Table 2.
Distribution of Clinical Factors and C24 Antiretroviral Drug Concentrations by Female Genital Tract Microbiome Community Type Over the Menstrual Cycle in 20 Human Immunodeficiency Virus–Infected Womena
| Variable | Total Cohort (N = 109 Visits)a |
Microbiome Community Type | ||
|---|---|---|---|---|
| Low Diversity (n = 40 Visits) |
Intermediate Diversity (n = 28 Visits) |
High Diversity (n = 41 Visits) |
||
| Nugent score, median (Q1, Q3)b | 7 (4, 9) | 3 (1, 5) | 7 (5, 8) | 9 (8, 10) |
| Bacterial vaginosis, Nugent score ≥7, No. (%)c | 56 (57) | 3 (9.1) | 19 (67.9) | 34 (91.9) |
| Age, y, median (Q1, Q3) | 38 (33, 41) | 37 (36, 43) | 35 (39, 36) | 40 (30, 41) |
| BMI, kg/m2, median (Q1, Q3)* | 27 (25, 37) | 26 (26, 37) | 37 (35, 41) | 27 (23, 32) |
| Antibiotic for vaginal infection within 30 days of screening, No. (%)c | 29 (26.6) | 14 (35) | 3 (10.7) | 12 (29.3) |
| Recent sexual activity, No. (%) | 47 (43.1) | 17 (42.5) | 11 (39.3) | 20 (48.8) |
| FGT semen contamination, No. (%) | 8 (7.3) | 0 (0) | 5 (17.9) | 3 (7.3) |
| FGT leukocytes >125 cells/μL, No. (%) | 30 (27.5) | 10 (25) | 11 (39.3) | 9 (22) |
| FGT RBCs >25 cells/μL, No. (%) | 62 (57.4) | 18 (45) | 15 (53.6) | 13 (32.5) |
| Menstrual cycle characteristics, No. (%) | ||||
| Nonovulatory phase | 31 (28.4) | 10 (25) | 10 (35.7) | 11 (26.8) |
| Ovulatory phase | 78 (71.6) | 30 (75) | 18 (64.3) | 30 (73.2) |
| Follicular, No. (%) of ovulatory | 39 (50) | 15 (50) | 8 (44.4) | 16 (53.3) |
| Luteal, No. (%) of ovulatory | 39 (50) | 15 (50) | 10 (55.6) | 14 (46.7) |
| Plasma hormone concentrations, pg/mL, median (Q1, Q3) | ||||
| Estradiol (n = 108) | 27.01 (6.24, 58.5) | 27.14 (3.58, 61.15) | 35.96 (12.98, 63.15) | 24.88 (0.00, 51.10) |
| Progesterone (n = 109) | 0.58 (0.31, 4.64) | 0.59 (0.29, 4.04) | 0.54 (0.3, 4.68) | 0.70 (0.38, 5.03) |
| FGT antiretroviral concentrations, ng/mL, median C24 (Q1, Q3)d | ||||
| ATV | 1435 (705, 2655) | 1200 (705, 2510) | 1818 (1048, 47778) | 1435 (541, 2330) |
| TFV | 215 (117, 473) | 157 (100, 251) | 560 (141, 1272) | 202 (90, 343) |
| FTC | 1252 (495, 1840) | 1252 (431, 1780) | 1133 (640, 2678) | 1284 (455, 1670) |
| Plasma antiretroviral concentration, ng/mL, median C24 (Q1, Q3) | ||||
| ATV | 620 (380, 957) | 612 (400, 880) | 612 (407, 915) | 666 (346, 1390) |
| TFV | 74 (44, 104) | 89 (63, 120) | 55 (40, 88) | 76 (35, 101) |
| FTC | 69 (46, 131) | 98 (54, 152) | 55 (40, 88) | 64 (43, 135) |
| FGT:plasma antiretroviral concentration, median (Q1, Q3) | ||||
| ATV | 2.29 (1.17, 5.30) | 2.18 (1.20, 4.65) | 4.42 (1.76, 8.16) | 1.52 (0.86, 3.67) |
| TFV | 3.22 (1.27, 8.62) | 2.03 (0.71, 4.42) | 10.80 (4.92, 20.59) | 2.73 (1.69, 6.14) |
| FTC | 13.36 (7.34, 24.75) | 11.36 (3.36, 17.84) | 20.06 (11.73, 38.26) | 13.10 (7.89, 23.26) |
Abbreviations: ATV, atazanavir; BMI, body mass index; C24, antiretroviral drug concentration measured 24 hours after last dose; FGT, female genital tract; FTC, emtricitabine; Q1, quartile 1; Q3, quartile 3; RBC, red blood cell; SD, standard deviation; TFV, tenofovir.
aSamples collected from 20 participants during 109 study visits unless N for the individual variable is otherwise specified. Study visits were completed in a single menstrual cycle for 16 participants or were completed outside the cycle window because of early menses prior to completion of study visits (4 participants, 5 [4.6%] study visits). Trough FGT antiretroviral concentrations were obtained, with the median time from last antiretroviral drug doses to FGT sampling 24 (Q1, Q3: 23, 25) hours, though 9 (8.3%) sets of samples were collected >4 hours from a true 24-hour trough. Plasma sampling occurred a median of 24 (Q1, Q3: 22, 24) hours from last antiretroviral drug doses and within an hour of FGT sampling for 82 (75.2%) of visits and not more than 1 hour from genital sampling in the remaining visits (27 visits [24.8%]).
bParticipant visits with Gram stain and Nugent scores available, n = 98 (low-diversity microbiome community type [mCT], n = 33; intermediate-diversity mCT, n = 28; high-diversity mCT, n = 37).
cMetronidazole alone or in combination with another oral antibiotic(s). Among the 5 participants with antibiotic use within 30 days of screening, the mCT at the time of the first study visit was of low diversity (n = 3), intermediate diversity (n = 0), and high-diversity (n = 2).
dFGT antiretroviral concentrations available for 107 visits (n = 2 missing from 2 study visits by 1 participant, both visits with high-diversity mCT identified).
*Denotes variable with a statistically significant (P < .05) association with mCT in pairwise bivariate mixed models identified. Odds ratios per unit increase in BMI (kg/m2) for high- vs intermediate-diversity mCT, 0.68 (95% confidence interval [CI], .5–.94]; P = .0191), for low- vs intermediate-diversity mCT, 0.87 [.72–1.04]; P = .1145), and for low- vs high-diversity mCT, 1.16 [.85–1.58]; P = .3370). We were unable to estimate associations between semen contamination and low-diversity mCTs as no low-diversity visits with semen contamination were present. Other bivariate associations among those tested each had P > .05.