HAART Access and HIV Neurological Complications (Brazil)

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

[email protected]


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


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


TrendsHeterosexual transmission

– Man (69.2%) – 42.1%

– Woman – 94.9%

Education : 50.3% < 8 years– Illiterate – 3.7%


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


Why was these policies to reduction

in prices so important?

Brasília – the capital of Brazil


Expenditures (US$ Millions) with ARV and Average Number of Patients under treatment - Brazil (1997-2004)


Patients on HAART in Brazil


- National Aids Expenditures

0

50.000

100.000

150.000

200.000

250.000

300.000

350.000

400.000

2004 2005

US$ Million


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%


* 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


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


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


• What is the importance of all these efforts?

Iguaçú Falls


• 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


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


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


Impact of ARV Therapy Policy

Cost Savings - US$ 2.2 billion

US$ 1.23 billion in hospitals and treatment of OI


Neurological manifestations of HIV infection in Brazil

Rio de Janeiro


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


Progressive Multifocal Leukoencephalopathy– Brazil: Incidence < Europe / USA

• Italy – 3th neurological disturbance– Antinori et al. J Neurovirol, 2001


• 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?


J Berger, J Neurovirol, 2003

Incidence of PML - University of Miami


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


IPEC / FIOCRUZ

May 2004

June 2004

IRIS and the incidence of PMLCinque et al. J Neurovirol, 2001


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


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


Brazil – A Tropical country

Special considerations

AmazonianJaguar (Onça pintada)


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


Silva N et al. J Acquir Immune Defic Syndr Hum Retrovirol, 1999.


Leprosy – HIV + patients unfavorable leprosy outcome?– Inflammatory reaction type 1 - IRS

IPEC / FIOCRUZ


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


Thank you!

Grazie mille!

[email protected]

HAART Access and HIV Neurological Complications (Brazil)

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