THE 2003 WHO GUIDELINES FOR ARV USE: PERSPECTIVES FROM A USER

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THE 2003 WHO GUIDELINES FOR ARV USE PERSPECTIVES
FROM A USER

• JOHN IDOKO MD,
• UNIVERSITY OF JOS, NIGERIA

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NIGERIA

• POPULATION 130 Million
• INFANT MORTALITY 79/1000
• MATERNAL MORTALITY 80/1000
• TOTAL FERTILITY 6.4
• ADULT LITERACY 55.5
• DEBT BURDEN 28 Billion

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HIV/AIDS Figures- end of 2002
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Median National HIV Prevalence Increase 1992-
2001
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HIV Prevalence in States (2001)
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The HIV/AIDS Pyramid
60,564 Reported AIDS Cases ( 2001)
1.2 million Estimated Actual AIDS Cases
(2001 Estimate)
3.1 million (aged 15-49) 3.47 million (all
ages) with HIV Infection (2001 Estimate)
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Current national response

• Political Commitment now present at the highest
  level
• Establishment of new multisectoral structures
  (PCA, NACA, SACA, LACA)
• New Plan with greater ownership (HEAP)
• Broader funding base
• Democracy has brought on more partners
• Better understanding of the epidemic and what
  works

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Key interventions planned and currently
implemented

• Massive Awareness Raising Campaigns
• Enhancing institutional and community capacities
  to respond to epidemic
• Commencement of a large National Anti-Retroviral
  Therapy Programme
• Improving surveillance, monitoring and evaluation
• Redesign of supporting policies
• Commencement of VCCT, MTCT, Vaccine, HBC
  initiatives etc.

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Nigerian ART Program
The Federal government of Nigeria in February
2002 commenced a nationwide provision of HAART
using combination of generic forms of NVP, d4T
and 3TC at a reduced cost targeting 10,000
adults, and 5000 children.
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Objectives of the Nigerian ARV Programme

• To improve the quality of life of PLWAs through
  the provision of ART.
• To strengthen the capacity of institutions
  designated to provide comprehensive care for
  PLWAs.
• To improve the uptake of VCT in the country.
• Ensure an ARV programme based on the best
  scientific evidence.

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INCLUSION CRITERIA (adults)

•   Patient 15 yrs
• Patient confirmed HIV positive  
• Ability to sustain access to ART
•  Willingness to come for follow-up visits
• Symptomatic HIV/AIDS
• CD4 cell count of

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Features (1)

• 10,000 patients enrolled in 25 Federal tertiary
  institutions into the government program and
  another 5,000 in private capacity in private and
  Government health facilities (Total about
  15,000)
• Highly subsidized drugs at 8/month
• However, private patients are buying at
  prevailing commercial rate (100/month)
• Monitoring tests and support treatment cost about
  50-70 every 6 months

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Features (2)

• d4T/3TC/NVP 1st line combination
• AZT/ddI/IND 2nd line combination
• TDF/ddI/LPV/r 2nd line combination
• Efavirenz NVP substitute
• Paediatric treatment started in 8 PMTCT sites
• Monitoring of CD4 (all centres), viral load (4
  now, additional 4 centres soon),
• Resistance testing planned for 2 centres (NIMR,
  NIPRD)

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Results at 12 months

• 10,000 patients on treatment in 25 centres
• All centres tertiary institutions in 17 states
• General comments on patients progress
• Clinical improvement including wt gain
• Increase in median CD4 counts in patients in all
  centres
• Suppression of viral load to below levels of
  detection in 80 of patients (NIMR, Lagos)

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Results from the Jos Centre

• Jos centre serves 5 states in North Central Zone
  with population of 16 million people
• Commencement of Programme May 2002
• 1,698 patients on ARV, 700 patients sponsored by
  the Nigerian ART programme, rest paying as
  private (commercial rate)
• Seven clinicians, 8 counselors and 2
  nutritionists
• Laboratory support from APIN laboratory with
  capabilities for CD4 cell count (manual
  automated) and viral load recently available.

