5. sexual transmission- contaminated body fluids in
- contact with mucous membranes or tiny breaks in skin
What is hepatits C (non-A, non-B)?
refers to cases that cannot be traced to A, B or D Viruses. There may be more than one agent responsible.
How is hepatitis C transmitted?
Major source of transmission is transfused blood, although it may also be spread by close contact, especially sexual contact. There was no test for this until 1991
What are symptoms for Hepatitis? 8
- 1. low grade fever
- 2. tired, malaise
- 3. nausea, diarrhea, vomitting
- 4. distate for cigarettes
- 5. urine turns dark
- 6. feces pale colored
- 7. skin becomes yellow, juandice
- 8. liver swells and become tender
What are treatments of Hepatitis?
- There is no specific treaement for hepatitis other than:
- bed rest, avoidance of drugs, alcohol and fats, inactivity and perhaps gamma globulin and isolation.
Why is it so important to prevent Hepatitis?
Since there is no treatment, prevention becomes very important.
Prevention for Hepatits A
Family members may receive gamma globulin
Prevention for Hepatits B
- Exposed persons may be given a blood product with a high concentration of protective hepatitis B antibody (hepatitis B immune globulin HBIG).
- Hepatitis B vaccine may be considered for long-term prevention.
What does AIDS stand for?
Acquired immunodeficiency syndrome
When was AIDS recognized as a distinct clinical entity?
1981, when unusual clusters of cases of Kaposi's sarcoma and Pneumocystis carinii pneumonia were observed in California and New York.
HIV causative agent was described in ____, andserologic test for HIV antibodies were available in ____.
1983 and 1985
Through the end of 2000, more than ______ people have been diagnosed with AIDS in the US, and more than _____ are known to be dead.
774,000 and 1/2
Approximately _______ new cases of HIV-1 infection occur daily.
Nearly 3/4th of the world's HIV-1 cases are found in ________.
Why are death rates rising in most countries? 3
- 1. continued unchecked heterosexual and vertical
- transmission of HIV
- 2. poor health maintenance support for infected
- 3. lack of access of ART (antiretroviral therapy)
AIDS is the world's ____ most common cause of _____ and the world's most _______ infectious disease.
fourth, death, deadly
What is the origin and spread of the HIV epidemic?
The origin of HIV has been traced to a subspecies of chimpanzee native to west central Afric. The virus probably jumped to humans through bites and exposure to blood in the hunting and dressing of chimpanzees approximately 70 years ago.
What are three routes of human transmission of HIV?
- 1. Sexual
- 2. Blood-borne
- 3. Maternal-infant
In most of the world, HIV infection is spread by _______
What is the most common route of HIV infection for women in the US?
Blood-borne transmission of HIV may occur with... 3
- 1. injection drug use
- 2. transfusion of infected blood or blood products
- 3. parenteral workplace exposure
Transmission from HIV-infected health care workers to patients appears to be exceeding ______.
Maternal-infant transmission of HIV can occur during? 3
- 1. gestation
- 2. the birth process
- 3. after the birth (through breast-feeding)
EBM is full of ____.
In the US, the proportion of AIDS cases in the major exposure groups remained stable for the first ___ years of the epidemic, but new trends have emerged.
Men who have sex with other men originally accounted for nearly ___% of AIDS cases. Now this group accounts for ~ ____% of the total.
________and ________ contacts of infected persons constitute a substantial proportion of the total number of AIDS cases in the US.
Intravenous drug users and heterosexual
In the year 2000, adult men accounted for ____% of newly reported HIV-1 infections, ___% of the new cases were in adult women, and ___% were in children less than 13 years of age.
68%, 31%, 1%
______ American women have been diagnosed with AIDS, and many thousands more may be infected but are yet unaware of their infection.
Which epidemiologic group rate of growth in AIDS cases is more rapid?
How many documented cases of health care workers in the US have been infected with HIV-1 in the work place?
56, the majority of documented transmissions have involved nurses and laboratory worker who were exposed to infected blood.
In the family of pathogenic retroviruses, HIV is a member of what group?
Lenti-virus (slow virus)
What are the two types of HIV?
- type 1- found worldwide and is the most common
- type 2- is restricted to West Africa and individual with ties to this geographic region.
