When to Initiate Highly Active Antiretroviral Therapy in Sub-Saharan Africa? A South African Cost-Effectiveness Study

Abstract

Background

Large-scale programmes increasing access to highly active antiretroviral therapy (HAART) are being implemented in sub-Saharan Africa. However, cost-effectiveness of initiating treatment at different CD4 count thresholds has not been explored in resource-poor settings.

Methods

A cost-effectiveness analysis was conducted from a public health perspective using primary treatment outcomes, healthcare utilisation and cost data (Jan 2004 local prices; US$1=7.6 Rands) derived from the Cape Town AIDS Cohort. A Markov state-transition model was developed to estimate life-expectancy, lifetime costs, quality-adjusted life-years (QALYs), cost per life-year and QALY gained for initiating HAART at three CD4 cell count thresholds (<200/μl, 200–350/μl and >350/μl), including the no antiretroviral therapy (No-ART) alternative. Each treatment option was compared with the next most effective undominated option.

Results

Mean life-expectancy was 6.2, 18.8, 21.0 and 23.3 years; discounted (8%) QALYs were 3.1, 6.2, 6.7 and 7.4; and discounted lifetime costs were US$5,250, US$5,434, US$5,740, US$6,588 for No-ART, and therapy initiation at <200/μl, 200–350/μl and >350/μl scenarios respectively. Clinical benefits increased significantly with early therapy initiation. Initiating therapy at <200/μl had an incremental cost-effectiveness ratio (ICER) of US$54 per QALY versus No-ART, 200–350/μl had an ICER of US$616 versus therapy initiation at <200/μl, and >350/μl had an ICER of US$1,137 versus therapy initiation at 200–350/μl ICERs were sensitive to HAART cost.

Conclusions

HAART is reasonably cost-effective for HIV-infected patients in South Africa, and most effective if initiated when CD4 count >200/μl. Deferring treatment to <200/μl would reduce the aggregate cost of treatment, but this should be balanced against the significant clinical benefits associated with early therapy.

References

Time to hit HIV, early and hard.

New Engl J Med 1995; 333: 450–451.

Lane

H.C.

, Neaton

J.D.

When to start therapy for HIV infection: a swinging pendulum in search of data.

Ann Intern Med 2003; 138: 680–681.

Holmberg

S.D.

, Palella

F.J.

Jr. , Lichtenstein

K.A.

, Havlir

D.V.

The case for earlier treatment of HIV infection.

Clin Infect Dis 2004; 39: 1699–1704.

World Health Organization. Scaling up antiretroviral therapy in resource-limited settings: Treatment guidelines for a public health approach; 2003 [cited 2005 Feb]. Available from: http://www.who.int/hiv/pub/prev_care/en/arvrevision2003en.pdf. Accessed February 2005.

Yeni

P.G.

, Hammer

S.M.

, Hirsch

M.S.

Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA Panel.

JAMA 2004; 292: 251–265.

Department of Health and Human Services (DHHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. October, 2005. http://www.thebody.com/hivatis/pdfs/adult_guide.pdf. Accessed December 2005.

European AIDS Clinical Society (EACS). European guidelines for the clinical management and treatment of HIV infected adults in Europe; 2001 [cited 2005 March]. http://www.eacs.ws/download/European_Treatment_Guidelines.pdf.

The British HIV Association (BHIVA). BHIVA guidelines for the treatment of HIV-infected adults with antiretroviral therapy; 2003 [cited 2004 Dec]. Available from: http://www.bhiva.org/guidelines/2003/hiv.

Freedberg

K.A.

, Losina

, Weinstein

M.C.

The cost effectiveness of combination antiretroviral therapy for HIV disease.

New Engl J Med 2001; 344: 824–831.

10.

Schackman

B.R.

, Freedberg

K.A.

, Weinstein

M.C.

Cost-effectiveness implications of the timing of antiretroviral therapy in HIV-infected adults.

Arch Intern Med 2002; 25: 2478–2486.

11.

Sendi

P.P.

, Bucher

H.C.

, Harr

Cost-effectiveness of highly antiretroviral therapy in HIV-infected patients: Swiss HIV cohort study.

AIDS 1999; 13: 1115–1122.

12.

Sterling

T.R.

, Chaisson

R.E.

