AIDS Flashcards
Human immunodeficiency virus (HIV) belongs to the lentivirus group of the retrovirus family.
Human immunodeficiency virus (HIV) belongs to the lentivirus group of the retrovirus family.
HIV attacks and destroys the infection-fighting CD4 T-cells of the immune system.
HIV attacks and destroys the infection-fighting CD4 T-cells of the immune system.
Loss of CD4 T-cells makes it difficult for the immune system to fight infections, ultimately leading to the Acquired Immunodeficiency Syndrome (AIDS).
Loss of CD4 T-cells makes it difficult for the immune system to fight infections, ultimately leading to the Acquired Immunodeficiency Syndrome (AIDS).
Mode of transmission
HIV is transmitted from one person to another through specific body fluids—blood, semen, genital fluids, and breast milk. These happens through
1) Having unprotected sexual intercourse with an infected person
2) Sharing infected syringes and needles (e.g. between intravenous drug users)
3) Mother-to-child transmission (during pregnancy, at birth or through breast feeding.
4) Transfusion with contaminated blood and blood products
who should be tested for hiv
Intravenous drug users
Person who have unprotected sex with multiple partners
Man who have sex with man
Commercial sex workers
Persons treated for STDs
Recipients of multiple blood transfusion
Persons who have been sexually assaulted Pregnant women – in Singapore, it is mandatory for all pregnant women to be tested, which explains the zero transmission rate from mother-to-child since 2008.
Diagnosis - HIV infection
Serum antibody detection
- -- HIV enzyme Immunoassay Antibody tests (HIV EIA tests)
- -- Western Blot
HIV RNA detection/ quantification (Viral Load)
—– nucleic acid amplification (PCR)
Presentation: Different stages
A) Acute (Primary) HIV Infection
B) The Asymptomatic Stage
C) Persistent Generalised Lymphadenopathy
D) AIDS & Related Conditions
A) Acute (Primary) HIV Infection
A) Acute (Primary) HIV Infection
This occurs soon after contracting HIV, and is a flu-like illness with swollen lymph nodes, fever, malaise and rash lasting about 2 to 3 weeks
B) The Asymptomatic Stage
B) The Asymptomatic Stage
There are no signs or symptoms; this stage persists for many years
C) Persistent Generalised Lymphadenopathy
C) Persistent Generalised Lymphadenopathy
Persistent unexplained lymph node enlargement in the neck, underarms and groin for more than 3 months
D) AIDS & Related Conditions
AIDS = CD4 < 200/mm3 OR presence of AIDS defining disease
This is the advanced stage of the disease and the person succumbs to infections by unusual organisms that the uninfected person can resist
The organs involved include lung, eyes, gastrointestinal tract, nervous system and skin
Systemic symptoms like fevers, unexplained weight loss and diarrhoea are also common
Rare cancers (e.g. Lymphoma and Kaposi sarcoma) may be found
26 opportunistic infection
1) TB
2) pneumocystis
3) CMV –> HSV
4) Candidiasis
5) wasting syndrome (lost >10% of wt)
6) dementia complex
Primary Goals of Anti-retroviral Therapy
Reduce HIV-associated morbidity and mortality
Prolong the duration and quality of survival Restore and preserve immunologic function
Maximally and durably suppress plasma HIV viral load
Prevent HIV transmission
Strategies to Achieve Treatment Goals
Selection of Initial Combination Regimen
- —- ART regimens recommended by DHHS guidelines have comparable efficacy
- —- Consider dosing frequency and symmetry, pill burden, drug interactions, potential side effects and cost
- —– Tailored to each patient to enhance adherence and thus improve long-term treatment success
Pretreatment Drug-Resistance Testing
—- studies suggest that the presence of transmitted drug-resistant viruses (6-16% prevalence) may lead to suboptimal virologic responses
Improving Adherence —– Conditions that promote adherence should be maximized prior to and after initiation of ART
Surrogate Markers in HIV
CD4
Viral Load
Surrogate Markers in HIV – CD4
CD4 count of a healthy person ranges from 500 to 1,200 cells/mm3
Indicator of immune function in HIV-infected patients
strongest predictor of subsequent disease progression and survival
use to determine urgency for initiating antiretroviral therapy
assessed at baseline and EVERY 3 months after treatment initiation. In clinically stable patients with suppressed (UNDETECTABLE) viral load, CD4 count can be monitored every 3–12 months.
