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HIV

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Amanda Gaspelin

on 28 April 2015

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Transcript of HIV

HIV
Cultures of sexual adventurism as markers of HIV seroconversion: a case control study in a cohort of Sydney gay men
Among homosexual men, which factors predict the likelihood of contracting HIV?
Previous studies found to be inconsistent
Certain factors significant in some studies while not in others
Structure of study places importance on context of participants as opposed to singular characteristics
Introduction
Methods
Results
Need to better educate men in target areas while also avoiding stigmatization
Involving gay businesses may be effective
Counseling highly important for men in serodiscordant relationships
Discussion/Limitations
Medication:
pre-exposure prophylaxis (PrEP)
Taken as a daily pill
Tenofovir, taken by men and transgender women who sleep with men, led to a 44% reduction in HIV incidence.
The same drug, taken by heterosexual men and woman, had an efficacy of 62.2%
post-exposure prophylaxis (PEP)
Taken immediately after potential exposure to HIV
Shown by the Journal of Infectious Disease to be “feasible for persons at risk for HIV infection” as no participants developed HIV antibodies during the 6 month study.

Risk Management for Sexual Transmission
Drug users should:
If possible, stop drug use
Use only sterile injection equipment and water
Never share needles or syringes
Clean the injection site
Take a pre-exposure prophylaxis (PrEP) medication
Drug users experience a 48-49% reduction in HIV incidence while taking the PrEP tenofovir disoproxil fumarate

Risk Management for Drug Users
Behavior:
Consistent use of condoms
Consistent testing with partner
Modification of Sexual Behavior
Male circumcision
Shown to decrease the risk of HIV infection in heterosexual males by 60%

Risk Management for Sexual Transmission cont.
Expecting mothers with HIV/AIDS should:
Take antiretroviral therapy (ART) during pregnancy, labor, and delivery
Have a C-section
Avoid Breastfeeding
Have their child tested and treated

If the father has HIV/AIDS while the mother is HIV negative, the father should continue treatment, and the mother should take precautions mentioned on the previous slide, with a constant regimen of pre-exposure prophylaxis

Risk Management for children of HIV/AIDS infected parents
HIV is spread through bodily fluids, excluding sweat, saliva, and tears.
Groups at the greatest risk are:
Drug users who share needles
Men who have sex with men
Those who have sex with multiple partners
Individuals who already have sexually transmitted diseases
Young People
Other Groups at risk include:
Children of mothers with HIV/AIDS
Health Care workers

Risk Factors for HIV
Sources
Short Term:
Anemia
Diarrhea
Dizziness
Fatigue
Headaches
Nausea and vomiting
Pain and nerve problems
Rash

Side Effects of Treatment
Five “classes” of HIV/AIDS drugs
Entry Inhibitors
 interfere with the virus' ability to bind to receptors on the outer surface of the cell it tries to enter. When receptor binding fails, HIV cannot infect the cell.
Fusion Inhibitors
 interfere with the virus’s ability to fuse with a cellular membrane, preventing HIV from entering a cell.
Reverse Transcriptase Inhibitors
 prevent the HIV enzyme reverse transcriptase (RT) from converting single-stranded HIV RNA into double-stranded HIV DNA-a process called reverse transcription. There are two types of RT inhibitors.
Integrase Inhibitor
s
 block the HIV enzyme integrase, which the virus uses to integrate its genetic material into the DNA of the cell it has infected.
Protease Inhibitors
 interfere with the HIV enzyme called protease, which normally cuts long chains of HIV proteins into smaller individual proteins. When protease does not work properly, new virus particles cannot be assembled.

Classes of Antiretrovirals
HIV/AIDS care requires a
REGIMEN
.

Treatments cannot be neglected even temporarily, or the risk of increased viral load and drug resistance development rise.

HIV/AIDS Treatment cont.
There is no cure for HIV/AIDS; its secondary prevention consists of slowing the spread of the disease, and improving the quality of life of the patients.
Current HIV/AIDS medications seeks to improve symptoms, control the amount of virus in the body, and protect the patient’s immune system
Individually, the drugs are antiretrovirals (ARVs). Taken as a set (“3 different antiretroviral drugs from 2 different classes,” as recommended by aids.gov) they are Highly Active Antiretroviral Therapy (HAART/ART)
A collection of drugs like this is sometimes referred to as a “cocktail,” though the traditional AIDS cocktail has been replaced by the more effective ARVs

HIV/AIDS Treatment
“The risk of health care workers being exposed to HIV on the job (occupational exposure) is very low, especially if they use protective practices and personal protective equipment to prevent HIV and other blood-borne infections. ”-cdc.gov

Transmission from a needle used on an infected HIV patient is less than 1%

Still, precautions concerning the proper handling and disposal of needles, as well as protective gloves and gear, should be followed to ensure safety.

