Opportunistic Infections in HIV-infected Patients An Overview

Wanla Kulwichit, MD Infectious Diseases Chulalongkorn University

SEARCH Regional HIV/AIDS Training 8th January to 9th February, 2007

Supported by A Training Grant From

TB & HIV

MDR-TB more than non-HIV? Same Rx or longer? Rifampin V.S. antiretrovirals When to start antiretrovirals? Beware of immune recovery!

Primary MDR-TB: HIV - nonHIV

Primary MDR-TB: HIV - nonHIV

Int J Tuberc Lung Dis 2000; 4: 537-43

Primary MDR higher among HIV (8.5%) than nonHIV (4.4%) P = 0.022
Int J Tuberc Lung Dis 2001; 5: 32-9

Same or longer?

N Engl J Med 1995; 332: 779-84

Optimal duration of treatment is uncertain

CDC NIH IDSA Statement MMWR December 17, 2004

Optimal duration of therapy for HIV-1related TB disease remains controversial

CDC NIH IDSA Statement MMWR December 17, 2004

Prolonged therapy recommended for patients with delayed CLINICAL or BACTERIOLOGIC response
CDC NIH IDSA Statement MMWR December 17, 2004

SYMPTOMATIC or POSITIVE CULTURE at or after 2 months of therapy

CDC NIH IDSA Statement MMWR December 17, 2004

Rifampicin and HAART: problems with PI and NNRTI

Rifam-nevirapine: CONTRAINDICATED!

MMWR 1998; 47 (RR-20)

Nevirapine and rifampin

Data are insufficient to assess whether dose adjustments are necessary
MMWR 2000; 49: 185-9

Nevirapine and rifampin (contd) Rifampin and nevirapine should be used only if clearly indicated and with careful monitoring
MMWR 2000; 49: 185-9

Co-administration of rifampin and nevirapine in HIV-infected patients with tuberculosis

AIDS 2003,

17:637642

-36 pts, 4 lost to follow-up -all pts cured of TB -74% undetectable viral loads -median CD4 increase 116/cu.mm.
AIDS 2003,
17:637642

Nevirapine high therapeutic index

With dose of 400 mg/day, steady state Cmin 4.5 + 1.9 microgram/ml IC50 for the drug = 0.00250.025 microgram/ml J Infect Dis 1995, 171:537545

What do experts say?

Annu Rev Med 2004; 55: 283-301

Updated Guidelines for the Use of Rifamycins for the Treatment of Tuberculosis Among HIV-Infected Patients Taking Protease Inhibitors or Nonnucleoside Reverse Transcriptase Inhibitors

http://www.cdc.gov/nchstp/tb/tb_hiv_drugs/toc.htm

Updated Guidelines for the Use of Rifamycins for the Treatment of Tuberculosis Among HIV-Infected Patients Taking Protease Inhibitors or Nonnucleoside Reverse Transcriptase Inhibitors

http://www.cdc.gov/nchstp/tb/tb_hiv_drugs/toc.htm

Updated Guidelines for the Use of Rifamycins for the Treatment of Tuberculosis Among HIV-Infected Patients Taking Protease Inhibitors or Nonnucleoside Reverse Transcriptase Inhibitors

http://www.cdc.gov/nchstp/tb/tb_hiv_drugs/toc.htm

What do experts say? (contd)

THE LANCET Vol 363 April 17, 2004

What does a pseudoexpert need to say?

THE LANCET Vol 364 July 24, 2004

What does a pseudoexpert need to say? (contd)

THE LANCET Vol 364 July 24, 2004

What does the expert counter-say? (contd)

THE LANCET Vol 364 July 24, 2004

Immune Reconstitution Inflammatory Syndrome (IRIS)

Immune reconstitution syndrome Immune restitution syndrome Immune recovery syndrome Paradoxical response

Case 1: pretreatment

Am J Roentgenol 2000; 174: 43-9

Case 1: improved, posttreatment

Am J Roentgenol 2000; 174: 43-9

Case 1: worsening, postHAART

Am J Roentgenol 2000; 174: 43-9

Case 2: pretreatment

Am J Roentgenol 2000; 174: 43-9

Case 2: worsening postHAART

Am J Roentgenol 2000; 174: 43-9

Case 2: finally improved

Am J Roentgenol 2000; 174: 43-9

Case 3: pretreatment

Am J Roentgenol 2000; 174: 43-9

Case 3: worsening postHAART

Am J Roentgenol 2000; 174: 43-9

Paradoxical worsening of TB postHAART: PPD conversion

Am J Resp Crit Care Med 1998; 158: 157-61

Incidence of IRIS: HIVnonHIV; HAART-nonHAART

Am J Resp Crit Care Med 1998; 158: 157-61

IRIS: any pretreatment clinical clue?

Am J Resp Crit Care Med 1998; 158: 157-61

More extrapulm diseases and lower CD4 in IRIS

Chest 2001; 120: 193-7

Delayed HAART until after 2 months of TB treatment, regardless of CD4 count

Am J Respir Crit Care Med 2001; 164: 7-12 BMJ 2002; 324: 802-3

Starting HAART early: CD4 < 100 Delay HAART (2mths): CD4 > 100
AIDS 2002; 16: 75-83

When to start ART?

Waiting for controlled studies (until then) decision should be individualized
CDC NIH IDSA Statement MMWR December 17, 2004

When to start ART? (contd)

Avoid simultaneous prescription most HCPs wait at least 4-8 weeks
CDC NIH IDSA Statement MMWR December 17, 2004

Algorithm: focal brain lesions

American Academy of Neurology 1997

Algorithm: focal brain lesions

American Academy of Neurology 1997

Algorithm: Toxoplasmic encephalitis

Montoya& Remington 2000

Mycobacterium avium complex

Infections at low CD4 count (likely < 50 ; very likely < 75) No need for clarithromycin susceptibility testing for primary treatment (Official Statement of American Thoracic Society - Am J Respir Crit Care Med Vol. 156. pp. S1S25, 1997)

Mycobacterium avium complex: disseminated disease

ART initiated simultaneously or within 1-2 weeks of MAC Rx

US CDC MMWR Dec 17, 2004

Cryptococcal meningitis
Cryptococcal Ag titers partially correlated with treatment response in HIV-infected patients
Clin Infect Dis 1994 May;18(5):789-792.

Cryptococcal meningitis (specific) treatment problem for Thailand

5-flucytosine not available Monotherapy with high-dose Amphotericin B - ?adequate AmB + 400 mg/d fluconazole not sig. different from AmB alone AmB + 800-1,200 mg/d fluconazole V.S. AmB alone still ongoing (multicenter trials)