HIV-2 is associated with what?
lower levels of viremia until late in the clinical course. Immunosuppression seems to take longer to develop, but the eventual complications associated with HIV-2 infection are similar to those of HIV-1.
Particles of HIV contain two copies of
the single-stranded ribonucleic acid genome packaged inside a capsid.
What factors complicate attempts to develop an effective vaccine? 3
- 1. Analysis of HIV-1 isolates from individuals patients has shown the genome differs substantially from person to person. (mutable)
- 2. Strains in individual patients appear to mutate with time
- 3. Patients may be infected with several HIV strains
HIV preferentially infects what type of cells?
CD4 cells, primarily T- helper/inducer lymphocytes, but it also infects other cells that carry the CD4 receptor, such as monocytes and macrophages.
In sexual transmission of HIV, what are the initial target cells?
Langerhan's cells, which are derived from the macrophage line and are found in genital and tonsillar submucosal tissues, also express CD4 on their surfaces.
What are thought to act as important cellular resevoirs for HIV, allowing viral infection to spread to the brain and other organs?
Once HIV is bound, either to CD4 lymphocytes or dendritic (macrophages) cells, it is transported to_______.
Regional lymphoid tissue.
With completion of the fusion of HIV to the CD4 receptor, the virus...
begins to replicate in the lymphoid tissue and later disseminated in the blood.
HIV can be detected in the blood appoximately ___ to ___ days after initial exposure, and extremely high levels of ______ are common early in infection.
7 to 10, viremia
When HIV binds to and enters a host cell, it produces a ________ copy of its RNA genome through its unique enzyme, __________.
deoxyribonucleic acid, reverse transcriptase
Viral DNA is incorporated into the host cell DNA and is reproduced, along with normal cellular components, every time the cell _______.
What is the estimated average total HIV production by short-lived activated lymphocytes?
10 billion virons daily
HIV contains ____ base pairs, and mutates at a rate of _____ per base pair per replication cycle; thus, every muatation at every position in the genome may occur numerous times each day.
104, 3.4 x 10-5
Why in HIV does viral eradicaiton not appear to be possible with current available therapeutic agents?
because of resistance and latency. (Can't get to the one burried in lymph nodes.)
The rate of progression of HIV infection varies greatly between individual due to?
Host genetics and variable viral virulence (extreme harmfulness-the capacity of a microorganism to cause disease)
___ to ____% of HIV-infected individual remain clinically well, with preseved immunologic function, for more than ___ years after infection.
What do you call people infected with HIV that are clinically well, with preserved immunologic function?
long-term non progressors
Up to 10% of infected individual progress to AIDS within ___ years of ________.
The majority of infected individual, however, there is progressive loss of ____ _________ in the 8 to 10 years after initial infection because of the ________ _____ of viral reproduction.
CD4 lymphocytes, cytopathic effect
It is postulated that at some point in the infection an event such as _____-_____ viral infection may trigger rapid HIV production and subsequent development of severe ___________.
Clinical manifestations of HIV-1 infection are related to its devastating effect on the immune system, primarily owing to a selective infection of ________________.
Immunosuppression in HIV infection is due to both __________ and _________ defects in _____________________.
quantitative and qualitative, CD4 T lymphocytes
Several studies have demonstrated that lymphoid organs represent the major anatomic sites for the ....
establishment and propagation of HIV infection.
(HIV) What do measurements of peripheral blood viral load reflect?
Only a portion of the total viral burden in infected individuals
What effectively traps HIV infected cells until the latest stages of infection?
Lymph nodes (it can't kill them, it just holds them)
Progressive loss of _________ are the cardinal manifestation of HIV infection?
CD4 T lymphocytes
Declining CD4 T lymphoctye counts are predictive of complications of HIV infection.
T lymphocyte counts of <200 cells per micro liter of blood (normal 400-1100 cell/micoliter), are associated with the development of __________ _______.
Opportunistic infections (micro organisms that exist symbiosis)
Where has HIV been isolated? 8
- 1. Blood
- 2. semen
- 3. vaginal secretions
- 4. breast milk
- 5. saliva
- 6. urine
- 7. CSF
- 8. tears
What two body fluids have the highest concentrations of HIV?