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Results from the Jos Centre

• 1,698 patients enrolled, 1/2 of patients enjoying
  national ART (8) and the rest paying at
  commercial rate (100)
• 450 patients followed up for 12 months
• 176 males and 274 females
• Age ranges from 15 to 57 (mean37.7yrs.)
• Major adverse Events (hepatotoxicity 3, steven
  Johnsons syndrome 1)
• Withdrawals (4)
• 2 clinical and immunological failures (ART
  experienced patients)

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Figure 1 Monthly weight changes in patients on
ARVs
f
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Figure 2 CD4 cell counts in patients
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Advantages of the Nigerian regimen (d4T/3TC/NVP)

• Affordable cost
• Acceptable pill burden
• Potent regimen
• Can be used by men and women including pregnant
  women
• Allows for preservation of other combinations

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Disadvantages of the Nigerian Regimen
(d4t/3TC/NVP)

• Contains NVP which is the major antiretroviral
  agent used for PMTCT
• Drug resistance and cross resistance
• Hepatotoxicity of NVP
• Not effective in HIV-2 and Group O
• Major drug-drug interaction with Rifampicin
  (Nigeria has high TB incidence)

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Goals after one year

• Scale up ART to all 36 states of the country and
  Federal Capital Territory (Abuja) from 10,000 to
  20-25,000
• Achieve highest level of success (80
  suppression to below detection and 95
  adherence)
• Prevent resistance by optimizing treatment
  options
• Carry out evaluation to ensure success in all the
  above goals

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Major considerations in provision of ART in
Nigeria

• Access to limited number of drug combination
• Poor health infrastructure
• Need to deliver drugs to rural areas of the
  country where 65 of people live
• High incidence of Tuberculosis
• High incidence of HBV and (HCV)
• HIV subtypes (CFR02) and sub-sub types HIV-1 A3

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Table 1 Age and sex related prevalence of HIV,
HBV and HCV in HIV infected population on ART in
Jos, Nigeria
Idoko et al 2003
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Considerations in ART scaling up in Resource
limited countries

• Current tension is between the desire for
  immediate large scale access to ART vs
• Provision of durable drug combinations with long
  term benefit and hence sustainable public health
  good
• Balance between immediately available drugs
  against the development of durable agents
• Therapeutic principle should therefore be if it
  doesnt work, better not to treat!

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Durability and Scalability

• The goal should NOT be lets get the drugs there
  and see despite enormous pressures to scale up
  in resource limited countries
• We need therapeutic options that will last
• Without proper evaluation, therapeutic problems
  (resistance) may crop up in 2-3 years
• Hence before scaling up, there is need for
• Information on effectiveness of regimens,
  patterns of resistance and co-morbidities (TB,
  HBV, HCV)
• Monitoring and Evaluation
• Validation of the programme

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Urgent questions for the Nigeria ART program
before scaling up

• What of patients achieve months on d4T/3TC/NVP?
• What mutations are present in patients failing on
  the current regime?
• What mutations in patients with
• Any polymorphisms?

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WHO Guidelines Questions that remain?

• Are there ways to prioritize/individualize WHO
  guidelines on the criteria for starting ART?
• Is there an appropriate CD4 count to initiate
  treatment of an asymptomatic HIV individual?
• We need to explore the roles of various adherence
  strategies such as DOT, pill boxes, buddy systems
  on ART.

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WHO Guidelines Questions that remain?

• Further research is needed to understand
  resistance with single dose NVP especially as it
  impacts on outcomes of HAART programmes
• We need further research to see if clinical
  monitoring is really sufficient for effective
  patient management of patients on ART.

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Recommendations

• We need to build capacity (human resources
  infrastructure)
• We need to monitor programmes (commodity, MIS and
  drug security)
• We need to monitor patients on ART to define
  clinical and immunological progress (CD4 counts)
  and have some reference laboratory monitor viral
  load
• There is need for further reduction in the costs
  of ARVs (especially Brands), Tests Kits for
  Diagnoses Treatment Monitoring as well as the
  Treatment of OIs.

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Recommendations -

• We need to carry out Program Evaluation at the
  national level to ensure durability of treatment
  combinations
• Resistance sentinel surveillance at national or
  regional level should be a vital component to
  track resistance profiles of available
  antiretroviral drugs
• Collaboration at local and international
  Partnerships

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CONCLUSION

• As we work towards 3/5, we need to ensure
• treatment strategies that will be durable
• demonstrate success from the beginning
• We must learn lessons from the use of NVP in
  PMTCT and more than a decade of experience using
  antiretroviral therapy

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Thank You