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Antiretroviral Treatment of Adult with HIV Infection The guidelines of International Antiviral Society - USA Panel
1. Antiretroviral Treatment of Adult with HIV
Infection
The guidelines of International Antiviral
Society - USA Panel
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
IM-Infectious Diseases Division
March 2014
2. Brain storm
Which statement about initiating Anti Retroviral therapy (ART) according to (WHO)
and International Antiviral Society - USA Panel recommendation is most TRUE?
A. Treat if CD4 count is <200.
B. consider treatment if CD4 count is <350 and initiate ART before CD4 count falls
below 200.
C. Treat irrespective of CD4 count.
D. Do not treat till CD4 count is < 100.
E-Treat if CD4 count is < 500 .
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
3. Which statement about initiating drug therapy (ART) according to (WHO) and International
Antiviral Society - USA Panel recommendation is TRUE?
A. Treat if CD4 count is <200.
B. consider treatment if CD4 count is <350 and initiate ART before CD4 count falls below 200.
C. Treat irrespective of CD4 count.
D. Do not treat till CD4 count is < 100.
E-Treat if CD4 count is < 500 .
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
4. 40 years old male , diagnosed 3 years ago with HIV , he was doing well with CD4
count 725 copies/ml at the time of diagnoses , he missed follow up with HIV
Specialist , now he came with feeling of fatigue and generally unwell , CD4 count
is 455 copies/ml , Viral load is 11800 copies /ml , other investigations all are
normal , you decided to start ART after disused and agreed by patient , what will
be the initial regimen of ART ?
A-Darunavir plus abacavir/lamivudine
B-Lopinavir/r plus tenofovir
C- tenofovir/emtricitabine
D-Efavirenz/tenofovir/emtricitabine
E- Efavirenz plus Darunavir/r.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
5. A-Darunavir/r plus abacavir/lamivudine
B-Lopinavir/r plus tenofovir
C- tenofovir/emtricitabine
D-Efavirenz/tenofovir/emtricitabine (AIa) .
E- Efavirenz plus Darunavir/r.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
6. Classify the following Antiretroviral Agent by its action: efavirenz
A.Nucleoside reverse transcriptase inhibitors
B.Non-nucleoside reverse transcriptase inhibitors
C.Protease Inhibitors
D- Integrase Inhibitor
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
7. Classify the following Antiretroviral Agent by its action: efavirenz
A.Nucleoside analog reverse transcriptase inhibitors
B.Non-nucleoside reverse transcriptase inhibitors
C.Protease Inhibitors
D- Integrase Inhibitor
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
8. Recommendation and Rationale
MAIN RECOMMENDATION
The New recommendations for HIV patient care include offering ART to all patients regardless of
CD4 cell count .
Rationale
Patients starting ART when CD4 counts are < 350/μL have greater morbidity and mortality than
those starting when CD4 counts are < 500/μL
Increasing evidence of detrimental effects of uncontrolled viremia at CD4 cell counts > 500/µL
Uncontrolled HIV replication, immune activation and inflammation associated with increase risk
of ‘non-AIDS’ illnesses like Cardiovascular, hepatic, renal diseases and malignancies and ART
with high CD4 associated with decreased incidence of diseases .
Thompson et al, JAMA, 2012
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
9. In the HIV-CAUSAL collaboration Study , there was a significant and steady
decrease in AIDS-free survival as the CD4 cell count threshold for initiation of
therapy decreased .
There was an estimated 38% increase in the hazard of AIDS or death when therapy
was initiated below a CD4 cell count of 350/µL compared with 500/µl.
The COHERE study of 75 336 individuals examined the prognostic value of the CD4
cell count after virologic suppression by ART and noted that higher CD4 cell count
was associated with incremental decreases in the risk of new AIDS events, all-
cause mortality, and non AIDS mortality .
Thompson MA, Aberg JA. Antiretroviral Treatment of Adult HIV Infection 2012 Recommendations of the International Antiviral Society–USA Panel. The Journal of American
Medical Assocation. 2012.;308(4) .