Blood and semen
What are the primary modes of spread for HIV? 4
- 1. sexual contact
- 2. IV drug use
- 3. perinatal exposure
- 4. transfusion
What is the % risk of perinatal transmission of HIV infection?
When can transmission occur perinatally? (HIV)
during gestation and birth process
The risk of perinatal transmission increases with higher maternal viral load levels.
What is the average risk of HIV seroconversion when percutaneous exposure occurs?
- Studies have demonstrated that HIV is not routinely spread through casual household contacts with an infected individual.
HIV enters through circulation of ______, then is carried to regional ______ _____.
mucosa, lymph nodes
What is one of the reasons for the abrupt decline in CD4 T lymphocytes in acute infections (HIV)?
activated CD4 cells accumulate in infected HIV lymph nodes.
What leads to lymphadenopathy?
intense viremia and multiple infected lymph nodes
What is now recognized as primary HIV infection or acute retroviral syndrome, which develops in more than 50% of HIV infected persons?
an infectious mononucleosis like syndrome
An infectious mononucleosis like syndrome is observed when _____ and how does it resolve?
2-6 weeks after exposure, it resolves spontaneously
What is rapid disease progression of HIV associated with? 3
- 1. Syncytial-inducing HIV-1
- 2. Low lymphocyte function
- 3. certain human leukocyte antigen types in infected individuals
Some experts advocate for early initiation of ___ for individuals with the acute retroviral syndrome and those who are within 6 months of seroconversion.
ART (antiretroviral therapy)
Why do some experts advocate early initiation of ART? 6
- such intervention may reduce
- 1. the magnitude of viral dissemination
- 2. the severity of acute infection
- 3. the rate of disease progression
- 4. viral mutation
- 5. possibly viral transmission
- 6. may also preserve immune function
Has the long-term clinical benefit of treatment immediately after seroconversion of HIV been demostrated?
No, once therapy is initiated, most physicians would continue it indefinitely. (doesn't seem to change the course, should you wait or start immediately?)
Most HIV-infected individuals look and feel ___, so recognition of patients with early HIV infection is potentially a challenge for primary care physicians.
Recognition of HIV infection (5)
- 1. History of STD's
- 2. women with recurrent vaginal candidiasis or carcinoma of the cervix
- 3. young people how have more than one episode of shingles
- 4. severe or recurrent HSV infections
- 5. certain dermatologic disorders including seborrheic dermatitis, psoriasis, warts, and molluscum contagiosum
____ greatly reduces HIV transmission to the fetus, all pregnant women should be screened for HIV and treated if they are infected.
ART (antiretroviral therapy)
When a patient is evaluated with idiopathic thrombocytopenia and generalized lymphadenopathy, what testing should be preformed? (bruising and enlargement of lymph nodes
Within 2 months of HIV infection in individuals what is detectable?
antibody to HIV, few patients take up to 6 months to seroconvert
What is ELISA? Can it have a false-negative result>
enzyme-linked immunosorbent assay, yes, <1% (usually in individuals who are in an early stage of infection
ELISA results should not be reported to patients until they have been confirmed by____________.
Western blot or another confirmatory test.
What are some causes of false-negative ELISA results? 4
- 1. multiparity
- 2. multiple blood transfusions
- 3. infections
- 4. autoimmune diseases
The CDC classification system for AIDS was modified in ____ to include _________________ count.
1993, CD4 T-lymphocyte count, as well as various clinical conditions associated with HIV infection.
The introduction of combination ART has significantly decreased the ________ and ________ associated with HIV infection.
morbidity and mortality
In 1987, ZDV (zidovudine) was introduced as the first antiviral agent with in vivo and in vitro activity against _____.
In 1990, NRTIs (nucleoside reverse transcriptase inhibitors) became available.
antiretroviral agents were used as sequential monotherapy or in two-drug combinations.
In 1996, protease inhibitors became available and ushered in the era of combination ART, also referred to as ________ _____ ______ ______.
highly active antiretroviral therapy (HAART)
Because of the new therapies introduced from 1987-1996 for HIV the patients ....
- 1. live longer lives with fewer infections
- 2. d/t the cost, in terms of direct expense and tx side effects, affects the overall health benefits of newer therapies.
