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

Conditions

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

Keywords

HIV, Co-Infections, Malaria, Pneumonia, Diarrhea

Brief 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.

Detailed description

Please see summary above.

Dennis W. Juma, Peninah Muiruri, Krista Yuhas, Grace John‐Stewart, Ronald K. Ottichilo et al. (9 authors)

PLoS neglected tropical diseases2019-03-2125 citations

10.1371/journal.pntd.0007223

Malaria Parasitemia and Parasite Density in Antiretroviral-Treated HIV-Infected Adults Following Discontinuation of Cotrimoxazole Prophylaxis

Ronald K. Ottichilo, Christina S. Polyak, Bernard Guyah, Benson Singa, Josphat Nyataya et al. (8 authors)

The Journal of Infectious Diseases2016-10-1911 citations

10.1093/infdis/jiw495

Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial

Christina S. Polyak, Krista Yuhas, Benson Singa, Monica Khaemba, Judd L. Walson et al. (7 authors)

PLoS Medicine2016-01-0533 citations

10.1371/journal.pmed.1001934

Interventions

OTHERDiscontinue TMP/SMZ prophylaxis

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
Incidence of severe infectious morbidity (malaria, pneumonia, diarrhea)	12 months	A combined outcome of malaria, pneumonia or severe diarrhea.

Secondary

Measure	Time frame	Description
CD4 count increase	12 months	CD4 count increase
Rate of ART treatment failure	12 months	Rate of ART treatment failure

Countries

Kenya

Outcome results

None listed