haart access and hiv neurological complications (brazil)
TRANSCRIPT
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
HAART Access and Neurological Complication of HIV Infection:Impact versus Resources in Brazil.
Marcus Tulius T Silva, MD, MSc.
Neurologist – The Reference Center for Neuroinfections and HTLV
Evandro Chagas Clinical Research Institute
Oswaldo Cruz Foundation (FIOCRUZ)
Rio de Janeiro – Brazil
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Brazil in numbers
Federative Republic
Population (2005) - 183.592.493
Life Expectancy (2001) – 68.7 years
Economic Rank (2004) -15th
GDP U$ 482 billion
Per capita GDP US$ 2,699
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
AIDS in Brazil
Accumulated AIDS cases (1984-2004): 362.364
•Incidence rate (2004): 18.4/100.000
Patients > 14 years old: 348.578 (96.2%)
Patients under HAART (2005) – 155.000
• 20.000 patients/year
Estimated number of people living with HIV (2005): 600.000
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
TrendsHeterosexual transmission
– Man (69.2%) – 42.1%
– Woman – 94.9%
Education : 50.3% < 8 years– Illiterate – 3.7%
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
ARV Access Program - Major aspects
Universal and free of charge access to ARV’s since 1991
Protease inhibitors - 1996
Local policies
Political commitment
Local generic drug production
Negotiation for high discount
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Why was these policies to reduction
in prices so important?
Brasília – the capital of Brazil
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Expenditures (US$ Millions) with ARV and Average Number of Patients under treatment - Brazil (1997-2004)
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Patients on HAART in Brazil
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
- National Aids Expenditures
0
50.000
100.000
150.000
200.000
250.000
300.000
350.000
400.000
2004 2005
US$ Million
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Access to treatment3 imported drugs take up 63% of the budget - 2003
LPV.r NFV EFZ 12 other ARVs
Exp
end
itu
res
(in
mill
ion
s o
f R
$)
121
131
106
215
2003
21%
23%
19%
573
37%
LPV.r+ EFZ+ NFV
63%
12 other ARVs
37%
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
* generic version available – local production
- patented medicines
ZIDOVUDINE (ZDV)* DIDANOSINE (ddI)*LAMIVUDINE (3TC)* STAVUDINE (d4T)* ABACAVIR INDINAVIR* TENOFOVIR
RITONAVIR* SAQUINAVIR NELFINAVIR AMPRENAVIR NEVIRAPINE* EFAVIRENZ LOPINAVIR / r ATAZANAVIR
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
ARV Access Program - Major aspects
National networks
– HIV viral load - 66 labs
– CD4+ cell count - 78 labs
– Genotypic - 12 labs
– ARV Logistic control system - 480 dispensary units
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
HIV/AIDS units
Qualified hospitals: 375
Day hospitals: 79
Home care assistance: 54
Outpatient services: 381
Source: UDAT/PN-DST-AIDS. March/2002
2
11
1122
1
1
2
21
531
1
11
5 31 1
4 32
1
2 1193 1 4
11
221
3111
1113
2 1 1 1
4 4
633 133210 5
5015186158174924
11 1 7 114 410
321 9 9
1
6 1 8
Access to Treatment in Brazil - 889 units for treatment
Laboratories: Viral Load, CD4+ count and Genotyping
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
• What is the importance of all these efforts?
Iguaçú Falls
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
• 1995 - 22.509 AIDS cases, 15.134 deaths (9.7:100000)
• 2002 - 32.526 AIDS cases, 11.276 deaths (6.4:100000)
84 95 2002
Year of death
pe
r 1
00
,00
0 i
nh
ab
.
men
women
Brazil
Number of Deaths - 1995 vs 2002
16
14
12
10
8
4
2
0
Source: Brazilian STD/AIDS Program
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Source: Chequer et al, 1992; Marins et al. 2002
58
18
50
10203040506070
1989 1995 1996
Mo
nth
s o
f su
rviv
al
Median survival after AIDS Diagnosis in Brazil
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Impact of the Brazilian ARV Policy
Reduction of mortality 40%
90,000 prevented deaths
Reduction of morbidity 70%
Reduction of hospitalizations 80%
Average hospitalizations / patient per year
• 1,65 in 1996
• 0,28 in 2003
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Impact of ARV Therapy Policy
Cost Savings - US$ 2.2 billion
US$ 1.23 billion in hospitals and treatment of OI
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Neurological manifestations of HIV infection in Brazil
Rio de Janeiro
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Pathology of the CNS in Brazil - 252 autopsy cases
– CNS lesion in 230 cases (91.3%)• Toxoplasmosis 34.1%
• Cryptococcosis 13.5%
• CMV infection 7.9%
• HIV encephalitis 6.7%
• PLCNS 4%
Chimelli L et al. Neuropathol Appl Neurobiol 1992;18(5):478-88
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Progressive Multifocal Leukoencephalopathy– Brazil: Incidence < Europe / USA
• Italy – 3th neurological disturbance– Antinori et al. J Neurovirol, 2001
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
• JCV Seroprevalence in Brazil – 92% (Padgett e Walker)
• Low incidence also in Africa and IndiaShankar SK et al. J Neurovirol,
2003
•Difficulty in diagnostic?
•Difference in JCV isolates?
•Difference in interactions between JCV and local HIV strains?
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
J Berger, J Neurovirol, 2003
Incidence of PML - University of Miami
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
LMP in Brazil– Federal University of Rio de Janeiro
(Chimelli, personal communication)
• 1998 to 2005 – 10 cases
– IPEC – FIOCRUZ• 1985 to 1995 – 1 case
• 1996 to 2005 – 10 cases
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
IPEC / FIOCRUZ
May 2004
June 2004
IRIS and the incidence of PMLCinque et al. J Neurovirol, 2001
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
HIV-Dementia– Developed country – 40 to 50% reduction
• Incidence rate 3% per year (7% before HAART)
– Brazil – lack of official statistics• IPEC – FIOCRUZ
– 35 cases (6.5% neurological cases) before 1996
– 19 cases (3.1% neurological cases) after 1996
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Peripheral neuropathy (PN)– Most common neurological complication
– ↑ prevalence
PN in Brazil - São Paulo – Prevalence of 69.4%
– 64.7% subclinical
» Zanetti et al. Arq Neuropsiquiatr, 2004
• IPEC – FIOCRUZ – clinical PN 13.3% (81 out 605) after 1996
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Brazil – A Tropical country
Special considerations
AmazonianJaguar (Onça pintada)
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Reduviid bugs
Chagas Disease – Trypanosoma cruzi Chronic CD – reactivation
• Febrile syndrome
• Meningoecephalitis +/- miocarditis– Reactivation in HIV + patients
» CNS involvement 75%
» Rare CNS involvement in HIV negative patients
T. Cruzi in a cardiac muscle fiber.Helene Santos Barbosa / IOC / Fiocruz
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Silva N et al. J Acquir Immune Defic Syndr Hum Retrovirol, 1999.
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Leprosy – HIV + patients unfavorable leprosy outcome?– Inflammatory reaction type 1 - IRS
IPEC / FIOCRUZ
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
In summary Benefits of HAART
• Brazil = Developed countries– Universal access HAART
– Strict adherence to guidelines
Urgent needs• National network to surveillance about the incidence
and the prevalence of neurological complications in HIV infection
Ministry of HealthOswaldo Cruz FoundationEvandro Chagas Clinical Research Institute
Thank you!
Grazie mille!