The goals of ART are (4)
- 1. reduction in morbidity and mortality of HIV infection
- 2. improvement in quality of life
- 3. complete supperssion of HIV viral load for as long as possible
- 4. improvement of immunologic function
What do current drugs do for HIV?
they only prevent infection of new cells, but do not eradicate the virus from cells already infected.
What is the strategy drug therapy for HIV?
to continue HAART until infected cells have died and to block new rounds of viral replication.
What are the currently 3 classes of drugs available for the treatment of HIV infections?
- 1. Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
- 2. Protease Inhibitors
- 3. Nonnucleoside Reverse Transcriptase Inhibitors
ZDV the first antiretroviral agent is the prototype drug for ______.
NRTIs are nucleoside analogs that act at an early stage of viral replication by
competitively binding to the HIV reverse transcriptase enzyme. NRTIs act as chain terminators for HIV reverse transcriptase where they are incorporated into the elongating strand of viral DNA
NRTIs are classified as _________ _________ or __________ _________.
thymidine analogs ore nonthymidine analogs
NRTIs are ineffective as monotherapy and are used in combination with ________, ________, and _________ ___________.
other NRTIs, NNRTIs, and protease inhibitors
What are some side effects of NRTIs? 6
- 1. peripheral neuropathy is significant toxicity for ddI,
- d4T, and ddC
- 2. pancreatitis is an important toxicity of many NRTIs
- (from asymptomatic elevations in pancreatic enzymes
- to life-threatening pancreatitis
- 3. hypersensitivity syndrome in 3-5% of patients
- 4. mitochondrial toxicity
- 5. lipodystrophy
- 6. changes in body morphology
NNRTIs also target
reverse transcriptase enzyme but structurally are not related to naturally occurring nucleosides.
NNRTIs act by binding noncompetitively with
viral reverse transcriptase.
As a class, NNRTIs have an intermediate potency against HIV in acutely infected cells and
are synergistic with the NRTIs
There are several limitations to the class of drugs NNRTIs, one of the most important is?
being the rapid development of drug resistance. (body tears it apart)
What are some side effects of NNRTIs? 4
- 1. are generally well tolerated and lack peripheral
- neuropathy associated with NRTIs
- 2. rash is the most common side effect
- 3. hepatic metabolism step and elevations in liver function
- test may occur, and at times severe
- 4. drug interactions with the protease inhibitors, usually
- requiring dose adjustments of the protease inhibitor
When do protease inhibitors act when used in HIV?
at a late phase in the replicative cycle of HIV.
Protease inhibitors inhibit the viral protease enzyme, resulting in the release of immature viral particles incapable of infecting other cells.
by this mechanism, protease inhibitors reduce the production of infectious virions from chronically infected host cells.
NRTIs and NNRTIs act primarily on
newly infected cells
As a class protease inhibitors represent
the most potent anti-HIV agents available, with the ability to decrease circulating HIV RNA levels by grater than 2 log 10 with an increase in CD4 lymphocyte counts in many instance.
Protease inhibitors are synergistic when used in combination with ________.
NRTIs, the drugs are well distributed in the lymph system and have no hematologic or neuropathic toxicities.
What is a drawback of protease inhibitors?
variable oral bioavailability, due to relatively poor absorption and extensive first-pass metabolism. (taken apart by digestive system)
What are some side effects of protease inhibitors? 5
- 1. diarrhea
- 2. nausea
- 3. paresthesias (tingling, pricking, numbness)
- 4. Indinavir- predisposes some individuals to nephrolithiasis (kidney stones) from precipitation of drug in kidneys
- 5. have been associated with development of diabetes
- mellitus and dyslipidemias(abnormal amt of lipids in
Nucleotide Inhibitors are a class of agents that have been in clinical trial for several years, but none is currently licensed.
Adefovir was the first nucleotide analog studied in clinical trials but was not approved by the FDA. Tenofovir is in clinical trials.
The optimal time to initiate HAART remains controversial.
After the protease inhibitors became widely available in 1996, with often dramatic decreases in morbidity and mortality, one early principle of treatment was to "treat early, treat hard."