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
10.
11.
12.
13. What is the Benefits from Early Start
ART .
Prevention of progressive immune dysfunction (reduced immune activation)
Delayed progression to AIDS and prolonged survival
Decreased risk of non-AIDS/HIV-related morbidity (HIVAN, malignancies, neurocognitive
dysfunction, cardiovascular disease, etc)
Decreased drug resistance
Decreased risk for some ARV toxicities
Decreased HIV transmission
Thompson et al, JAMA, 2012
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
14. What is the Risk from Early Start ART
Reduced quality of life
Development of drug resistance if adherence is suboptimal
Limitation in future choices of ART if drug resistance occurs
Uncertain long-term toxicities and duration of effectiveness for some drugs/regimens
Possible transmitted drug resistance
Thompson et al, JAMA, 2012
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
15. Strength and quality of evidence are highest
with
CD4 count < 500 cells/µL
Pregnancy
HBV or HCV co infection
HIV-associated nephropathy
Active or high risk for cardiovascular disease
Opportunistic infections, including tuberculosis and meningitis
Age older than 60 years
Primary HIV infection
High risk for HIV transmission
Thompson et al, JAMA, 2012.
16. CD4 < 500 cells/µL (AIa)
CD4 > 500 cells/µL (BIII)
Pregnancy (AIa)
Chronic HBV (AIIa)
HCV (may delay until after HCV treatment if CD4 > 500) (CIII)
Age older than 60 (BIIa)
HIV-associated nephropathy (AIIa)
Acute phase of primary HIV infection, regardless of symptoms (BIII).
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
17. Summary of New WHO
Recommendations June 2013
As a priority, ART should be initiated in all individuals with severe or advanced HIV clinical
disease (WHO clinical stage 3 or 4) and individuals with CD4 count ≤350 cells/mm3 .
ART should be initiated in all individuals with HIV with CD4 count >350 cells/mmsup>3 and ≤
500 cells/mmsup>3 regardless of WHO clinical stage .
ART should be initiated in all individuals with HIV regardless of WHO clinical stage or CD4 cell
count in the following situations:
1- Individuals with HIV and active TB disease .
2- Individuals coinfected with HIV and HBV with evidence of severe chronic liver disease .
3- Partners with HIV in serodiscordant couples should be offered ART to reduce HIV transmission
to uninfected partners .
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
18. All pregnant and breastfeeding women with HIV should initiate triple ARVs (ART), which
should be maintained at least for the duration of mother-to-child transmission risk.
First-line ART
should consist of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a non-nucleoside
reverse-transcriptase inhibitor (NNRTI).
TDF + 3TC (or FTC) + EFV as a fixed-dose combination is recommended as the preferred
option to initiate ART .
If TDF + 3TC (or FTC) + EFV is contraindicated or not available, one of the following options is
recommended:
1-AZT + 3TC + EFV
2- AZT + 3TC + NVP
3- TDF + 3TC (or FTC)
Consolidated ARV guidelines, June 2013.
WHO, HIV/AIDS.2013http://www.who.int/hiv/pub/guidelines/arv2013/intro/rag/en/index4.html.
19.
20.
21. Baseline assessment
Evaluate for HBV or HCV coinfection, diabetes mellitus, hyperlipidemia, cardiovascular disease,
smoking, renal disease, other comorbid conditions
Consider drug interactions
Perform resistance testing
Assess for pregnancy
Patient readiness for treatment should be considered when deciding to initiate ART.
Thompson et al, JAMA, 2012.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
22. Important considerations
ART is recommended and should be offered to persons during the acute phase
of primary HIV infection, regardless of symptoms (BIII)
ART should be started as soon as possible, preferably within the first 2 weeks
of diagnosis, in patients with opportunistic infections (AIa)
The optimal timing for patients with cryptococcal meningitis is less certain,
but initiating ART early during cryptococcal treatment may be associated with
higher mortality; therefore, ART initiation in these patients should be
managed in consultation with experts (BIII)
Thompson et al, JAMA, 2012
23.
