Antituberculosis drug resistance and anonymous HIV surveillance in TB patients

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HIV-TB Model The Botswana experience By E.M.
Lungu (UB) M. Kgosimore (BCA) F. Nyabadza
(UB) Modeling Disease in Africa Workshop 25 27
June 2007, Stellenbosch, S.A.
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• Botswana implemented 100 coverage of DOTS in
  1986. Since 1986 all individuals
• who tested positive were enrolled for the
  anti-TB program.
• For new patients
• Treatment consists of 2 months of isoniazid H,
  rifampicin R, pyrazinamide Z, and ethambutol
  E 2HRZE followed by 4 months of isoniazid and
  rifampicin 4HR
• Re-treatment Patients
• The re-treatment regimen is 2HRZES/1HRZE/5HRE
• Both treatments for new or recurrent TB are the
  best standard regimens recommended.
• Despite this the number of TB cases increased by
  120 between 1986 1nd 1989.

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• In the first drug-resistance survey in 1995, of
  the 44 of patients with tuberculosis, 49 were
  HIV infected.
• In 2002, the case detection rate in Botswana was
  88, of which 78 of patients completed treatment
  and 6 interrupted treatment.
• In 2002, a third survey was undertaken to
  determine trends in anti-tuberculosis drug
  resistance in patients with tuberculosis and to
  provide a nationwide estimate of HIV infection in
  such patients.

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PATIENT DISTRIBUTION

• 2002 survey

PATIENTS 2425
RETREAMENT PATIENTS 429 (17.2)
NEW PATIENTS 1990 (82)
UKNOWN STATUS 6 (0.2)
SMEAR POSITIVE 210 (49)
SMEAR NEGATIVE 219 (51)
HIV POSITIVE 1457(60)
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PATIENTS TB STATUS
Sample Size 2425
POSITIVE FOR MYCOBACTERIA 1481 (61)
NEGATIVE MYCOBACTERIA 944 (39)
POSITIVE M TUBERCULOSIS 1288 (87)
LATENT M TB 193 (13)
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• Drug resistance results
• For new patients 1995 1999
  2002
• n430 n638 n1182
• Any Drug Res 16(3.7) 40(6.3) 123(10.4)
• Isoniazid 7(1.6) 28(4.4) 53(4.5)
• Rifampicin 4(0.9) 4(0.6) 24(2.0)
• Ethambutol 0 1(0.2)
  15(1.3)
• Streptomycin 6(1.5) 14(2.2)
  82(6.9)

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• Monores 15(3.5) 34(5.3) 86(7.3)
• Isoniazid 6(1.4) 23(3.6) 22(1.9)
• Rifampicin 3(0.7) 1(0.2) 10(0.8)
• Ethambutol 0 0 2(0.2)
• Streptomycin 6(1.5) 10(1.6)
  52(6.9)
• Multidrugres 1(0.7) 3(0.5) 10(0.8)
  

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• Prev treated cases
• 1995-96 1999 2002
• n121 n145 n106
• Drug Res 18(15) 33(23) 24(23)
• Isoniazid 12(10) 24(27) 15(14)
• Rifampicin 10(8) 19(24) 13(12)
• Ethambutol 6(5.3) 4(3) 9(9)
• Streptomycin 10(9) 7(5) 17(16)

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• Monoresistance
• Mono Res 9(7.4) 18(12.4) 7(6.6)
• Isoniazid 4(3.3) 9(6.2) 0
• Rifampicin 2(1.7) 6(4.1) 0
• Ethambutol 0 0 2(1.9)
• Streptomycin 3(2.5) 3(2.1) 5(4.7)
  
• Multidrugres 7(6.1) 13(9.0) 11(10.4)

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• Significant increases were recorded for
  resistance to any drug and for resistance to
  isoniazid, streptomycin, ethambutol, or
  rifampicin in new patients.
• The proportion of tuberculosis multidrug
  resistance in new patients remained low, although
  results from the three surveys suggest an
  increasing trend.
• The reports (1995, 1999, 2002) show a trend of
  rising resistance to at least one drug in new
  patients from 3.7 in 1995 to 10.4 in 2002 and
  an HIV prevalence of 60 in patients with TB.

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• The increasing trend to TB drugs has implications
  for TB control and HIV treatment.
• We illustrate this with the following examples

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The American report on incidence in Sub-Sahara
Africa
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• Poor absorption of both TB and HIV medication may
  be causing mutations in the HIV virus.
• The following examples illustrate this point.

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• A study of 23 patients in Botswana on one of the
  baseline regimen and who met the requirement for
  a drug resistance test
• Either
• (a) DDI 3TC Nevirapine
• NRTI NRTI Nevirapine
• Or
• (b) D4T 3TC Nevirapine
• NRTI NRTI Nevirapine
• 14. Of 15 patients who discontinued treatment
• Seven patients were found to possess the mutant
  virus K65R

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• Study by Gallant et el (2006) comparing two
  regimens involving 35 patients
• Regimen 1. TDF emtricitabine efavirenz
• NRTI NRTI NNRTI
• (12 Patients)
• Regimen 2. AZT 3TC efavirenz
• NRTI NRTI NNRTI
• (23 Patients)
• On Regimen 1 2 developed M184V/I mutations
• On Regimen 2. 7 developed M184V/I mutations

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• We believe that 100 coverage of DOTS may be
  contributing to the problem.
• Careful screening must be implemented before
  DOTS.
• We develop a model to evaluate the advantages of
  screening.

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• MODEL DIAGRAM

S
I2
I1
I4
I3
I6
I5
A2
A1
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Plots of Susceptibles/Infectives over time
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Phase portraits
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Plots of New Infections vs Prevalence
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Tragectories for Infectives and AIDS Populations
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Discussion and Conclusions
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