, Moore

R.D.

HIV-1 RNA, CD4 T-lymphocytes, and clinical response to highly active antiretroviral therapy.

AIDS 2001; 23: 2251–2257.

13.

Hogg

R.S.

, Yip

, Chan

K.J.

Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy.

JAMA 2001; 286: 2568–2577.

14.

Palella

F.J.

Jr. , Deloria-Knoll

, Chmiel

J.S.

HIV Outpatient Study Investigators. Survival benefit of initiating antiretroviral therapy in HIV-infected persons in different CD4⁺ cell strata.

Ann Intern Med 2003; 138: 620–626.

15.

Phillips

A.N.

, Lepri

A.C.

, Lampe

, Johnson

, Sabin

C.A.

When should antiretroviral therapy be started for HIV infection? Interpreting the evidence from observational studies.

AIDS 2003; 17: 1863–1869.

16.

Grant

A.D.

, Djomand

, De Cock

K.M.

Natural history and spectrum of disease in adults with HIV/AIDS in Africa.

AIDS 1997; 11: 43–54.

17.

Badri

, Ehrlich

, Wood

, Pulerwitz

, Maartens

Tuberculosis should not be considered an AIDS-defining illness in areas with a high tuberculosis prevalence.

Int J Tuberc Lung Dis 2002; 6: 231–237.

18.

Holmes

C.B.

, Losina

, Walensky

R.P.

, Yazdanpanah

, Freedberg

K.A.

Review of human immunodeficiency virus type 1-related opportunistic infections in sub-Saharan Africa.

Clin Infect Dis 2003; 36: 652–662.

19.

Maartens

Opportunistic infections associated with HIV infection in Africa.

Oral Dis 2002; 8: 76–79.

20.

Badri

, Ehrlich

, Wood

, Pulerwitz

, Maartens

Association between tuberculosis and HIV disease progression in a high tuberculosis prevalence area.

Int J Tuberc Lung Dis 2001; 5: 225–232.

21.

Badri

, Wilson

, Wood

Effect of highly active antiretroviral therapy on incidence of tuberculosis in South Africa: a cohort study.

Lancet 2002; 359: 2059–2064.

22.

Blanckenberg

D.H.

, Wood

, Horban

Compact Highly Active Antiretroviral Medication Study. A phase III open-label randomized, multicentre study to evaluate the efficacy and tolerability of adding nevirapine and/or hydroxyurea to a triple-nucleoside-based antiretroviral drug regimen in treatment-naïve HIV-1 infected subjects.

AIDS 2004; 18: 631–640.

23.

Leth

F.V.

, Phanuphak

, Ruxrungtham

The 2NN Study: Comparison of first-line antiretroviral therapy with regimens including nerirapine, efavirenz or both drugs combined, together with stavudine and lamivudine: A randomised open-label trial, the 2NN Study.

Lancet 2004; 363: 1248–1250.

24.

Wood

, Phanuphak

, Cahn

Long-Term Efficacy and Safety of Atazanavir in Combination with Stavudine and Lamivudine in Patients Previously treated with Nelfinavir or Atazanavir.

J Acquire Immune Defic Syndr 2004; 36: 684–692.

25.

Gathe

J.C.

, Ive

, Wood

SOLO: 48 week efficacy and safety comparison of once-daily fosamprenavir/ritonavir vs twice daily nelfinavir in naïve HIV-1-infected patients.

AIDS 2004; 18: 1529–1537.

26.

Wood

, Arasteh

, Teofilo

, Trepo

, Livrozet

J-M

. A 42-week open-label study to assess the pharmacokinetics, antiretroval activity and safety of amprenavir or amprenavir plus ritonavir in combination with abacavir and lamivudine for treatment of HIV-infected patients. Clin Infect Dis 2004; 39: 591–594.

27.

Govender

, McIntyre

, Grimwood

, Maartens

The costs and perceived quality of care for people living with HIV/AIDS in the Western Cape Province in South Africa. Small-Applied Research No. 14. Bethesda (Maryland): Partnerships for Health Reform Project, Abt Associates; April 2000 [cited 2005 Oct]. http://www.phrplus.org/Pubs/sar14.pdf.

28.