use to assess response to antiretroviral therapy
—– adequate CD4 response is defined as an increase in CD4 count in the range of 50–150 cells/mm3 during the first year of therapy then 50 to 100 cells/mm3 per year until a steady state level is reached
use to assess the need for initiating or discontinuing prophylaxis for opportunistic infections
———— eg prophylaxis for pneumocystis pneumonia and toxoplasmosis are started when CD4 cells are <200 cells/mm3
Surrogate Markers in HIV – Viral Load
Viral load (plasma HIV RNA) is the amount of virus in the plasma
It is the most important indicator of response to antiretroviral therapy and can be useful in predicting clinical progression
Viral load is measured BEFORE initiation of therapy and within 2 to 4 weeks (not later than 8 weeks) after treatment initiation or modification, thereafter, EVERY 4 to 8 weeks until viral load suppressed
In patients on stable regimen and suppressed viral load, monitoring can be done EVERY 3 to 4 months (even 6 months)
Effective regimen generally achieve viral suppression (ie undetectable HIV RNA level) by 8 to 24 weeks
Optimal viral suppression is generally defined as a viral load persistently below the level of detection (ie undetectable)
Virologic failure is defined as a viral load >200 copies/mL after 24 weeks of therapy initiation
When to start ART?
Antiretroviral therapy (ART) is recommended for all HIVinfected individuals, regardless of CD4 cell count, to REDUCE the morbidity and mortality associated with HIV infection.
ART is also recommended for HIV-infected individuals to PREVENT HIV transmission.
It is important to educate patients regarding the benefits and considerations regarding ART, and to address strategies to optimize adherence.
On a case-by-case basis, ART may be deferred because of clinical and/or psychosocial factors, but therapy should be initiated as soon as possible.
Benefits of earlier treatment
Maintenance of a higher CD4 count and prevention of potentially irreversible damage to the immune system
Decreased risk for HIV-associated complications that can sometimes occur at CD4 counts >350 cells/mm3, including tuberculosis, non-Hodgkin’s lymphoma, Kaposi’s sarcoma, peripheral neuropathy, and HIVassociated cognitive impairment
Decreased risk of non-opportunistic conditions, including cardiovascular disease, renal disease, liver disease, and non–AIDS-associated malignancies and infections
Decreased risk of HIV transmission to others, which will have positive public health implications
Limitations of earlier initiation
Development of treatment-related side effects and toxicities
Development of drug resistance because of incomplete viral suppression, resulting in loss of future treatment options
Transmission of drug-resistant virus in patients who do not maintain full virologic suppression
Less time for the patient to learn about HIV and its treatment and less time to prepare for the need for adherence
Increased total time on medication, with greater chance of treatment fatigue
Increased cost
Conditions with increased urgency to start ART
Pregnancy
AIDS-defining conditions, including HIV-associated dementia (HAD) and AIDS-associated malignancies
Acute opportunistic infections (OIs)
Lower CD4 counts (<200 cells/mm3)
HIV-associated nephropathy (HIVAN)
Acute/early infection
HIV/hepatitis B virus coinfection
HIV/hepatitis C virus coinfection
Haha H pal
Factors to Consider When Selecting an Initial Regimen
Regimen selection should be individualized and should be based on a number of factors, including:
Patient’s understanding of HIV
Adherence issues
Financial situation - cost
Convenience
----- pill burden
----- dosing
frequency
----- food and fluid
considerations
Comorbidities – ADR, Drug interactions
Genotypic drug resistance testing
Predictors of virologic success
After initiation of effective ART, viral load reduction to undetectable level usually occurs within the first 12 to 24 weeks of therapy
Predictors of virologic success include:
1) low baseline viremia (low viral load to start with),
2) high potency of the ARV regimen, (can suppress replication of virus)
3) tolerability of the regimen,
4) convenience of the regimen,
5) excellent adherence to the regimen.
ART armamentarium
1) Reverse transcription inhibitors (NRTI)
2) NNRTI
3) Integrase inhibitors
4) protease inhibitors
5) Fusion/entry inhibitors.
- PK enhancer (ritonavir , cobicistat)
Antiretroviral Regimens (ART) Recommended combinations for patients naïve to ART
2 NRTIs + 1 PI (Protease inhibitor) (boosted with ritonavir or cobicistat):
- tenofovir + emtricitabine* (2-in-1, Truvada®) + darunavir (boosted with ritonavir)
2 NRTIs + 1 INSTI (Integrase inhibitor):
- tenofovir + emtricitabine* + (raltegravir or dolutegravir or elvitegravir)
- abacavir + lamivudine* + dolutegravir (3-in-1, Triumeq®)
2 NRTIs + 1 Fusion inhibitor
- tenofovir + emtricitabine* + Maraviroc (CCR5antagonist)
Alternative
2 NRTIs + 1 NNRTI:
- tenofovir + emtricitabine* + efavirenz (3-in-1, Atripla®)
- Lamivudine can substitute for emtricitabine, vis versa
Note: Ritonavir and cobicistat – are CYP450 3A inhibitors, use to increase concentrations of various ARV.