24.
25. ART is recommended in all HlV-infected persons with tuberculosis (TB) and should
be started within 2 weeks of TB treatment when the CD4 cell count is below 50/µL
and by 8 to 12 weeks for those with higher CD4 cell counts (Ala).
The optimal timing for patients with TB meningitis is less certain, but ART should
be started within the first 2 to 8 weeks of diagnosis and managed in consultation
with experts (BIII).
Thompson et al, JAMA, 2012.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
32. The Initial Regimen
Tenofovir/emtricitabine (TDF/FTC) OR Abacavir/lamivudine (ABC/3TC)
With third agent (NNRTI, boosted PI, or InSTI):
Efavirenz OR
Atazanavir/r OR
Darunavir/r OR
Raltegravir
Thompson et al, JAMA, 2012.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
33. 2NRTIs + NNRTIs
Efavirenz/tenofovir/emtricitabine (AIa)
Efavirenz plus abacavir/lamivudine (AIa) in HLA-B*5701-negative patients with
baseline plasma HIV-1 RNA <100,000 copies/Ml.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
34. 2 NRTIs + PIs
Darunavir/r plus tenofovir/emtricitabine (AIa)
Atazanavir/r plus tenofovir/emtricitabine (AIa)
Atazanavir/r plus abacavir/lamivudine (AIa) in patients with plasma HIV-1
RNA <100,000 copies/mL
2 NRTIs + Integrase Inhibitor
Raltegravir plus tenofovir/emtricitabine (AIa) .
35. Alternative to Initial Antiretroviral
Regimens
NNRTI plus nRTIs
Nevirapine plus tenofovir/emtricitabine or abacavir/lamivudine (BIa)
Rilpivirine/tenofovir/emtricitabine (or rilpivirine plus abacavir/lamivudine) with
baseline plasma HIV-1 RNA < 100,000 copies/mL (BIa)
PI/r plus nRTIs
Darunavir/r plus abacavir/lamivudine (BIII)
Lopinavir/r plus tenofovir (BIa) (or abacavir/lamivudine) (BIa)
InSTI plus nRTIs
Raltegravir plus abacavir/lamivudine (BIIa)
Elvitegravir/cobicistat/tenofovir/emtricitabine** (BIb)
Thompson et al, JAMA, 2012
36.
37. Important Notes
Efavirenz
once daily dose .
must be taken on an empty stomach, preferably at bedtime ( increased
efavirenz concentrations observed following administration with food may
lead to an increase in frequency of adverse reactions ) .
Dosing at bedtime may improve the tolerability of nervous system symptoms
Psychiatric symptoms, including insomnia, nightmares, confusion, memory
loss, and depression, are common , and more serious symptoms such as
psychosis may occur in patients with compromised liver or kidney function.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
38. Women of childbearing potential should undergo pregnancy testing before
initiation of efavirenz (EFV) and receive counseling about the potential risk to the
fetus and desirability of avoiding pregnancy while on EFV-based regimens(AIII).
Because the risk of neural tube defects is restricted to the first 5 to 6 weeks of
pregnancy and pregnancy is rarely recognized after 4 to 6 weeks of pregnancy
Federally approved HIV/AIDS medical practice guidelines. Aids Information. http://aidsinfo.nih.gov/drugs/269/efavirenz/0/professional.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
39. Especial Considerations
Severe hepatotoxicity and rash with nevirapine are more common in initial
therapy when CD4 cell count is >250/µL in women and >400/µL in men.
Tropism assay to confirm R5 virus should be done before prescribing maraviroc.
Maraviroc is not effective in persons who have X4 or dual/mixed X4/R5 virus
infection. Few data are available for maraviroc with tenofovir/emtricitabine or
abacavir/lamivudine
In patients with or at high risk of cardiovascular disease, avoiding use of abacavir,
lopinavir/r, or fosamprenavir/r might be considered (BIIa)
Thompson et al, JAMA, 2012.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
40. In patients with reduced renal function, tenofovir should be avoided, or if
treatment for HBV coinfection is needed, dosing should be adjusted according
to the prescribing information (AIIa)
Given the increased risk of fragility fractures, it may be prudent to avoid
tenofovir as part of initial therapy in postmenopausal women (BIIa)
The recommended initial ART regimen in the setting of rifampin based
tuberculosis treatment is efavirenz plus 2 nRTls (AIa)
Thompson et al, JAMA, 2012.
