Discontinuation of Trimethoprim-sulfamethoxazole Prophylaxis in Adults on Antiretroviral Therapy in Kenya

HIV Infections Clinical Trial

Official title:

Discontinuation of Trimethoprim-sulfamethoxazole Prophylaxis in Adults on Antiretroviral Therapy in Kenya: a Randomized Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01425073
• Other study ID #: 40461-B
• Status: Completed
• Phase: N/A
• First received: August 25, 2011
• Last updated: April 9, 2014
• Start date: February 2012
• Est. completion date: October 2013

Study information

• Verified date: April 2014
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardKenya: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Both antiretroviral therapy (ART) and prevention of opportunistic infections (OIs) have been associated with significantly decreased mortality in HIV-infected individuals. Trimethoprim-sulfamethoxazole (TMP/SMZ), also known as bactrim, is a common antibiotic and used as prophylaxis for OIs. For countries with high prevalence of HIV and limited health infrastructure, the WHO endorses universal TMP/SMZ for all HIV-infected individuals. Notably, these guidelines were created prior to the scale-up of ARTs. Following ART and subsequent immune recovery, TMP/SMZ may no longer be required. In the US and Europe, for example, TMP/SMZ is discontinued after patients show evidence of immune recovery. Therefore, we propose a prospective randomized trial among HIV infected individuals on ART with evidence of immune recovery (ART for > 18mo and CD4 >350 cells/mm3) to determine whether continued TMP/SMZ prophylaxis confers benefits in decreasing morbidity (malaria, pneumonia, diarrhea), mortality, CD4 count maintenance, ART treatment failure and malaria immune responses.

Description:

Please see summary above.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants must be at least 18 years of age.

• Participants must be willing to participate and give written informed consent.

• Participants must be willing and able to return for the scheduled follow-up visits.

• Participants must have been on ART for > 18 months.

• Participants must have a CD4 count of > 350 cells/mm3.

• Participants must not be suspected of ART treatment failure.

Exclusion Criteria:

• Participants must not be pregnant at enrollment (by urine HCG testing).

• Participants must not be breastfeeding at the time of enrollment.

• Participants must be on first-line ART therapy as defined by Kenyan National Guidelines.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• Diarrhea
• Disease Progression
• HIV Infections
• Immune System Diseases
• Immunologic Deficiency Syndromes
• Infection
• Infectious Disorder of Immune System
• Malaria
• Parasitic Diseases
• Pneumonia

Intervention

Other:
• Discontinue TMP/SMZ prophylaxis
Subjects in the intervention arm will discontinue use of daily TMP/SMZ for the duration of the study

Locations

Country	Name	City	State
Kenya	Homa Bay District Hospital	Homa Bay	Nyanza Pronvince
Kenya	Kombewa District Hospital	Kombewa	Nyanza

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Kenya Medical Research Institute

Country where clinical trial is conducted

Kenya, 

References & Publications (11)

Anglaret X, Chêne G, Attia A, Toure S, Lafont S, Combe P, Manlan K, N'Dri-Yoman T, Salamon R. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet. 1999 May 1;353(9163):1463-8. — View Citation

Furrer H, Egger M, Opravil M, Bernasconi E, Hirschel B, Battegay M, Telenti A, Vernazza PL, Rickenbach M, Flepp M, Malinverni R. Discontinuation of primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1-infected adults treated with combination antiretroviral therapy. Swiss HIV Cohort Study. N Engl J Med. 1999 Apr 29;340(17):1301-6. — View Citation

Hamel MJ, Greene C, Chiller T, Ouma P, Polyak C, Otieno K, Williamson J, Shi YP, Feikin DR, Marston B, Brooks JT, Poe A, Zhou Z, Ochieng B, Mintz E, Slutsker L. Does cotrimoxazole prophylaxis for the prevention of HIV-associated opportunistic infections select for resistant pathogens in Kenyan adults? Am J Trop Med Hyg. 2008 Sep;79(3):320-30. — View Citation

Lowrance D, Makombe S, Harries A, Yu J, Aberle-Grasse J, Eiger O, Shiraishi R, Marston B, Ellerbrock T, Libamba E. Lower early mortality rates among patients receiving antiretroviral treatment at clinics offering cotrimoxazole prophylaxis in Malawi. J Acquir Immune Defic Syndr. 2007 Sep 1;46(1):56-61. — View Citation

McNaghten AD, Hanson DL, Jones JL, Dworkin MS, Ward JW. Effects of antiretroviral therapy and opportunistic illness primary chemoprophylaxis on survival after AIDS diagnosis. Adult/Adolescent Spectrum of Disease Group. AIDS. 1999 Sep 10;13(13):1687-95. Erratum in: AIDS 2000 Aug 18;14(12):1877. — View Citation

Mermin J, Lule J, Ekwaru JP, Malamba S, Downing R, Ransom R, Kaharuza F, Culver D, Kizito F, Bunnell R, Kigozi A, Nakanjako D, Wafula W, Quick R. Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda. Lancet. 2004 Oct 16-22;364(9443):1428-34. — View Citation

Phillips-Howard PA, Nahlen BL, Kolczak MS, Hightower AW, ter Kuile FO, Alaii JA, Gimnig JE, Arudo J, Vulule JM, Odhacha A, Kachur SP, Schoute E, Rosen DH, Sexton JD, Oloo AJ, Hawley WA. Efficacy of permethrin-treated bed nets in the prevention of mortality in young children in an area of high perennial malaria transmission in western Kenya. Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):23-9. — View Citation

Piaggio G, Elbourne DR, Altman DG, Pocock SJ, Evans SJ; CONSORT Group. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA. 2006 Mar 8;295(10):1152-60. Erratum in: JAMA. 2006 Oct 18;296(15):1842. — View Citation

Walker AS, Ford D, Gilks CF, Munderi P, Ssali F, Reid A, Katabira E, Grosskurth H, Mugyenyi P, Hakim J, Darbyshire JH, Gibb DM, Babiker AG. Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort. Lancet. 2010 Apr 10;375(9722):1278-86. doi: 10.1016/S0140-6736(10)60057-8. Epub 2010 Mar 27. — View Citation

Weverling GJ, Mocroft A, Ledergerber B, Kirk O, Gonzáles-Lahoz J, d'Arminio Monforte A, Proenca R, Phillips AN, Lundgren JD, Reiss P. Discontinuation of Pneumocystis carinii pneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection. EuroSIDA Study Group. Lancet. 1999 Apr 17;353(9161):1293-8. — View Citation

Wiktor SZ, Sassan-Morokro M, Grant AD, Abouya L, Karon JM, Maurice C, Djomand G, Ackah A, Domoua K, Kadio A, Yapi A, Combe P, Tossou O, Roels TH, Lackritz EM, Coulibaly D, De Cock KM, Coulibaly IM, Greenberg AE. Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial. Lancet. 1999 May 1;353(9163):1469-75. Erratum in: Lancet 1999 Jun 12;353(9169):2078. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of severe infectious morbidity (malaria, pneumonia, diarrhea)	A combined outcome of malaria, pneumonia or severe diarrhea.	12 months	No
Secondary	CD4 count increase	CD4 count increase	12 months	No
Secondary	Rate of ART treatment failure	Rate of ART treatment failure	12 months	No