Table 5.
Summary of statistical findings of HAC with PD responses
| Study | N | Characteristics of PD responses measure | HAC characteristics | Statistical method | Result a |
|---|---|---|---|---|---|
| VL | |||||
| Baxi et al., 2015 | 271 | 271 VL[median(range)]: 5300 (80–4800000) copies/ mL VS: VL<80 copies/mL; VF: VL≥80 copies/mL |
HAC of NVP was categorized into four quintile: Q1 (0.25–16.28 ng/mg), Q2 (16.29–32.13 ng/mg), Q3 (32.14–57.33 ng/mg), Q4 (>57.33 ng/mg ) | Regression analysis | The ORA of VS increased with increasing quartile of HAC of NVP. ORA 2.47, 95% CI (1.09–5.6), p=0.031for Q2, ORA 3.33, 95% CI (1.33–8.3), p=0.010 for Q3, and ORA 9.17, 95% CI (3.2–26), p < 0.0001 for Q4 |
| Bernard et al., 1998 | 30 | VS: VL<200 copies/mL, n=19; VF: VL≥200 copies/mL, n=11 |
HAC of IDV [M±SD]: 17.85±5.08 μg/g for VS and 8.01 ±5.39 μg/g for VF | Mann-Whitney U test | p=0.0001 (test statistic: N/R) |
| Bernard et al., 2002 | 89 | VS:VL<500 copies/mL, n=65; VF: VL≥500 copies/mL, n=24 |
HAC of IDV [M±SD]: 24.4 ±16.0 μg/g for VS and 12.9 ±8.6 μg/g for VF | Student t test Mann-Whitney U test |
p<0.001 for the first 2-cm hair; p=0.016 for the second 2-cm hair; all p>0.05 for the third and fourth 2-cm hair |
| Chawana et al., 2017 | 42 | VS: VL <1000 copies/mL, n=18; VF : VL≥1000 copies/mL, n=24 |
HAC of ATV [median(IQR)]: 3.21 (2.35–6.61) ng/mg for VS, 0.94 (0.16–2.73) ng/mg for VF | Chi-square and Student t tests | p <0.0001 (test statistic: N/R) |
| Cohan et al., 2015 | 389 | VL[median(IQR)]: 4.3 (3.5–4.8) log10 copies/mL for EFV arm, and 4.1 (3.3–4.7) log10 copies/mL for LPV/RTV arm; and 4.1 (3.3–4.7) log10 copies/mL for LPV/RTV arm; VS: VL < 400 copies/mL | HAC of EFV, LPV and RTV: N/R | Not specified | OR 2.25 95% CI (1.53–3.30), p<0.001 |
| Duval et al., 2007 | 43 | VS:VL<50 copies/mL, n=29; VF: VL≥50 copies/mL, n=14 |
HAC of IDV[median(IQR)]: 15 (6–21) μg/g for VS and 8 (4–11) μg/g for VF | Regression analysis | ORA= 3.88, 95% CI (1.01–14.94), p=0.04 |
| Gandhi et al., 2009 224 | 224 | VL[median(IQR)]: 4.18 (1.90–6.49) log10 copies/mL for LPV/RTV arm, and 3.96
(1.90–6.10) log10 copies/mL for ATV/RTV arm; VS: VL<80 copies/mL, n=52 and 122 for LPV and ATV; VF: VL>80 copies/mL, n=18 and 32 for LPV and ATV |
HAC of LPV and ATV[median]: 1.58 ng/mg for VS and 0.29 ng/mg for VF in LPV arm; 2.60 ng/mg for VS and 0.67 ng/mg for VF in LPV arm; HAC of LPV and ATV was categorized into three tertiles: lowest(≤0.41 for LPV and ≤1.19 for ATV), middle (0.41–1.86 for LPV and 1.19–3.43 for ATV) and highest (>1.86 for LPV and >3.43 for ATV) | Wilcoxon rank test Regression analysis |
p =0.0008 for LPV, p <0.0001 for ATV,
p <0.0005 for RTV/LPV, p<0.0017 for RTV/ATV (test statistic:
N/R) The ORA of VS increased with increasing tertile of HAC of LPV and ATV. LPV arm: ORA 2.6, 95% CI (0.59–11.9), p=0.21 for middle tertile, ORA 39.8, 95% CI (0.59–11.9), p=0.006 for highest tertile; ATV arm: ORA 2.7, 95% CI (1.00–7.3), p=0.21 for middle tertile, ORA 7.7, 95% CI (2.0–29.7), p=0.003 for highest tertile |
| Gandhi et al., 2011 | 424 | VL[median(range)]: 5950 (80–2500000) copies/mL VS: VL<80 copies/mL |
