Antiretroviral therapy

1
Antiretroviral therapy
Dr SUMI THOMAS MD, DVD, DNB ART MEDICAL
OFFICERCALICUT MEDICAL COLLEGE
2
What is HAART?
3
Highly Active Antiretroviral Therapy (HAART)

• Combination of different classes of
  antiretrovirals
• to achieve maximal and most durable suppression
  of viral replication
• prevent emergence of drug resistant mutants
• to improve survival quality of life

4
Progression to AIDS/Death
No therapy
Mono-therapy
Dual-therapy
of patients progressing
Triple therapy
Months
JAMA 1998 CMAJ 1999
5
Goals of HAART

• Clinical goals Prolongation of life
  improvement in quality of life.
• Virologic goals Greatest possible reduction in
  viral load for as long as possible to halt
  disease progression and to prevent or delay
  resistance.
• Immunologic goals Immune reconstitution that is
  both quantitative (CD4 within normal range) and
  qualitative (pathogen specific immune response)

6
Goals of HAART

• Therapeutic goals Rational sequencing of drugs
  in a fashion that achieves clinical, virologic,
  and immunologic goals while
• a) Maintaining therapeutic options
• b) Minimizing drug toxicities side effects and
  
• c) Maximizing adherence
• Epidemiological goals Reduce HIV transmission

7
Indications for ART - HIV-infected patient

• (regardless of viral load)
• WHO Stage IV Treat irrespective of CD4 count
• WHO Stage I, II, III Guided by CD4 count.

8
Program recommendations

• Adults and adolescents satisfying any of the
  following criteria can be offered therapy

9
What steps should be followed before starting
therapy?
10
Clinical History

• HIV specific symptoms-present past
• Past history jaundice, TB, Coronary artery
  disease, Dyslipidaemia Others
• Personal history smoking, alcohol drugs
• Family history diabetes, hypertension etc.
• Sensitive sexual history Genital ulcers, other
  STIs, high risk behaviours etc.
• Treatment history ARVs, contraceptives in women,
  herbal drugs, etc.

11
Physical Examination

• Weight, Height, BMI
• Oral cavity, Lymph nodes, Skin, eyes
• Genital examination
• Vital signs
• Systemic examination- all systems
• Ophthalmic Fundus examination.
• Quality of life assessment

12
Baseline evaluation

• Confirm HIV results
• Symptom/sign driven tests to rule out OIs
• Complete Blood counts
• CD4 test
• LFT, Creatinine, HBsAg, Chest x-ray, VDRL/TPHA,
  PAP Smear
• Optional tests Lipid profile, Pregnancy test,
  HCV test etc.

13
Before Initiating Therapy...

• Treatment Preparedness Counseling
• Assess readiness for treatment adherence

14
What to start ?
15
Currently available antiretrovirals
Entry inhibitor Enfuviritide (T-20)
16
Highly Active Antiretroviral Therapy (HAART)

• ZIDOVUDINE NEVIRAPINE
• OR LAMIVUDINE
  OR
• STAVUDINE EFAVIRENZ

17
How should a patient on ART be followed up?
18
Monitoring ARV Therapy Effectiveness of regimen

• Clinical signs/symptoms
• Weight gain
• Resolution of oral thrush
• Resolution or reduced frequency of other
  infections
• CD4 count
• Viral load reduction (not included in the
  national program)

19
Monitoring ARV therapy Adverse effects and
toxicity of regimen

• Clinical signs/symptoms
• Rash
• Jaundice
• Abdominal pain
• Numbness or pain in extremities
• Laboratory abnormalities

20
Serious adverse effects of NRTIs

• Lactic acidosis/fatty liver
• All NRTIs
• Anemia
• zidovudine

• Pancreatitis
• Stavudine
• Lamivudine (in children)
• Neuropathy
• stavudine

Potentially life-threatening
21
Pigmentation of the Nails (Due to AZT)
22
Nevirapine Rash (1)
23
Nevirapine Rash (3)
24
Nevirapine Rash (4)
25
NVP Hepatitis with rash
Acknowledgement Dr.Ramesh, ART Medical officer,
Namakkal GH.
26
Emerging Toxicities of HAART

• Lipodystrophy
• Dyslipidemia
• Insulin Resistance
• Lactic Acidosis
• Osteopenia and avascular necrosis

27

• Examples Acute toxicities.

28

• Examples Chronic toxicities.

29
HAART - Promises

• Potent suppression of viral replication (? HIV
  RNA)
• Immune reconstitution (? CD4)
• ? risk of progression of disease
• Improved quality of life
• Improved survival

30
HAART - Problems

• Not a cure
• Pill burden
• Drug toxicity
• Drug interactions
• Need for strict adherence

31
Successful HIV therapy requires rigorous adherence

• gt95 adherence is necessary to achieve viral load
  lt400 copies/ml in 81 of patients1
• A 10 reduction in adherence associated with a
  doubling of HIV RNA level2
• 80 adherence may be sufficient to achieve
  therapeutic goals in other chronic disease states
  (e.g., hypertension)3

1. Paterson D et al. Ann Intern Med.
200013321-30 2. Bangsberg DR et al. AIDS.
200014357-366 3. Luscher TF et al. J
Hypertens. 19853(suppl 1)S3-S9
32
Long-term Efficacy of ART No Magic Bullet, No
miracle
Adherence Adherence Adherence
Adherence Adherence Adherence
Adherence Adherence Adherence
Adherence Adherence Adherence

Adherence Adherence Adherence