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