41. The recent recommendation for use of a 3-month, once-weekly regimen of isoniazid with
rifapentine for treatment of latent TB infection is not recommended for HlV-infected patients
receiving ART (BIII).
The ART regimen for HIV- and HBV coinfected persons should include tenofovir and
emtricitabine or lamivudine as the nRTI background (AIIa)
Thompson et al, JAMA, 2012.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
42. Patient Monitoring
Plasma HIV-1 RNA levels should be monitored at least every 3 months after
treatment is initiated or changed for virologic failure to confirm suppression
of viremia below 50 copies/mL (AIa).
CD4 cell count should be monitored at least every 3 months after initiation of
therapy, especially among patients with less than 200/µL, to determine the
need for primary opportunistic infection prophylaxis (BIII).
Once viral load is suppressed for 1 year and CD4 cell count is stable at 350/µL
or greater, HIV-1 RNA and CD4 cell count can be monitored at intervals of up
to 6 months in patients with dependable adherence (CIII).
Thompson et al, JAMA, 2012.
43. Detectable HIV-1 RNA (>50 copies/mL) during therapy should be confirmed in a
subsequent sample between 2 and 4 weeks afterward and prior to making
management decisions (BIII)
Sustained elevation of HIV-1 RNA between 50 and 200 copies/mL should prompt
evaluation of factors leading to failure and consideration of switching of ART (BIII)
Baseline genotypic testing for resistance should be performed in all treatment-
naive patients (AIIa) and in cases of confirmed virologic failure (AIa)
Thompson et al, JAMA, 2012.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
44. Therapeutic drug monitoring is not recommended in routine care; however,
selected patients (eg, pregnant women, children, and patients with renal or liver
impairment) might benefit from this intervention (BIII)
Health care practitioners and health systems should initiate strategies to monitor
and improve entry into and retention in care and ART adherence and to
incorporate and analyze quality-of-care indicators (CIII)
Thompson et al, JAMA, 2012.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
45. Conclusions
Recommendation to begin therapy earlier in asymptomatic persons is informed by
Increased evidence of the harmful effects of uncontrolled viremia and its
associated immune activation and inflammation, even at higher CD4 cell counts
Evidence that all HIV-infected adults may benefit from ART
Data showing ART reduces likelihood of transmission of HIV.
ART is recommended and should be offered regardless of CD4 cell count(BIII).
ART is recommended and should be offered to persons during the acute phase of
primary HIV infection, regardless of symptoms (BIII).
Thompson et al, JAMA, 2012.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
46. ART should be started as soon as possible, preferably within the first 2 weeks of
diagnosis, in patients with opportunistic infections (other than cryptococcal and
tuberculous meningitis),with attention to drug interactions and the potential for
immune reconstitution inflammatory syndrome (IRIS) (AIa).
The optimal timing of ART initiation in patients with cryptococcal meningitis is less
certain, but initiating ART early during cryptococcal treatment may be associated
with higher mortality; therefore, ART initiation in patients with cryptococcal
meningitis should be managed in consultation with experts (BIII).
Thompson et al, JAMA, 2012.
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
47. ART is recommended in all HlV-infected persons with TB and should be started
within weeks of TB treatment when CD4 cell count is below 50/µL and by 8 to
12 weeks for those with higher CD4 cell counts (AIa).The optimal timing for
patients with TB meningitis is less certain, but ART should be started within
the first 2 to 8 weeks of TB treatment and managed in consultation with
experts (BIII).
Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH
48. Presented by : Dr Hythum Salah Hassan –MBBS-AAHIVS.
KAMC--NGHA-RIYADH