Brouwer

, Rutten

, Koopmanschap

Costing in Economic Evaluation, in Economic Evaluation in Health Care: Merging Theory with Practice, 2001; pp. 68–93. Edited by Drummond

, and McGuire

, Oxford: Oxford University Press.

29.

Conteh

, Walker

Cost and unit-cost calculations using step-down accounting.

Health Policy Plan 2004; 19: 127–135.

30.

Statistics South Africa. Historical PPI key indicators; December 2004 [cited March 2004]. Available from: http://www.statssa.gov.za/keyindicators/CPI/CPIHistory.pdf.

31.

US Federal Reserve Board. Foreign exchange rates. South Africa Historical Rates; 2005 [cited 2005 Oct]. Available from: http://www.federalreserve.gov/releases/H10/hist/dat00_sf.htm.

32.

Cleary

, Boulle

, McIntyre

, Coetzee

Cost-effectiveness of antiretroviral treatment for HIV-positive adults in a South African township. 2004, Health Systems Trust: Durban. http://www.hst.org.za/publications/579.

33.

National Department of Health. National antiretroviral treatment guidelines. National Department of Health South Africa, 2004 [cited 2004 August]. Available from: http://www.aidsinfo.co.za/uploadfiles/PDF/DH16_ART_Guidelines.pdf.

34.

Koch

R.J.

The Quantum Year Book. Port Elizabeth: Van Zyl, Rudd & Associates; 2003.

35.

Gold

M.R.

, Siegel

J.E.

, Russell

L.B.

, Weinstein

M.C.

(eds). Cost effectiveness in Health and Medicine. New York: Oxford University Press; 1996.

36.

Drummond

, Jefferson

T.O.

Guidelines for authors and peer reviewers of economic submissions to the BMJ.

BMJ 1996; 313: 275–283.

37.

O'Keefe

E.A.

, Wood

The impact of human immunodeficiency virus (HIV) infection on quality of life in a multiracial South African population.

Qual Life Res 1996; 5: 275–280.

38.

Pitt

, Badri

, Wood

Changes in quality of life in a South African antiretroviral programme. 16th International AIDS Conference. 12–16 July 2004, Bangkok Thailand. Abstract MoPeD3782.

39.

Brazier

, Roberts

, Deverill

The estimation of a preference-based measure for health from the SF-36.

J of Health Econ 2002; 21: 271–292.

40.

National Institute for Clinical Excellence. Guide to the Methods of Technology Appraisal. NICE: London, April 2004 [cited November 2005]. Available from: http://www.nice.org.uk/pdf/TAP_Methods.pdf.

41.

O'Hagan

, Luce

B.R.

A Primer on Bayesian Statistics in Health Economics and Outcomes Research. 2003: MEDTAP International.

42.

WHO. Report of the Commission on Macroeconomics and Health. Geneva: World Health Organization, 2002.

43.

Sterling

T.R.

, Chaisson

R.E.

, Keruly

, Morre

R.D.

Improved outcomes with earlier initiation of highly active antiretroviral therapy among Human Immunodeficiency Virus-infected patients who achieve durable virologic suppression: longer follow-up of an observational cohort study.

J Infect Dis 2003; 188: 1659–1665.

44.

Badri

, Bekker

L.G.

, Orrell

, Pitt

, Cilliers

, Wood

Initiating highly active antiretroviral therapy in sub-Saharan Africa: an assessment of the revised World Health Organization scaling-up guidelines.

AIDS 2004; 18: 1159–1168.

45.

Keiser

, Taffe

, Zwahlen

All cause mortality in the Swiss HIV Cohort Study from 1990 to 2001 in comparison with the Swiss population.

AIDS 2004; 18: 1835–1843.

46.

Egger

, May

, Chene

, Phillips

A.N.

, Ledergerber

, Dabis

Prognosis of HIV-1 infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies.

Lancet 2002; 360: 119–129.

47.

Guinness

, Arthur

, Bhatt

, Achiya

, Kariuki

, Gilks

Cost of hospital care for HIV-positive and HIV-negative patients at Kenyatta National Hospital, Nairobi, Kenya.

AIDS 2002; 16: 901–908.

48.

Olsen

, Richardson

Production gains from health care: what should be included in cost-effectiveness analysis?

Soc Sci Med 1999; 49: 17–26.