Risk Management for health care workers
Prevention and Treatment
Cdc.gov/hiv
“Sexual Risk Factors for HIV Infection in Early and Advanced HIV Epidemics in Sub-Saharan Africa: Systematic Overview of 68 Epidemiological Studies”
“Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomized, double-blind, placebo-controlled phase 3 trial”
“Feasibility of Post exposure Prophylaxis (PEP) against Human Immunodeficiency Virus Infection after Sexual or Injection Drug Use Exposure: The San Francisco PEP Study”
“Antiretroviral Pre-exposure Prophylaxis for Heterosexual HIV Transmission in Botswana”
http://www.who.int/hiv/topics/malecircumcision/en/
https://www.aids.gov/hiv-aids-basics/just-diagnosed-with-hiv-aids/treatment-options/overview-of-hiv-treatments/index.html
http://www.cdc.gov/hiv/basics/prevention.html
http://www.cdc.gov/hiv/risk/gender/pregnantwomen/facts/index.html
http://www.cdc.gov/hiv/basics/transmission
http://www.niaid.nih.gov/topics/HIVAIDS/Understanding/Treatment/pages/arvdrugclasses
http://www.cdc.gov/hiv/prevention/research/prep/
http://www.aidsmeds.com/articles/1667_24192.shtml
https://www.aids.gov/hiv-aids-basics/just-diagnosed-with-hiv-aids/treatment-options/side-effects/index.html
http://www.theaidsinstitute.org/education/aids-101/where-did-hiv-come-0
http://kff.org/global-health-policy/fact-sheet/the-global-hivaids-epidemic/
http://biotech.law.lsu.edu/Books/lbb/x590.htm
http://library.med.utah.edu/WebPath/TUTORIAL/AIDS/HIV.html
http://genomebiology.com/2013/14/1/201
http://www.aids.org/topics/aids-faqs/how-is-hiv-transmitted/
http://kff.org/global-health-policy/fact-sheet/the-global-hivaids-epidemic/

Jemmott, John B., PhD, Loretta S. Jemmott, PhD, RN, FAAN, and Geoffrey T. Fong, PhD. "Abstinence and Safer Sex HIV Risk-Reduction Interventions for African American Adolescents." The Journal of the American Medical Association. JAMA Network. Web. 29 Mar. 2015

Sterne, Jonathan, Hernan, Miguel, Ledergerber, Bruno. “Long term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study.” The Lancet. (2005). Print. 2 April 2015.

Long Term:
Lipodystrophy
–A problem in the way your body produces, uses, and stores fat. (Also called “fat redistribution”). These changes can include losing fat in the face and extremities, and gaining fat in the abdomen and back of the neck.
Insulin Resistance
–A condition that can lead to abnormalities in your blood sugar levels and, possibly, diabetes.
Lipid abnormalities
–Increases in cholesterol or triglycerides.
Decrease in bone density
–Can be a significant issue, especially for older adults with HIV. This can lead to an increase risk of injury and fractures.
Lactic acidosis
–A buildup of lactate, a cellular waste product, in the body. This can cause problems ranging from muscle aches to liver failure.


Sample
Procedure
Analysis
S.KIPPAX, D.CAMPBELL, P.VANDEVEN, J.CRAWFORD, G.PRESTAGE, S.KNOX, A.CULPIN, J.KALDOR & P.KINDER
Members of Sydney Men and Sexual Health cohort study (1100 homosexually active men living within one hour of Sydney)
Control group: non seroconverters (HIV -)
Seroconverters compared to those who remained HIV (-) throughout study
Study began with 369 controls, confirmed HIV (-)



History
HIV Life Cycle
Controversial naming
“GRID”
1982
“AIDS”
1983
Studying of the virus begins
Virus’s first name
HTLV-III/LAV (human T-cell lymphotropic virus-type III/lymphadenopathy-associated virus) by an international scientific committee.
The name was later changed to HIV
1999
Origins were reported

