The contribution of Operational Research to Improving TB-HIV Control Activities in Malawi

Rhehab ChimziziTB Technical Advisor/TBCAP Country Lead-Ghana

Management Sciences for HealthSTOP TB SYMPOSIUM, CANCUN

December 3, 2009

Presentation outlines

• Key relevant social economical and TB and HIV indicators• What prompted Malawi to implement TB/HIV operation research agenda?• Decisive international TB/HIV study for TB patients that pulled the trigger• UNAIDS Recommendations on the use of CPT in PLHIV• How Malawi responded to the UNAIDS recommendations?• Results of district TB/HIV operational research activities• The Malawi policy on VCT and CPT for TB patients• Positive results from the districts TB/HIV studies to TB control in Malawi and the

world at large• On-going challenges• Acknowledgements

List of Relevant TB and HIV indicators in Malawi

INDICATOR VALUE YEAR SOURCE

Population 13,066,320 2008 NSO, Malawi

Percentage of female population

51% 2008 NSO, Malawi

% below poverty line 53% 2009 World bank

TB notification rate (WHO estimates)

346/100,000 2007 WHO

TB notification rate (actual)

255/100,000 2007 NTP, Malawi

HIV prevalence in the general population

12% 2008 UNAIDS

HIV prevalence among TB patients

69% 2007 WHO/NTP

The Rationale for implementing TB/HIV operational research activities

• A four-fold increase of TB cases (5,334 in 1985 to 20,676 in 1997)

• TB death rates increased (6% in 1987 to 21% in 1996)

• In 2001, 77% of TB patients were HIV positive (surveillance)

• Health systems not offering HIV testing or any basic care and support for PLHIV (ART too expensive before 2003)

• Little collaboration between TB and HIV programs– TB and HIV program pursed different agenda

• Most research just clinically based at the two main referral hospitals

A seminal study: CPT in new HIV+ve TB patients in Cote d’Ivoire

760 HIV-positive smear+ve TB patients on short course chemotherapy one month later - CPT or placebo

CPT associated with 48% lower mortality 44% lower hospitalisation rate

(Wiktor et al Lancet 1999;353: 1469)

UNAIDS 2000 PROVISIONAL RECOMMENDATIONS

CPT be used in adults and children living with AIDS in Africa as part of minimum package of care

Ethical implications

• Unethical to conduct further randomised controlled clinical trials on CPT efficacy in HIV-positive TB patients

• UNAIDS- funded Malawi College of Medicine RCT trial on CPT was stopped after recruiting 37 patients

Malawi MOH Meeting in 2000

• Cotrimoxaxole may not have the same efficacy in Malawi as Cote d’Ivoire because different resistance patterns and different spectrum of HIV-related illness

• Malawi not prepared to adopt WHO/UNAIDS – guidelines on CPT as policy because no evidence of effect and may be dangerous to the first line of anti-malaria treatment (then SP)

• Strong endorsement for district operational research• Operational research studies started / continued in Thyolo, Karonga

and Lilongwe districts on CPT in HIV+ve TB patients

AIM OF DISTRICT STUDIESin Thyolo and Karonga

To determine the feasibility and effectiveness of “VCT and CPT” in reducing case fatality in

a cohort of TB patients registered under routine programme conditions

[Zachariah et al, AIDS 2003 – Thyolo study]

[Mwaungulu et al, Bulletin WHO 2004 – Karonga study]

ANALYSIS: Historical comparison• VCT+CPT group: the cohort offered VCT and

CPT and registered during a full one year period

• Control group: the cohort not on CPT and registered the previous year during a full one year period

Comparison of mortality at the end of treatment between the two groups

REGISTERED TB CASES

Thyolo

VCT-CPT 1061

Control 925

Karonga

VCT-CPT 362

Control 355

Interventions in TB patients

Thyolo

(1061 patients)

Karonga

(362 patients)

HIV tested 91% 73%

HIV-positive 69% 51%

Started CPT 94% 96%

REACTIONS TO CPT

Thyolo:

#. on CPT 693

#. reactions 14 ( 2%)

Karonga:

#. on CPT 153

#. reactions 8 (5%)

Case fatality: all TB types

Thyolo:

VCT-CPT 28%

Control 36%

p < 0.001

Karonga:

VCT-CPT 29%

Control 37%

p < 0.001

Number of TB patients that needed treatment with “VCT and CPT” to

prevent one death = 12in both Thyolo and Karonga

“estimated cost to prevent one death = USD$100”

CONCLUSION

• In the two district based studies, the “package of VCT and CPT” given to patients at or shortly after registration was associated with a significant reduction in case fatality

• Thyolo most effect in smear-ve PTB • Karonga most effect in smear+ve PTB

POLICY RECOMMENDATIONS for TB PATIENTS

• Provision of VCT and CPT in TB patients continues in Thyolo, Karonga

• Continue joint implementation of VCT+ CPT in TB patients in routine programme conditions through the WHO coordinated ProTEST Project in Lilongwe

• Phased scale up of VCT +CPT country-wide

Progress• A three-year HIV-TB scale up plan developed and incorporated

within the NTP 5-year (2002-2006) development plan

• National VCT-CPT guidelines developed

• Training package on VCT and CPT developed and implemented

• CPT procured for HIV-infected TB patients

• M&E system set up

• Regular progress reports through routine quarterly monitoring and annual country wide situation analysis of HIV and TB services

HIV Testing and CPT in TB patients in Malawi: progress

MALAWI 2003 2004 2005 2006 2007

TB patients 26,836 26,136 26,019 26,659 25,767

HIV tested 15% 26% 47% 66% 83%

HIV positive 69% 72% 69% 66% 69%

Started CPT 87% 97% 92% 98% 97%

The rapid HIV test introduced from 2002

CPT introduced from 2002

ART introduced from 2004

National TB treatment outcomes in new smear-positive PTB

Year Treatment Success Death Other

2002 71% 19% 10%

2003 70% 19% 11%

2004 71% 16% 13%

2005 74% 15% 11%

2006 79% 13% 8%

The secret behind the success• TB and HIV programs worked together

• TA to spear head the research agenda and mentor local staff

• Costed HIV-TB plan with operational research as a priority

• Annual national research dissemination workshops

• Publications in local and international peer review journals

• A responsive Ministry of Health and political commitment

• Support from various development partners: USAID, DFID, NORAD, KNCV, WHO and the Global Fund

On-going challenges

• Stock outs of HIV Kits• TB clinics not offering on-site HIV testing /counseling to TB patients• Stock outs of cotrimoxazole tablets despite the GF support• Difficulties in monitoring CPT adherence in the routine program• When to start ART in TB patients still a thorny issue

– Are we waiting to see more TB patients die before we decisively act?

• PLHIV have known for years that IPT is effective in reducing TB incidence, but national programs are still busy with workshops to discus the same issue (Lip service at its best)

• In most national programs operational research is still centralized• Human Resource scarcity

– Time to strongly consider task shifting to reach the largest impact

Acknowledgements

• The Government of United States of America through USAID for supporting me to attend this conference

• The Malawi Government for being responsive to the results of operational research

• District Management Teams in Malawi• Development partners: USAID, DFID, NORAD, KNCV, WHO, and The

Global Fund etc• Prof Anthony Harries now with the Union• Prof Felix Salaniponi now with KNCV in Kenya• Dr Frank Bonsu, NTP Manager in Ghana