HAC of ATV was categorized into five quintile: Q1 (0.05–0.658 ng/mg), Q2 (>0.658–1.78 ng/mg), Q3 (>1.78–3.13 ng/mg), Q4 (>3.13–5.19 ng/mg), Q5 (>5.19 ng/mg) | Regression analysis | The ORA of VS increased with increasing tertile of HAC of ATV. ORA 4.3, 95% CI (2.5–7.4) for Q2, ORA 12.7, 95% CI (7.1–22.8) for Q3, ORA 22.9, 95% CI (12.2–43.1) for Q4, ORA 59.8, 95% CI (29.0–123.2) for Q5, all p <0.001 |
| Gandhi et al. 2018 | 559 | VF: VL>1000 copies/ mL at or after 16 weeks and before 24 weeks, VL>200 copies/ mL at or after 24 weeks | HAC of ATV, DRV, and RAL [median (range)]: 3.52 (0.05–17.3), 2.71 (0.028–21), and
0.54 (0.02–4.2) ng/mg. HAC of ATV, DRV, and RAL was categorized into lowest, middle and highest tertiles: N/R |
The HR of VF increased with decreasing tertile of HAC of ATV, DRV, and RAL. HR 2.43 95% CI (1.96–3.13), p <0.001 for baseline HR for highest tertile, HR 1.71 95% CI (0.52–6.53), p = 0.39 for middle tertile, HR 6.79 95% CI (2.65–23.00), p = 0.004 for lowest tertile for follow-up |
|
| Koss et al., 2015 | 325 | VS: VL<400 copies/ mL, In EFV arm: 98.0% VS for delivery and 92.5% VS for 24 weeks postpartum In EFV arm: 87.4% VS for delivery and 90.6% VS for 24 weeks postpartum |
HAC of EFV and LPV [M (range)]: 5.7 (0.05–36.7) ng/mg and 6.6 (0.05–47.2) ng/mg for delivery; 6.3 (0.05–42) ng/mg and 5.7 (0.05–23.8) ng/mg for postpartum | Regression analysis |
OR 1.86, 95% CI (1.14–3.1), p=0.013 and
ORA 1.86, 95% CI (1.14–3.1), p=0.013 for
delivery; OR 1.58, 95% CI (1.18–2.1), p=0.002 and
ORA 1.81, 95% CI (1.22–2.7), p=0.003 for
postpartum LPV arm:OR 1.62, 95% CI (1.19–2.2), p=0.002 and ORA 1.90, 95% CI (1.33–2.7), p=0.0004 for delivery; OR=1.51, 95% CI (1.05–2.2), p=0.027 and adjusted ORA 1.53, 95% CI (1.05–2.2), p=0.026 for postpartum |
| Pintye et al., 2017 | 244 | VL[median(IQR)]: 5.0 (4.3–5.6) log10 copies/mL VS: VL<400 copies/ mL or VL<1000 copies/ mL, VF: VL>400 copies/mL or VL>1000 copies/mL |
HAC of LPV[median(IQR)]: 9.66 (7.00–13.11) ng/mg | Regression analysis | OR 0.56, 95% CI (0.47–0.67), p<0.001 and ORA 0.41, 95% CI (0.29–0.58), p<0.001 for VL>400 copies/mL; OR 0.54, 95% CI (0.45–0.65), p<0.001 and ORA 0.46, 95% CI (0.34–0.63), p<0.001 for VL>1000 copies/mL |
| Prasitsuebsai et al., 2015 | 149 | VS: VL<1000 copies/ mL, n=132 VF: VL>1000 copies/mL, n=17 VS: VL<50 copies/ mL, n=104 |
HAC of LPV [median(IQR)]: 9.96 (0.51–12.31) ng/mg for VS, 5.43(3.21–9.01) ng/mg
for VF; HAC of LPV was categorized into four quintile: Q1 (≤6.11ng/mg), Q2 (6.36–9.56 ng/mg), Q3 (9.75–12.13 ng/mg), Q4 (12.15–22.10 ng/mg) HAC of EFV [median (range)]: Cape Mixed Ancestry: 5.9 (0.9–20.9) ng/mg for VS and 5.5 (1.2–10.2) ng/mg for VF; South African Blank: 5.2 (0.5–27.0) for VS and 8.2 (1.1–9.9) for VF. |
Wilcoxon rank test; Regression analysis Regression analysis |
p = 0.003 (test statistic: N/R); The OR of VS increased with increasing quartile of HAC of LPV. ORA 4.05, 95% CI (1.01–16.15) for Q2, ORA 6.25, 95% CI (1.27–30.88) for Q3 and Q4, p =0.02 |
| Röhrich et al., 2016 | 120 | VF: VL>50 copies/mL, n=16 | Regression analysis | Not association (test statistic: N/R; significance N/R) | |
| Servais et al., 2001 | 5 | VL: N/R | HAC of IDV: N/R | Not specified | P < 0.001 (test statistic: N/R) |
