The Challenge of HAART in the Caribbean Eyes Wide Shut or Eyes Wide Open

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The Challenge of HAART in the Caribbean Eyes
Wide Shut or Eyes Wide Open

• Bernard Liautaud, Moïse Desvarieux, Roland
  Landman, André Cabié, Sylvie Abel et Pierre Marie
  Girard

 Intrepide  Group  Centre Hospitalier
Universitaire de Fort de France Division of
Epidemiology, School of Public Health,University
of Minnesota Institut de Médecine et
dÉpidémiologie Africaine, Hôpital Bichat/Claude
Bernard, Paris Service de Maladies Infectieuses
et Tropicales, Hôpital St Antoine, Paris
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Once-a-day HAART in treatment-naïve HIV-infected
adults in Senegal

• Feasibility of antiretroviral evaluation in
  Senegal
• Long term efficacy with high rate of virological
  and immunological responses in a population of
  patients with advanced immune deficiency and high
  viral load at baseline.
• High compliance as assessed by PK study and
  patient questionnaire and virological success

Roland Landman et al, AIDS, 17, 1017-1022, 2003
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The gap between access and need
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Declaration of President Nelson Mandela
We have failed to translate our scientific focus
into action where it is most needed in the
communities of the developing world, the poorIts
our belief that the single most imporant step we
must now take is to provide access to treatment
throughout the developing world. There is no
excuse for delay !!!!
Opening ceremony, IAS, 2nd Conference on AIDS,
July 13-16 , 2003 Paris, France
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30.000 deaths/year people in need of HAART
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ART in the Caribbean Bahamas

• Prevalence 3,5, urbanized p. 89
• 2002 350 HIV under bi-therapy Only mother
  and children and costs 3600/pt/year
• 2003 1200/6000 HIV under triple therapy Cost
  of Triple therapy 200/pt/year, provided free
  of charge

Perry Gomez, a success story, 2002 Laurie
Garet, Newdays.com, 2004
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ART in the Caribbean Bahamas
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ART in the Caribbean Barbados

• Prevalence 1,2
• 106 new cases (57,1 B or C) in 2002
• Reinforcement Aids program 2001
• Financing World Bank
• Modern ambulatory care unit Ladymead Reference
  Unit (LRU)
• Comprehensive care (including ART, Counselling,
  Adherence)

N. Adomakoh, SA Adomakoh et al TC Roach et al
IAS, 2nd Conference on AIDS, July 13-16 , 2003
Paris, France
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ART in the Caribbean Barbados

• ART started in 2002
• April 2003 236 beneficiaries
• Included for evaluation 83
• Median cell CD 4 183/µl (52lt200)
• AZT/3TC/EFV 60,5
• AZT/3TC/IDV 12,8

N. Adomakoh, SA Adomakoh et al TC Roach et al
IAS, 2nd Conference on AIDS, July 13-16 , 2003
Paris, France
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ART in the Caribbean Barbados

• Adherence rate gt95 at 28 week 85
• 69 viral load ND at 4-6months
• Median cell CD4 100 cell/ml

N. Adomakoh, SA Adomakoh et al TC Roach et al
IAS, 2nd Conference on AIDS, July 13-16 , 2003
Paris, France
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ART in the Caribbean Barbados
Results 2002 vs 2001 43 Aids related
mortality 59 number of hospital
admissions/year 40,8 hospitalization
cost/pt 29,9 hospital days 27,8
days Outpatient visits 128
N. Adomakoh, SA Adomakoh et al TC Roach et al
IAS, 2nd Conference on AIDS, July 13-16 , 2003
Paris, France
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GHESKIO Research-based Model
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THE PROBLEM

• Estimated Haitian Population 8.500.000
  inhabitants
• 652 health facilities with the 1/3 in capital
  periphery.
• HIV national prevalence 4.5 (2000)
• ( rural 2.91 urban 6.74)
• 300.000 PLWHIV 160.000 AIDS orphans
• GHESKIO unique urban VCT with free services for
  STI/AIDS

