Clinical predictor score to identify patients at risk of poor viral load suppression at six months on antiretroviral therapy: results from a prospective cohort study in Johannesburg, South Africa

Figures & data

Table 1 Summary of data sources and study variables

	Source
Parameter	Therapy Edge-HIV™	Prospective study
Eligibility criteria	According to NDOH guidelines	≥18+ not pregnant and not transferred in
Demographic characteristics	Age, gender, national ID number, TE number, nationality, employment status	Age, gender, national ID number, TE number, nationality, employment status
ART regimen	According to NDOH guidelines; TDF/3TC or EMT/EFV or NVP; d4T/3TC/EFV or NVP	According to NDOH guidelines; TDF/3TC or EMT/EFV or NVP; d4T/3TC/EFV or NVP
Medical visit	1, 3, 6 months and every 6 months thereafter	0, 6, 12, 24 months after ART initiation
Laboratory tests	According to NDOH guidelines; CD4, VL (6 and 12 months), full blood count (eg, hemoglobin, hematocrit, MCV) and serum creatinine. WHO stage at ART initiation	Additional lab tests included: (i) viral load at ART initiation (ii) albumin, full blood count, total lymphocyte count, MCV, serum lactate at 0, 6, 12, 24 months WHO stage assessed at 6, 12, 24 months
Procedures	As clinically indicated	Self-reported adherence (eg VAS, PIT, SMAQ) Body composition changes using bioelectrical impedance

Abbreviations: MCV, mean cell volume; TLC, total lymphocyte count; ART, antiretroviral therapy; NDOH, National Department of Health; SMAQ, Simplified Medication Adherence Questionnaire; PIT, pill Identification test; TDF, tenofovir; 3TC, lamivudine; EMT, emtricitabine; EFV, efavirenz; NVP, nevirapine; d4T, stavudine; VL, viral load; ID, identification; TE, TherapyEdge-HIV; VL, viral load; WHO, World Health Organization; VAS, visual analog scale.

Figure 1 Flowchart of the study participant in the LCM cohort study.

Abbreviations: LCM, low cost monitoring; ART antiretroviral therapy.

Table 2 Baseline demographic and clinical characteristics of 296 ART-naive patients, stratified by a viral load at 6 months on ART

Viral load (copies/mL) at 6 months on ART
Variables	VL ≥400 (n=72)	VL <400 (n=167)	No viral load (n=57)
Age
≤35 years old	27 (37.5%)	69 (41.3%)	22 (61.4%)
>35 years old	45 (62.5%)	98 (58.7%)	35 (39.6%)
Sex
Male	30 (41.7%)	53 (32.0%)	17 (29.8%)
Female	42 (58.3%)	114 (68.0%)	40 (70.2%)
Education
Beyond secondary school	7 (8.2%)	5 (2.4%)	5 (8.7%)
Secondary school	47 (67.1%)	120 (73.0%)	41 (71.9%)
Primary school	7 (9.6%)	13 (8.0%)	2 (3.5%)
Illiterate/not yet schooled	4 (6.8%)	6 (4.3%)	6 (10.5%)
Unknown	6 (8.2%)	19 (12.3%)	3 (5.2%)
Employed
No	28 (38.9%)	66 (39.5%)	24 (42.0%)
Yes	44 (61.1%)	101 (60.5%)	33 (58.0%)
Nationality
South African	64 (90.1%)	139 (83.2%)	50 (87.1%)
Non-South African	7 (9.9%)	28 (16.7%)	7 (12.9%)
ART regimen at initiation
TDF-based regimen	61 (84.7%)	145 (86.8%)	50 (87.7%)
d4T-based regimen	10 (13.9%)	19 (11.4%)	5 (8.7%)
Other first-line regimen	1 (1.4%)	3 (1.8%)	2 (3.6%)
WHO stage
I/II	62 (86.1%)	144 (87.0%)	54 (94.6%)
III/IV	10 (13.9%)	23 (13.0%)	3 (5.4%)
CD4 count (cells/mm^3)
<50	11 (15.2%)	17 (10.1%)	9 (16.3%)
51–100	12 (16.6%)	21 (12.5%)	5 (7.2%)
101–200	17 (23.6%)	41 (24.5%)	14 (25.4%)
201–350	26 (36.1%)	73 (43.7%)	22 (40.0%)
>350	6 (8.3%)	15 (9.9%)	7 (10.9%)
Body mass index (kg/m^2)
Median (IQR)	23.6 (20.1–26.2)	23.9 (21.1. – 28.3)	23.4 (21.4–28.5)
BMI categories
<18.5	2 (4.2%)	4 (3.7%)	1 (3.1%)
18.5–24.9	28 (58.3%)	44 (40.0%)	19 (59.4%)
25–29.9	11 (22.9%)	33 (30.0%)	9 (28.1%)
>30	7 (14.6%)	29 (26.4%)	3 (9.4%)
Hemoglobin (g/dL): median (IQR)	11.95 (10.1–13.5)	12.5 (11–13.5)	11.9 (12.1–13.4)

