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Supplements Addressing Adherence Challenges Associated With Antiretroviral Therapy: Focus on Noninfectious Diarr
Participating Faculty: Addressing Adherence Challenges Associated With Antiretroviral Therapy: Focus on Noninfectious Diarrhea
The Importance of Treatment Adherence in HIV
Kenneth L. Schaecher, MD, FACP, CPC
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Management of Noninfectious Diarrhea Associated With HIV and Highly Active Antiretroviral Therapy
Rodger D. MacArthur, MD

Management of Noninfectious Diarrhea Associated With HIV and Highly Active Antiretroviral Therapy

Rodger D. MacArthur, MD
The safety data, which included study subjects from both the first and second phases of the study (crofelemer n = 130, placebo n = 137), showed that the percentages of patients who experienced any adverse event (AE) were similar in the crofelemer and placebo groups (34.6% crofelemer vs 32.8% placebo), and the rate of serious AEs was very low and similar for both groups (1.5% crofelemer vs 2.9% placebo). There were 4 serious AEs (any cause) in the placebo group and 2 in the crofelemer group, and 4 AE-related discontinuations in the placebo group compared with none in the crofelemer group. GI effects and infections were the most common AEs in both groups, and 2 cases each of the following AEs were observed in the crofelemer group: dyspepsia, flatulence, abdominal pain, hemorrhoids, and constipation. Upper respiratory tract infections were seen in 5 crofelemer and 4 placebo patients, while urinary tract infections were seen in 3 crofelemer patients and 1 placebo patient.31

Other Non-Approved and Non-Pharmacologic Treatments

Octreotide—The somatostatin analogue octreotide has demonstrated efficacy in patients with HIV and AIDS experiencing diarrhea. However, studies of octreotide have largely been conducted in the pre-HAART era, and do not reflect treatment of HAART-induced diarrhea.33-35

Racecadotril—The enkephalinase inhibitor racecadotril (also known as acetorphan) has demonstrated efficacy in small studies of patients with HIV experiencing diarrhea, but the data are limited and do not reveal the efficacy of racecadotril in HAART-related diarrhea.34,36

Bovine colostrum—Bovine colostrum has been shown to alleviate diarrhea in HIV-positive patients in several studies. However, these studies were conducted in patients who were, for the most part, not receiving HAART, or whose diarrhea predated initiation of HAART, and its efficacy in HAART-treated patients is therefore unclear.37-39

Curcumin—Curcumin (extracted from turmeric) as a treatment for HIV-related diarrhea was evaluated in a nonblinded, non-controlled study by the Southern California Kaiser Permanente Medical Group in 8 patients in whom no pathogen or parasite was detected by stool culture or observation or by endoscopy or colonoscopy. Seven of the 8 subjects were receiving HAART. The mean number of bowel movements before therapy was 6.75, which was reduced to 1.69 by the end of therapy (P = .006). Time to resolution varied from 3 to 28 days; side effects were minimal and not serious.40

Lactobacillus rhamnosus GG—The effects of the probiotic Lactobacillus rhamnosus GG (LGG) were evaluated in 17 patients with HIV-related diarrhea in a randomized, placebo-controlled study with crossover design (2 weeks on LGG and 2 weeks on placebo) conducted in Finland. Neither daily stool frequency nor bowel movements were statistically different between LGG and placebo, nor did LGG improve stool consistency.41

Summary

The success of HAART in reducing HIV/AIDS morbidity and mortality also conferred a substantial reduction in the risk of the kind of opportunistic infection that can ravage patients and considerably speed their deterioration. The success of these treatments should not, however, overshadow the fact that diarrhea remains a serious problem in the HAART era, particularly with regard to certain drugs and drug classes. Diarrhea can adversely impact QoL. Knowledge of the serious impact of diarrhea in patients with HIV should prompt the selection of therapies to minimize diarrhea risk. In cases when diarrhea is unavoidable, the recent approval of crofelemer provides a therapeutic option for a substantial proportion of the affected patient population.

Author affiliations: Department of Internal Medicine, Division of Infectious Diseases, Wayne State University and Wayne State University HIV/AIDS Clinical Research Unit, Detroit, MI.
Funding source: This supplement was supported by Salix Pharmaceuticals, Inc.
Author disclosure: Dr MacArthur reports providing expert testimony on behalf of Salix Pharmaceuticals, Inc. He also reports meeting/conference attendance with Salix Pharmaceuticals, Inc.
Authorship information: Concept and design; acquisition of data; analysis and interpretation of data; critical revision of the manuscript for important intellectual content; and supervision.
Address correspondence to: Rodger D. MacArthur, MD, WSU Tolan Park Medical Building, 3901 Chrysler Service Drive, Suite 4B, Detroit, MI. E-mail: macarthur@wayne.edu.
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