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The GHESKIO VCT urban model with integrated
services
STI Management
Post-HIV exposure Counseling and HAART
Pre-test Counseling HIV, Syphilis, Tuberculosis
Post-Test Counseling
Same day TB screening / Rx / Px
Reproduction Health Services (family planning and
prenatal care) HIV women Prevention HIV MTCT
with HAART

• Care to HIV infected individual/ affected family
• OI Rx/Px
• HAART to HIV positive women in MTCT with
• CD4 count ? 200
• Nutritional support
• Psychosocial support

Rx Treatment Px Prophylaxis
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GHESKIOs population for HAART (2002)

• Already requiring treatment 600
• New persons coming for HIV testing 3000/year
• New population requiring HAART 1017
• Total adult population requiring HAART 1617
  patients

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The MSPP/GHESKIO extension project to small
cities

• Develop with Ministry of Health 27 VCT centers
  throughout the country (15 from public / 12 from
  private sector), 10 being centers of excellence
• Association public sector / private sector.
• Availability of integrated services
  STI/HIV/TB/FP
• Direct beneficiaries 250.000 persons

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Interaction of VCT in health facilities
GHESKIO / MSPP
Groupe III
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Groupe I
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Groupe II
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(Zami la sante)
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NIPPES
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Zami la Sante  Rural Model Project
Boucan Carré Clinic, before extension of DOT-HAART
Boucan Carré Clinic, after extension
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DOT-HAART Model Zami la Sante Directly
observed therapy for HIV/AIDS

• 450 patients under HAART with everyday
  follow-up
• One accompagnateur attached to every patient
• The accompagnateur (commonly a community health
  promotor) observe all drug take
• Triage of patients priority to who were most
  seriously ill

Paul Farmer et al, 2nd Conference on AIDS, 10th
Conf on Retroviruses d Opportunistic Infections,
Febr 2003
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DOT-HAART Model Zami la Sante Directly
observed therapy for HIV/AIDS

• 2 year mortality rates (100 patients, 1999-2003)

Paul Farmer brought immense hope among the rural
patients with no access to ARV treatment
Paul Farmer et al, 2nd Conference on AIDS, 10th
Conf on Retroviruses d Opportunistic Infections,
Febr 2003
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CISIH
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Comprehensive Health Care Management
MARTINIQUE/French Hospital-based Model
AIDS hot line 24/24hrs
The Patient
Domestic chores and home help
Regular in-patient hospitalisation
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EVOLUTION DES STRATÉGIES THÉRAPEUTIQUESCISIH
Martinique
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SURVIVAL RATES AFTER AIDSCISIH Martinique
Before 1996 (n 254) 24 months Survival
0.452 Since 1996 (n 161) 24 months Survival
0.734 LOGRANK p lt 0.0001
SINCE 1996
Before 1996
(months)
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Why HAART in the Caribbean? Ethical principles
of justice and equity

• But how will justice be respected on launching
  HAART programs urban vs rural population on
  which criteria should patients be selected for
  treatment, lottery or positive discrimination
• HIV pregnant women ?
• patients participating in research ?
• patients eating at least 2 times a day ?
• patients living not too far from medical sites ?
• Patients prone to adherence ?
• What clinical/lab criteria should be use to
  qualify patients for HAART if lacking basic
  health care facilities?

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Why HAART in the Caribbean Ethical principles
of justice

• But allocating resources, do justice should
  refer only to HIV? What about malnutrition,
  diarrheal diseases, mother and child mortality,
  vaccinations programs... ?
• Should not each country/territory participate in
  protecting its own future (Incoming generations)
  as well as other peoples future against
  developpement of HIV resistant variants to ARV ?

