Table 2.
Probiotics and Prebiotics in HIV: Methodological Quality of Studiesa
| Reference | Primary Endpoint | Study Design | Selection Bias | Performance Bias | Detection Bias | ITT/PP | Comments |
|---|---|---|---|---|---|---|---|
| Anukam et al [28] | Moderate diarrhea | DB CT | I | I | Unclear | PP | No randomization or allocation described. Research funded in part by Urex Biotech Inc. and Natural Sciences and Engineering Research Council of Canada. |
| Cunningham-Rundles et al [31] | Nutrient status and growth; colonization; immune effects | Observational case study; DB RCT | I | I | I | PP | Although 17 participants initially enrolled, only in a later description was it stated parents or children chose between identical packets (Cunningham-Rundles et al [31]). Of these, 14 were evaluable and 5 received placebo packets. |
| d′Ettorre, et al [43] | Inflammation and translocation | Observational | N/A | N/A | N/A | N/A | Comparator arm was 11 HIV-negative individuals given the 1 g probiotics bid. Bloodwork was done in each group (but not CD4 counts in the HIV- group). |
| Falasca, et al [40] | Inflammation and translocation | Observational | N/A | N/A | N/A | N/A | No comparator arm. 30 HIV+ men on ARV. |
| Gautam et al [23] | CD4, pediatric | RCT | A | I | I | PP | Randomization by using colored cards in white envelopes. Not blinded; participants received probiotic, MN syrup or sachets. |
| Gonzalez-Hernandez et al [3] | Safety, CD4, translocation | DB RCT | U | U | A | ITT | Explicit commentary on randomization and blinding methods lacking; analysis appeared to be ITT but not explicitly stated. The placebo was a product of Biogel without probiotics or prebiotic, but with the same flavor and characteristics. |
| Gori et al [18] | Soluble (s)CD14, LPS; effect on bacterial load in feces | DB RCT | U | A | A | ITT, PP | “Subjects were randomized in three groups …” but no further description. There may be conflicts of interest. Safety monitoring is not described. |
| Heiser et al [30] | Diarrhea from protease inhibitors | Randomized, not blinded | U | I | I | PP | Randomization not described; unblinded study (observational/pilot study). Glutamine added at week 4 only for treated group. |
| Hemsworth et al [41] | Immune status, bowel health, QoL | DB RCT, crossover | A | A | A | ITT, model | One dropped out within the first month. |
| Hummelen et al [46] | Bacterial vaginosis | DB RCT | A | A | A | ITT | Possible conflict of interest. |
| Hummelen et al [29] | CD4 | DB RCT | A | A | A | PP | Dr. Reid no longer holds patents for the use of Lactobacillus GR-1 and RC-14. Chr Hansen provided capsules; financial support from Danone Institute Canada, AFMnet. |
| Hummelen et al [36] | CD4 | DB RCT | A | A | A | ITT | It appears 3 early withdrawals were treated as data carried forward. |
| Irvine et al [21] | GI health, QoL, immune function. | Observational, retrospective | N/A | N/A | N/A | N/A | Observational. |
| Kerac et al [24] | Primary outcome was nutritional cure | DB RCT | A | A | A | ITT | 33-day study. No sepsis seen but investigated. Cure as weight-for-height >80% of National Center for Health Statistics median on 2 consecutive outpatient visits. |
| Saint-Marc et al [20] | Diarrhea; weight | Observational | N/A | N/A | N/A | N/A | Preliminary observational study. |
| Saint-Marc et al [33] | Diarrhea | DB RCT | A | A | A | ITT | One patient was precluded from taking doses due to a cerebral toxo-induced coma. |
| Salminen et al [35] | Primary GI symptoms, diarrhea. | DB RCT crossover | A | I | U | PP | This study was financially supported by Valio Ltd., Helsinki, Finland. 14-day washout period between treatment periods. |
| Schunter et al [42] | Translocation; cellular activation | DB RCT | A | A | A | PP | No adverse events or side effects reported or mentioned. |
| Trois et al [34] | Diarrhea; CD4 | DB RCT | U | A | U | ITT | Randomization by “cast lots” and products “blinded by a person” not involved in the study. |
| Villar-García et al [26] | Translocation | DB RCT | A | A | A | ITT, PP | 12 wk of trial with a subsequent 12-week follow-up. Computer-generated list; all blinded. IL-6 unaffected in ITT analysis but reduced in per protocol analysis. |
| Wolf et al [37] | Safety and tolerability | DB RCT | A | A | A | PP | Baseline information incomplete. Investigator could determine who received probiotics: less fecal odor, better consistency was observed. Packets were processed and coded (to maintain a double mask) by Anderson Packaging (Rockford, IL) |
| Yang et al [39] | Residual gut inflammation | DB RCT | I | I | A | PP | Randomization not described. Allocation not described nor was the placebo described. There may be conflicts of interest. |
Abbreviations: A, adequate; DB CT, double-blind controlled trial; DB RCT, DB randomized CT; GI, gastrointestinal; HIV, human immunodeficiency virus; I, inadequate; IL, interleukin; ITT, intent to treat; LPS, lipopolysaccharide; MN, micronutrient; N/A, not applicable; PP, per protocol; QoL, quality of life; U, unclear.
a Selection bias indicates how interventions were allocated and the randomization process used; performance bias describes the method used to conceal interventions/placebos; and detection bias assesses whether the provider, participant, or outcome assessor could distinguish intervention from comparator.