History cont.
Retrovirus
(RNA)
Reverse Transcriptase
RNA/DNA
HIV genetic information into the host’s genome
Host Cells
WBC
T lymphocytes
Helper T cells
CD4+ T cells
Rapid T cell death post HIV infection post budding
Slow decline of helper T cells in the body

Mechanism
General Overview
Distributions
Through
Blood (including menstrual blood)
Semen
Vaginal secretions
Breast milk

Not through
Saliva
Tears
Sweat
Feces
Urine

Transmission
Acute infection symptoms
Fever
Swollen glands
Sore throat
Rash
Fatigue
Body aches
Headache

Signs and Symptoms
Acute Infection
Clinical Latency
AIDS

Stages
Introduction
Progress of participants throughout trial

Methods cont.
Participants= 659 African American adolescents (mean age, 11.8 years)
6th-7th grade classes of 3 middle schools serving low-income communities in Philadelphia
53% female, 26.8% lived with both parents
Pre-intervention questionnaire-
25.2% reported ever having sexual intercourse
15.4% reported having sexual intercourse in the previous 3 months
1.6% reported having same-gender sexual relationships


Methods
Offered $100, $40 at the end of 2-session intervention, and $20 for each follow up
Adolescents were stratified by gender and age
Randomly assigned to 1 of 3 interventions
Abstinence HIV intervention
Safer-sex HIV intervention
Health promotion intervention (control group)
8 1-hour modules divided over 2 consecutive Saturdays

Methods cont.
Interventions based on social cognitive theory, theory of reasoned action, its extension, and theory of planned behavior
Adult facilitators were 25 African American adults (mean age, 39.5 years)
Peer facilitators were 45 Philadelphia high school students (mean age, 15.6 years)
Participants completed questionnaires before and after intervention, and at 3-,6-, and 12-month follow-ups.


Methods cont.
African American adolescents at high risk of contracting HIV
Behavioral interventions can reduce HIV risk-associated sexual behavior
Not known which interventions/facilitators are most effective
Achieved through abstinence or safer-sex strategy

Background
Limitations
Culture sensitive interventions can reduce HIV risk-associated sexual behavior of young inner-city African American adolescents
Safer-sex interventions curbed unprotected sexual intercourse
Safer-sex interventions may have longer-lasting effects than abstinence interventions

Discussion
Less sexual intercourse and less unprotected sexual intercourse observed after safer-sex intervention
Adolescents in both HIV-prevention groups scored higher in HIV risk-reduction knowledge
Abstinence was effective in short-term, but its effects diminished
Sex education does not increase sexual activity


Results cont.
Participants who had peer facilitators liked their intervention more
No significant difference in risk-related behavior reduction
Those in abstinence group were less likely to have sexual intercourse in 3- month follow up than those in the control group (OR, 0.45)
Those in safer sex group were more likely to report consistent condom use at 3-month follow up than those in the control group (OR, 3.38) or abstinence group (OR, 3.10)

Results
Questionnaires asked about sexual behavior, demographic variables, and mediator variables
Primary outcomes- sexual behavior in previous 3 months
Secondary outcome- potential mediators of the effect on intervention


Methods cont.
Abstinence and Safer Sex HIV Risk-Reduction Interventions for African American Adolescents
A Randomized Controlled Trial
John B. Jemmott III, PhD; Loretta Sweet Jemmott, PhD, RN, FAAN; Geoffrey T. Fong, PhD

Swiss HIV Cohort Study
Excluded
Deaths before 1996
Refused treatment
Were on HAART at baseline
Clinical Stage C at baseline
Uncertain History
Observational Prospective Cohort Study

Methodology: Study Design: Observational Cohort Study
Previous clinical trials
CD4/Viral Loads
Reductions in disease progression
1 Year or less

No HAART placebo trials
Ethics
Long term effectiveness


Background cont.
Monthly Intervals
CD4, HIV RNA, haemoglobin
None, Dual, or HAART
CDC Stage B Event

Methodology: Statistical Analysis
HAART vs No Treatment
2161 patients
HAART vs Dual Therapy
1276 patients

400 (12%)AIDS/Death total
13,652 patient years; 53% on HAART


Results
HAART
Highly Active Antiretroviral Therapy
1 protease inhibitor,
2 reverse transcriptase inhibitors

Background
Limitations
HAART slows progression to HIV/AIDS
Consistent with RCT’s comparing HAART to dual therapy
Time and Significance
Lower Effectiveness in IDU