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Resistance to ARV in developed Countries (1995-199
8 compared to 1999-2000 S. Little et al)

• frequency of high-level resistance to one or more
  drugs increased from 3.4 to 12.4

• frequency of multidrug resistance increased from
  1.1 to 6.2
• frequency of resistance mutations detected by
  sequence analysis increased from 8.0 to 22.7

S. Little, S. Holte, JP Routy et al. N Engl J
Med, Vol. 347, No. 6 August 8, 2002
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Resistance to ARV in France (1996-2000, Chaix et
al, AIDS, 17, 2635-2643, 2003)

• genotypic drug resistance mutations in primary
  HIV infections stable around 10
• (vs British cohort with resistance mutations
  detected in 27 in 2000)
• increase of non B subtypes from 10.6 to 19

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Resistance to ARV in developing Countries

• Ivory Cost 57 of resistance to at least one
  drug among 68 patients with prior exposure to ARV
  (Adje C. Et al, 2001)
• 19 to gt40 of resistance mutations associated
  to Nevirapine 6-8 weeks after exposure to single
  dose of Nevirapine for MTCT prevention (Eshleman
  S. et al, 2001 Martinson et al, 2004)

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Resistance to ARV in the Caribbean

• In Martinique primary resistance documented (gt
  10) and transmission of up to 8 drug-resistant
  viruses observed (G. Dos Santos) 1.5 to 2 of
  patients in therapeutic deadlock
• Barbados experiencing first virological failures
  on 2nd and 3rd line therapy (16 drugs available)

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Robert Gallo director of the U.S.-based Institute
of Human Virology

• Obviously it is critical to get available drugs
  to developing nations as quickly as possible, but
  not just to throw this at them," Gallo,, told
  Reuters. ...the danger of failure is very real in
  a few years if the drugs are just dumped there,"
• "We've got to have infrastructure created at the
  same time because we are going to create
  multi-drug resistant mutants if we don't."
  "Nobody talks about that...the danger of failure
  is very real in a few years if the drugs are just
  dumped there,"
• "There'll be great happiness with the drugs being
  made available, as I would see the future, for
  two to five years and then we're going to start
  seeing problems if it is not done right."
  (Reuters, 2003)

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Bill Blattner Institute of Human Virology,
University of Maryland
The epidemic of drug resistance may rob mankind
of its best hope and create an even greater
tragedy
CREDHAC meeting, Ponce, Puerto-Rico, Feb 29-30,
2004
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How Much Adherence is enough? Correlation
Between Adherence and Virologic Failure
(n) patients with virologic failure
gt95 90-95 80-90 70-80 lt70
Adherence ()
D Paterson et al. 6th Conference on Retroviruses
and OIs, Chicago, February 1999 Abstract 092.
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Why HAART in the Caribbean? Increasing of Local
and International funding Global Funds WHO 3x5
Target, Pres. Bush initiative

• But 95 price reduction is still too high for
  majority of patients, and reduction do not
  include other costs lab tests for follow-up,
  medication for OI, nutrition supplementation....

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Why HAART in the Caribbean? Increasing of funding

• But How Health care authorities will manage the
  discrepancy between the budet dedicated to
  HIV/STI programs and others aimed at other public
  health priority programs emerging problems with
  disparity of salaries between Aids and non-AIDS
  health care workers in Haiti (VCT workshop,
  P-au-P, Nov 5-7 and Nouvelliste, Nov 11, 2003)
• which proportion of STI/HIV budget will stay
  attributed to prevention programs and to
  treatment and care?

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Why HAART in the Caribbean? Increasing of funding

• But Promoting VCT must benefit patients how
  long can we be waiting between promoting HIV
  screening in all sites and availability of HAART?
  
