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

NCT ID: NCT01425073

Last Updated: 2014-04-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-29

Study Completion Date

2013-10-31

Brief Summary

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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.

Detailed Description

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Please see summary above.

Conditions

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HIV Infections Acquired Immunodeficiency Syndrome Disease Progression Immune System Diseases Malaria Parasitic Diseases Pneumonia Diarrhea Infectious Disorder of Immune System

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Stop TMP/SMZ

Arm 1 will have patients discontinue trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis; patients will follow up every 3 months with study staff.

Group Type EXPERIMENTAL

Discontinue TMP/SMZ prophylaxis

Intervention Type OTHER

Subjects in the intervention arm will discontinue use of daily TMP/SMZ for the duration of the study

Standard of care TMP/SMZ prophylaxis

Arm 2 will continue standard of care treatment with trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Discontinue TMP/SMZ prophylaxis

Subjects in the intervention arm will discontinue use of daily TMP/SMZ for the duration of the study

Intervention Type OTHER

Other Intervention Names

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Septrin Septra Cotrimoxazole Bactrim

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kenya Medical Research Institute

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Christina Polyak

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Christina Polyak, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Kenya Medical Research Institute/ Department of Medicine, University of Washington

Locations

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Homa Bay District Hospital

Homa Bay, Nyanza Pronvince, Kenya

Site Status

Kombewa District Hospital

Kombewa, Nyanza, Kenya

Site Status

Countries

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Kenya

References

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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. doi: 10.1097/00002030-199909100-00012.

Reference Type BACKGROUND
PMID: 10509570 (View on PubMed)

Anglaret X, Chene 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, Cote d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet. 1999 May 1;353(9163):1463-8. doi: 10.1016/s0140-6736(98)07399-1.

Reference Type BACKGROUND
PMID: 10232311 (View on PubMed)

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, Cote d'Ivoire: a randomised controlled trial. Lancet. 1999 May 1;353(9163):1469-75. doi: 10.1016/s0140-6736(99)03465-0.

Reference Type BACKGROUND
PMID: 10232312 (View on PubMed)

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. doi: 10.1016/S0140-6736(04)17225-5.

Reference Type BACKGROUND
PMID: 15488218 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18784222 (View on PubMed)

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. doi: 10.1056/NEJM199904293401701.

Reference Type BACKGROUND
PMID: 10219064 (View on PubMed)

Weverling GJ, Mocroft A, Ledergerber B, Kirk O, Gonzales-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. doi: 10.1016/s0140-6736(99)03287-0.

Reference Type BACKGROUND
PMID: 10218526 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17972365 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20347483 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12749482 (View on PubMed)

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. doi: 10.1001/jama.295.10.1152.

Reference Type BACKGROUND
PMID: 16522836 (View on PubMed)

Juma DW, Muiruri P, Yuhas K, John-Stewart G, Ottichilo R, Waitumbi J, Singa B, Polyak C, Kamau E. The prevalence and antifolate drug resistance profiles of Plasmodium falciparum in study participants randomized to discontinue or continue cotrimoxazole prophylaxis. PLoS Negl Trop Dis. 2019 Mar 21;13(3):e0007223. doi: 10.1371/journal.pntd.0007223. eCollection 2019 Mar.

Reference Type DERIVED
PMID: 30897090 (View on PubMed)

Ottichilo RK, Polyak CS, Guyah B, Singa B, Nyataya J, Yuhas K, John-Stewart G, Waitumbi JN. Malaria Parasitemia and Parasite Density in Antiretroviral-Treated HIV-Infected Adults Following Discontinuation of Cotrimoxazole Prophylaxis. J Infect Dis. 2017 Jan 1;215(1):88-94. doi: 10.1093/infdis/jiw495. Epub 2016 Oct 25.

Reference Type DERIVED
PMID: 28077587 (View on PubMed)

Polyak CS, Yuhas K, Singa B, Khaemba M, Walson J, Richardson BA, John-Stewart G. Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial. PLoS Med. 2016 Jan 5;13(1):e1001934. doi: 10.1371/journal.pmed.1001934. eCollection 2016 Jan.

Reference Type DERIVED
PMID: 26731191 (View on PubMed)

Other Identifiers

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40461-B

Identifier Type: -

Identifier Source: org_study_id

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