A number of authorities believed that individuals infected with HIV should receive antiviral therapy
regardless of stage of disease and viral load.
Since 1998, there has been increasing concern regarding longer term complications of HAART which include (4)
- 1. lipodystrophy syndrome (redistribution of fat)
- 2. diabetes
- 3. dyslipidemias (abn amt of lipid in bld)
- 4. multi drug resistance
- recommendations have been to delay the initiation of HAART in many asymptomatic individuals
What are some potential benefits for early treatment in HIV? 4
- 1. easier control of viral replication and mutations
- 2. preservation of immune function
- 3. delayed progression to AIDS
- 4. possibly less risk of drug toxicity
What are some risk of early treatment to HIV? 4
- 1. development of drug resistance
- 2. unknown long-term drug toxicities
- 3. limited choices of future anti-retrovirals
- 4. reduced quality of life
HIV lipodystrophy can be looked at as a combination of what 3 components?
- 1. hyperglycemia/diabetes
- 2. fat redistribution
- 3. hyperlipidemia
A number of glucose abnormalities have been described in patients receiving combination ART, what are the 3 abnormalities?
- 1. hyperglycemia/diabetes
- 2. fat redistribution
- 3. hyperlipidemia
Hyperglycemia, new onset diabetes mellitus, diabetic ketoacidosis, and exacerbation of preexisting diabetes mellitus have been associated with protease inhibitors
These problems appear to be due to beta cell damage and resulting peripheral insulin resistance. ~3-17% of those on protease inhibitors have hyperglycemia
Fat redistribution syndrome (2 types) fat accumulation and peripheral wasting in arms and legs. Fat accumulation is subacute in onset in visceral and on the surface.
Typically, there is a centripetal obesity, "buffalo hump", breast enlargement, and facial wasting. These changes occure without hypercortisolism or exogenous corticosteroids.
Hyperlipidemia is another problem in persons receiving ART, elevations in triglycerides and cholesterol with or without fat redistribution or hyperglycemia.
Dyslipidemias are most strongly associated with protease inhibitors and typically occur early in tx, often <1 month.
There has been a number of case reports of premature myocardial infarction and stroke associated with elevated cholesterol levels in HIV-infected persons.
The preicse cardiac event rate is not clear. It appears that changing from a protease inhibitor to a nonprotease inhibiotr regimen improves lipids.
Lactic acidosis is an unusual complication of NRTIs, but carries a high fatality rate. What are some identified risk factors? 3
- 1. female gender
- 2. obesity
- 3. prolonged history of NRTIs
What causes lactic acidosis with use of NRTIs?
from mitochondirla toxicity, NRTIs inhibit mitochondrial DNA polymerase, interferes with Krebs cycle, causes accumulation of pyruvate and a shift in the equilibrium between pyruvate to lactate.
What are the clinical manifestations of mitochondrial toxicity? 4
- 1. fatigue
- 2. nausea and vomitting
- 3. abdominal pain
- 4. hepatomegaly
- tx is still under study
The goal of HAART is to increase the CD4 cell count and decrease the HIV RNA level. Patients have been classified as 3
- 1. complete responders
- 2. complete non-responders
- 3. discordant responders
- CD4 increased, viral load increased (bad)
- CD4 decreased, viral load decreased
Herpes is a class of viruses that include 5
- 1. Varicella zoster- chicken pox & shingles
- 2. Epstein-Barr- mononucleosis
- 3. Cytomegalovirus- CMV
- 4. Herpes I oral
- 5. Herpes II gential
What are some common characteristics about Herpes infection?
after intitial infection, virus lies dormant in the body, periodically resurfacing to cause new outbreaks.
What are 2 types of Herpes simplex virus and how are they spread?
Herpes I and II, may be sexually transmitted
Where is Herpes I infection typically located on the body?
above the waist, in the oral cavity and on lips, but also in the eyes or on the epidermis.
Where is Herpes I present in the body?
has a potential for sexual transmission, it is present in saliva, stool, and urine and can be transmitted easily by nonsexual contact.
What are s/sx of Herpes I?
vesicles resulting from type 1 infection in the oral cavity are commonly referred to as cold sores or canker sores and often affect children younger than 5 years.
What ____% of genital herpes is spread by oral contact?