Abbreviations: TDF, tenofovir; 3TC, lamivudine; EMT, emtricitabine; EFV, efavirenz; NVP, nevirapine; d4T, stavudine; BMI, body mass index; VL, viral load; IQR, interquartile range; WHO, World Health Organization, ART, antiretroviral therapy.

Table 3 Sensitivity and specificity of self-reported adherence at 6 months on ART compared to viral load as “gold standard”

	VL ≥400 (n=49)	VL <400 (n=114)	Se (95% CI)	Sp (95% CI)	PPV (95% CI)	NPV (95% CI)	ROC curve C-statistic
VAS <90%
Non-adherent	12 (24.5%)	14 (12.3%)
Adherent	37 (75.5%)	100 (87.7%)	24.5% (17.89–31.9)	87.7% (82.61–92.76)	46.2% (38.57–53.81)	72.9% (66.18–79.81	0.558
Multi-method
Non-adherent	9 (18.3%)	15 (13.2%)
Adherent	40 (81.6%)	99 (86.8%)	18.4% (9.2–32.5)	86.8% (78.9–92.2)	37.5% (19.6–59.2)	71.2% (62.8–78.4)	0.539
SMAQ
Non-adherent	13 (26.5%)	24 (21.0%)
Adherent	36 (73.5%)	90 (79.0%)	26.5% (15.4–41.3)	78.9% (70.1–85.8)	35.1% (20.7–52.6)	71.4% (62.6–78.9)	0.524

Abbreviations: VL, viral load; CI, confidence interval; Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value; ROC, receiver operating characteristics curve; VAS, visual analog scale; SMAQ, Simplified Medication Adherence Questionnaire.

Table 4 Crude and adjusted predictors of poor virologic suppression at 6 months after ART initiation, using Modified Poisson regression (n=163)