Discussion
Rate Reduction
86% reduced rate of AIDS/Death compared to no treatment
51% compared to dual treatment
Stronger association with weighted Cox model
Eliminates confounders
HAART more beneficial with more time

Results: Cox Models
1276 patients
196 (15%) ->AIDS/Death
Rate Ratio: .8 (95% CI)



Results: HAART vs. Dual Therapy
2161 patients
202 on HAART->AIDS/Death
54 events on HAART vs 148
Rate Ratio: .79 (95%)

Results: HAART vs No Treatment
Long Term Effectiveness of Potent Antiretroviral Therapy in Preventing AIDS and Death: A Prospective Cohort Study
Staging similar with similar CD4/Viral counts
Assumed once on therapy-> stayed on therapy
AIDS and Death
IDU
Adherance

Infectious Dz
HIV
Human Immunodeficiency Virus
Subtypes
HIV 1
HIV 2
Structure
Mechanism

Where did HIV come from?

Chimpanzee in West Africa
SIV
1959
First HIV-1 case
1970’s
Appearance in the U.S
1979-1981
Increase of PNA, CA and other illnesses reported by doctors in L.A and N.Y among Male PT who had relations with other men
Correlation of decrease in immune system health

AIDS symptoms
Weight Loss
Fever/ Night Sweats
Extreme lethargy
Lymphadenopathy
Chronic diarrhea
Sores of the mouth, anus, or genitals
PNA
Neurologic disorders
Kaposi’s Lesions

Primary outcome was measure with self-reports and might be inaccurate
May not be generalizable to all young inner-city African American adolescents
Unclear if effects would be observed in other populations, such as, older African American adolescents or suburban white adolescents

Jonathan Sterne, Miguel Hernan, Bruno Ledergerber, Kate Tiling,
Rainer Weber, Pedram Sendi, Martin Rickenbach, James Robins, Matthias Egger
Weighted Cox models
Hazard Ratios
Purpose of Weight
Control time dependent confounders
CD4 count
Follow ends when
AIDS
Death

Groups
HAART
Dual
No Treatment

Progression slower for HAART
Rate Ratio .7 (95% CI)
Higher rates
Low baselines CD4
High baseline RNA
Age
IDU
CDC Stage B events

Sarah Rodriguez
Amanda Gaspelin
Corina Lopez
Tiernan Middleton
Maggie Porter
Thank You!
Need confirmation from other cities
Highly limited in sample size and location
Responder bias
Men were periodically interviewed and given a structured questionnaire based on their lifestyle
1 hour completion time
Interview date occurred less than 1 to 13 months before first HIV (+) test
Data taken from most recent interview prior to seroconversion (1993-1995)
Questionnaire based on the following variable families:
Demographic
Contextual
HIV knowledge
Sexual practice & drug/alcohol use
Preferences & attitudes
* All questions regarding sexual practices refer to the 6 months prior to taking the questionnaire
Demographic
Contextual
HIV Knowledge
Sexual practice & drug/alcohol use
Preferences & Attitudes
Age the only demographic marker for seroconversion
Seroconverters significantly younger
Cases- 29
Controls- 34
Self identification as gay/homosexual had no significant correlation
23 of the original 369 had seroconverted by 1995
8 in 1993
8 in 1994
7 in 1995
Study ran 1993-1997
Having a known (+) partner significantly distinguishes seroconverters
Other markers for seroconversion include:
living in the inner city
higher general sexual involvement
However it was not the number of partners that distinguished, but WHERE the partners were sought...
Nature of sexual relationships (ie casual vs monogamous) showed no significant difference
Nor did involvement in the gay community
Accuracy of HIV knowledge was not indicative of seroconverters vs controls
However seroconverters were more likely to believe in withdrawal as a safe option
General drug use during sexual encounters distinguished seroconverters
Particularly amylnitrite ("amyl" or "poppers")
Alcohol use did NOT distinguish cases from controls despite the high correlation between drug and alcohol use
Seroconverters prioritized anal intercourse
Participation in "esoteric" sexual practices (fisting, sex toys, group sex etc.) highly significant
Very few men reported participating in/enjoying these practices
But of those few, seroconverters made up the most
Frequency of these practices in controls almost nonexistent
No significant difference in attitude towards condom use
However seroconverters more likely to have had unprotected sex in a casual encounter
Full transcript