• Improving lab facilities for diagnosis and
  follow-up of ARTshould be balanced with
  investments necessary in basic laboratories
  (hematology, biochemistry, immunology) they are
  necessary for detection of side effects of HAART
  as well as for improving general care to all
  patients with or without AIDS

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Determinants of therapy outcomeDiscontinuation
of HAART in naive patients (n862)
Toxicity 58.3
Failure 14.1
Non-adherence 19.6
Italian Cohort
Other 8.0
I
C
O
N
A
Naive Antiretroviral
Monforte et al. AIDS 200014499-507
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- ARV prescription must be limited to care
centers possessing the necessary technical means
(drug logistics, trained staff, laboratory
facilities...).
Dakar 2000 recommendations
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- ARV Treatment and follow-up Minimum .Blood
cell count .Transaminase .Serum
creatinine .Urinary strip . CD4 cell
count
Dakar 2000 recommendations
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Why HAART in the Caribbean? Increasing of funding

• But Necessity to take into account the lack of
  electrical power in some country and related
  expenses
• Refrigeration is required not only for lab
  reagents but also for storage of some ARV
  (Ritonavir, Lopinavir/r) which should not be
  prohibited in developing countries, since they
  appear to be a key power-related factor in
  prevention of drug resistance

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Why HAART in the Caribbean? Centers of Excellence

• Among the best research and care centers in the
  Americas in the field of STI/HIV prevention
  programs and care of opportunistic infections
  (Gheskio Centers, Zanmi la Sante in Haïti)
• Same for Puerto Rico, the French territories
  (DFA), Barbados, Bahamas, Trinidad and Tobago,
  Cuba, Dominican Republic, Jamaica
• They can exchange experiences and provide Help to
  other countries

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Why HAART in the Caribbean? Centers of Excellence

• But limited application of research outputs on
  the general population (for ex TB prevention)
• Human resources too scare regarding the national
  challenge lack or training programs to cope with
  this public health disaster
• Clinics already overwhelmed with number of
  patients and lack of space to deliver acceptable
  quality of care to patients

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HAART in the Caribbean some conditions for succes

• Access to HAART is ethically mandatory and should
  be free of charge
• No way Caribbean peoples should be deprived of
  ARV because developed countries fear the increase
  of HIV variants resistant to ARV
• Imperious necessity to set up a national team
  with the highest technical expertise

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HAART in the Caribbean some conditions for succes

• 4. Strategies for preserving the future (1) a
  common ethical issue for all neighbouring
  countries
• appropriate management of ARV strong procurement
  storage plans for continuous availability of
  medications (first and second line is a minimum)
• design of locally adapted guidelines for
  efficient ARV regimens

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HAART in the Caribbean some conditions for succes

• 4. Strategies for preserving the future (2)
• Specific plans for adherence a condition for
  funding ART programs
• Monitoring of drug resistance at the population
  level (sequential samplings)

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HAART in the Caribbean some conditions for succes

• 5. Implementation of HAART can and must be done
  in a phased approach first in limited pilot sites
  with qualified human ressources, then expanded
  ASAP today it is still a technical and complex
  issue
• 6. A switch from individual and hospital-based
  approach to public mass therapy program
  clinical/community based approach may fit some
  places

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HAART in the Caribbean some conditions for succes

• 7. Implementation must be carefully monitored
  through reliable reports of outcomes and ensure
  that a policy for drug disappearance is not
  substituted to a policy of treatment
• 8. Take steps now to launch infrastructures and
  training programs necessary to extend HAART
  through the National VCT programs and open access
  to all persons in need as quickly as possible.
  Improve now access to palliative care and OI
  treatment (reduction of costs)

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HAART in the Caribbean some conditions for succes

• 9. Special programs promoting confidentiality
  and compassion to every PLHIV and fighting
  stigmatisation clearly informing population that
  ARV access do not resolve the HIV epidemic
• Sustainability of national programs should depend
  on economical growth of the country and
  comprehensive development of health care
  facilities.
• In 1989, L. Manigat one Haitian Candidate to the
  Presidency promised to every haitian access to
  one full meal a day....How will we manage to
  promote 95 compliance to ARV regimen?

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Non! Fok je nou toujou byin Kalé
?
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EYES WIDE SHUTby Stanley Kubrick
Alice (Nicole Kidman) to Bill Hartford (Tom
Cruise) The Important thing is were awake
now, and hopefully for a long time to
come Limportant est que nous soyons maintenant
réveillés, et espérons le pour très longtemps