	HIV/RNA viral load ≥400 copies/mL
Baseline characteristics	Crude RR (95% CI)	aRR (95% CI)	Score^a
Age
≤35 years old	Reference		0
>35 years old	1.11 (0.74–1.77)	1.07 (0.67–1.73)	+1
Sex
Female	Reference		0
Male	1.34 (0.91–1.97)	1.46 (0.93–2.29)	+1
Level of education
Beyond secondary school	2.50 (1.05–5.92)
Secondary school	1.17 (0.65–4.57)
Primary school	1.45 (0.58–3.66)
Illiterate/not yet schooled	1.73 (0.65–4.57)
Unknown	Reference
Unemployment
Yes	1.01 (0.68–1.51)
No	Reference
Nationality
South African	1.57 (0.78–3.15)
Non-South African	Reference
ART regimen initiation
TDF-based regimen	0.72 (0.12–4.27)
d4T-based regimen	0.85 (0.49–1.48)
Other first-line regimens	Reference
WHO stage at ART initiation
I/II	Reference		0
III/IV	1.32 (0.44–3.95)	1.10 (0.83–1.17)	+1
CD4 count at ART initiation
<200	Reference
200–350	0.85 (0.50–1.10)
≥350	0.80 (0.30–0.40)
Six months on ART/change from baseline to 6 months on ART
BMI <18.5 kg/m^2
Yes	1.10 (0.34–3.51)
No	Reference
BMI drop from baseline >2.5 kg/m^2
Yes	0.91 (0.56–1.48)
No	Reference
Hemoglobin drop from baseline ≥1 g/dL
Yes	0.58 (0.16–2.11)
No	Reference
Failing to increase CD4 count by ≥50 cells/mm^3
Yes	0.90 (0.47–1.71)
No	Reference
Absolute lymphocyte count <2000 cells/µL
Yes	0.63 (0.37–1.13)
No	Reference
Platelet count <150 cells/mm^3
Yes	2.24 (0.98–5.13)	2.73 (1.02–6.92)*	+3
No	Reference		0
Absolute MCV change <14.5 fL
Yes	0.94 (0.64–1.39)	1.32 (0.58–2.95)	+1
No	Reference		0
Albumin unchanged after 6 months
Yes	0.98 (0.57–1.70)
No	Reference
MCH <2.7 fmol/cell after 6 months
Yes	0.31 (0.04–2.08)
No	Reference
Missing at least two ARV by ≥7 days
Yes	1.68 (0.79–3.85)	2.35 (1.08–5.11)*	+2
No	Reference		0
VAS score test <90%
Yes	1.70 (1.03–2.81)	1.65 (1.01–2.71)*	+2
No	Reference		0
Multi-method approach
Yes	1.30 (0.72–2.32)
No	Reference
SMAQ
Yes	1.22 (0.73–2.06)
No	Reference
Serum lactate ≤2 mmol/L
Yes	1.07 (0.72–1.57)
No	Reference

^aThe score calculated as the sum of the adjusted relative risks divided by the smallest regression coefficient and the result multiplied by 10 for each predictor rounded to the nearest integer. Other first-line regimens: ZDV-EFV-3TC or TDF-3TC-AZT. *Significant at the 0.05 level.

Abbreviations: RR, relative risk; aRR, adjusted relative risk; ARV, antiretroviral; TDF, tenofovir fumarate; d4T, stavudine. BMI, body mass index; MCV, mean cell volume; MCH, mean corpuscular hemoglobin; SMAQ, Simplified Medication Adherence Questionnaire; ART, antiretroviral therapy; WHO, World Health Organization; VAS, visual analog scale.

Table 5 Diagnostic accuracy of the clinical prediction pcore (CPS) at different cutoff points at 6 months after ART initiation

Diagnostic risk score	VL ≥400 (n=72)	VL <400 (n=167)	Se	Sp	PPV	NPV
Predicted probability ≥2	70 (30.2%)	162 (69.8%)	97.2%	3.0%	30.2%	71.4%
Predicted probability <2	2 (28.6%)	5 (71.4%)
Predicted probability ≥3	64 (30.3%)	147 (69.7%)	88.9%	12.0%	30.3%	71.4%
Predicted probability <3	8 (28.6%)	20 (71.4%)
Predicted probability ≥4	57 (32.9%)	116 (67.1%)	79.2%	30.5%	33.0%	77.3%
Predicted probability <4	15 (22.7%)	51 (77.3%)
Predicted probability ≥5	47 (34.6%)	89 (65.4%)	65.3%	46.7%	34.6%	75.7%
Predicted probability <5	25 (24.3%)	78 (75.7%)

Abbreviations: SMAQ, Simplified Medication Adherence Questionnaire; Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value; VL, viral load.

Figure 2 Diagnostic accuracy of the algorithm compared to viral load as “the gold standard”.

Abbreviations: ART, antiretroviral therapy; ARV, antiretroviral; MCV, mean cell volume; VAS, visual analog scale; WHO, World Health Organization.