HIV-TB Model: The Botswana experience By E.M. Lungu (UB) M. Kgosimore (BCA) F. Nyabadza (UB)...
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Transcript of HIV-TB Model: The Botswana experience By E.M. Lungu (UB) M. Kgosimore (BCA) F. Nyabadza (UB)...
HIV-TB Model: The Botswana experience
By
E.M. Lungu (UB)M. Kgosimore (BCA)
F. Nyabadza (UB)
Modeling Disease in Africa Workshop25 – 27 June 2007, Stellenbosch, S.A.
• 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.
• 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.
PATIENT DISTRIBUTION
2002 survey
PATIENTS2425
NEWPATIENTS
1990(82%)
RETREAMENTPATIENTS
429 (17.2%) UKNOWNSTATUS6 (0.2%)
SMEARPOSITIVE210 (49%)
SMEARNEGATIVE219 (51%)
HIVPOSITIVE1457(60%)
PATIENTS TB STATUS
SampleSize2425
POSITIVE FORMYCOBACTERIA
1481 (61%)NEGATIVE
MYCOBACTERIA944 (39%)
POSITIVEM
TUBERCULOSIS1288 (87%)
LATENT MTB
193 (13%)
• Drug resistance results• For new patients: 1995 1999 2002• n=430 n=638 n=1182• 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%)
•• 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%)
• Prev treated cases: – 1995-96 1999
2002
• n=121 n=145 n=106• Drug Res 18(15%) 33(23%) 24(23%)• Isoniazid 12(10%) 24(27%) 15(14%)• Rifampicin 10(8%) 19(24%) 13(12%)• Ethambutol6(5.3%) 4(3%) 9(9%)• Streptomycin 10(9%) 7(5%) 17(16%)
• 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• Ethambutol0 0 2(1.9%)• Streptomycin 3(2.5%) 3(2.1%) 5(4.7%) • Multidrugres 7(6.1%) 13(9.0%)
11(10.4%)
• 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.
• The increasing trend to TB drugs has implications for TB control and HIV treatment.
• We illustrate this with the following examples:
The American report on incidence in Sub-Sahara Africa
• Poor absorption of both TB and HIV medication may be causing mutations in the HIV virus.
• The following examples illustrate this point.
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 + Nevirapine14. Of 15 patients who discontinued treatment Seven patients were found to possess the mutant virus K65R
• 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 mutationsOn Regimen 2. 7 developed M184V/I mutations
• 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.
• MODEL DIAGRAM
S
I1 I2
I3I4
I5I6
A1A2
Plots of Susceptibles/Infectives over time
Phase portraits
Plots of New Infections vs Prevalence
Tragectories for Infectives and AIDS Populations
Discussion and Conclusions