| Tabb et al., 2018 | 227 | VS: VL<400 copies/mL, n=50, 53, 5, 28, and 33 for NVP, EFV, ATV, LPV and RTV,
respectively; VF: VL>400 copies/mL, n=28, 33, 8, 22, and 33 for NVP, EFV, ATV, LPV and RTV, respectively |
HAC of NVP, EFV, ATV, LPV and RTV [median (IQR)]: 4.85 (3.11–8.47), 54.85 (41.90–75.30), 7.09 (2.30–7.12), 9.72 (6.32–16.10), and 0.84 (0.61–1.27) ng/mg for VS, respectively; 0.98 (0.24–3.65), 34.35 (13.55–59.80), 2.06 (0.75–3.22), 0.53 (0.23–1.42), and 0.14 (0.03–0.51) ng/mg for VF, respectively | Wilcoxon rank test | All p < 0.001 for NVP, EFV, LPV, and
RTV; p =0.11 for ATV (test statistic: N/R) |
| van Zyl et al., 2011 | 93 | VS: VL<400 copies/mL, n=19 and 19 for LPV and RTV; VF: VL>400 copies/mL, n=19 and 19 for LPV and RTV |
HAC of LPV and RTV [median (IQR)]: 8.36 (5.63–12.13) and 0.81 (0.46–1.22) ng/mg for VS; 0.97 (0.27–3.15) and 0.13 (0.04–0.54) ng/mg for VF | Wilcoxon rank test | p =0.0009 for LPV; p =0.0084 for RTV (test statistic: N/R |
| Yan et al., 2016 | 287 | VS: VL<1000 copies/mL, n=208; VF: VL>400 copies/mL, n=39 for VF without drug resistance and n=40 for VF with drug resistance |
HAC of 3TC[M±SD]: 915.0±670.5 ng/g for VS, 284.1±538.9 ng/g for VF without drug resistance, and 648.4±616.9 ng/g for VF with drug resistance | Wilcoxon rank test | p < 0.001 for compare VS with VF without drug resistance; p=0.0125 for compare VS with VF with drug resistance (test statistic: N/R) |
| Renal toxicity | |||||
| Baxi et al., 2015 | 88 | Creatinine clearance [M±SD]: 111±28.3 mL/min for daily dosing, 107±32.4 mL/min for intermittent dosing | HAC of TFV and FTC: N/R | Regression analysis | OR 1.02 95% CI (0.89–1.16) for TFV and OR 1.03 95% CI (0.91–1.17) for FTC, all p>0.0 |
| Baxi et al., 2018 | 47 | Creatinine clearance [median (IQR)]: 122 (97–144) mL/min | HAC of TFV: N/R | Regression analysis | OR −6% 95% CI (−12%−1%), p= 0.08; ORA =−6% 95% CI (−12%−1%), p= 0.75 |
| Gandhi et al. 2016 | 220 | Creatinine clearance [median (IQR)]: 112 (99–128) mL/min | HAV of TFV and FTC [M ± SD]:0.027 ± 0.065 ng/mg and 0.45 ± 0.73 ng/mg | Mix effects models | p=0.008 for TFV; p=0.006 for FTC (test statistic: N/R) |
| Gandhi et al. 2017 | 280 | Creatinine clearance [median (IQR)]: 129 (109–147) mL/min | HAC of TFV: N/R | Mix effects models | p=0.011 (test statistic: N/R) |
| Liu et al., 2014 | 23 | Creatinine clearance [M±SD]: 129.4±31.1 mL/min | HAC of TFV: N/R | Regression analysis | p=0.52 (test statistic: N/R) |
| Seifert et al. 2018 | 45 | Creatinine clearance [M ± SD]: 119±36 mL/min for old adult, 96±32 mL/min for young adult | HAC of TFV: N/R | Regression analysis | OR 16.9% 95% CI (9.1%−25.3%), p= 0.0001; ORA 15.9% 95% CI (7.4%−25.0%), p= 0.0006 |
Notes.
*
p<0.05
**
p<0.01
***
p<0.001
HAC=hair ARV concentration; PD=pharmacodynamics; N/R=not reported; VL=viral load; VS=virologic suppression; VF=virologic failure; 3TC=Lamivudine; TFV=Tenofovir; FTC=Emtricitabine; EFV=Efavirenz; NVP=Nevirapine; IDV=Indinavir; LPV=Lopinavir; RTV=Ritonavir; ATV=Atazanavir; DRV=Darunavir; RAL=Raltegravir; OR=odds ratios; HR=Hazard ratios; M=mean; SD=standard deviation; IQR=interquartile range.
a
Odds ratios, hazard ratios, and relative risks are unadjusted unless denoted by subscript “A”.