Alcohol, Smoking, Recreational Drug Use and Association With Virological Outcomes Among People Living With HIV

Cross-Sectional and Longitudinal Analyses

Timothy P. W. Jones; Fiona C. Lampe; Alejandro Arenas-Pinto; Colette Smith; Jeff McDonnell; Lewis Haddow; Margaret Johnson; Elaney Yousef; Monica Lascar; Anna Maria Geretti; Lorraine Sherr; Simon Collins; Andrew N. Phillips; Alison J. Rodger

Disclosures

HIV Medicine. 2022;23(3):209-226.

Abstract and Introduction

Abstract

Objectives: There is increasing evidence to suggest that people living with HIV (PLWH) have significant morbidity from alcohol, recreational drug use and cigarette smoking. Our aim was to report associations of these factors with antiretroviral therapy (ART) non-adherence, viral non-suppression and subsequent viral rebound in PLWH.

Methods: The Antiretroviral Sexual Transmission Risk and Attitudes (ASTRA) study recruited PLWH attending eight outpatient clinics in England between February 2011 and December 2012. Data included self-reported excessive drinking (estimated consumption of > 20 units of alcohol/week), alcohol dependency (CAGE score ≥ 2 with current alcohol consumption), recreational drug use (including injection drug use in the past 3 months), and smoking status. Among participants established on ART, cross-sectional associations with ART non-adherence [missing ≥2 consecutive days of ART on ≥2 occasions in the past three months] and viral-non suppression [viral load (VL) > 50 copies/mL] were assessed using logistic regression. In participants from one centre, longitudinal associations with subsequent viral rebound (first VL > 200 copies/mL) in those on ART with VL ≤ 50 copies/mL at baseline were assessed using Cox regression during a 7-year follow-up.

Results: Among 3258 PLWH, 2248 (69.0%) were men who have sex with men, 373 (11.4%) were heterosexual men, and 637 (19.6%) were women. A CAGE score ≥ 2 was found in 568 (17.6%) participants, 325 (10.1%) drank > 20 units/week, 1011 (31.5%) currently smoked, 1242 (38.1%) used recreational drugs and 74 (2.3%) reported injection drug use. In each case, prevalence was much more common among men than among women. Among 2459 people on ART who started at least 6 months previously, a CAGE score ≥ 2, drinking > 20 units per week, current smoking, injection and non-injection drug use were all associated with ART non-adherence. After adjusting for demographic and socioeconomic factors, CAGE score ≥ 2 [adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.09–2.13], current smoking (aOR = 1.58, 95% CI: 1.10–2.17) and injection drug use (aOR = 2.11, 95% CI: 1.00–4.47) were associated with viral non-suppression. During follow-up of a subset of 592 people virally suppressed at recruitment, a CAGE score ≥ 2 [adjusted hazard ratio (aHR) = 1.66, 95% CI: 1.03–2.74], use of 3 or more non-injection drugs (aHR = 1.82, 95% CI: 1.12–3.57) and injection drug use (aHR = 2.73, 95% CI: 1.08–6.89) were associated with viral rebound.

Conclusions: Screening and treatment for alcohol, cigarette and drug use should be integrated into HIV outpatient clinics, while clinicians should be alert to the potential for poorer virological outcomes.

Introduction

Effective antiretroviral therapy (ART) and increased HIV testing have dramatically increased survival in people living with HIV (PLWH). However, lifestyle factors such as alcohol consumption, smoking and recreational drug use may have an impact on adherence to ART and HIV outcomes as well as increasing risk of non-HIV-related morbidity. Previous questionnaire studies have suggested that alcohol, smoking and recreational drug use are prevalent in PLWH.^[1–7]

The WHO attribute 5.9% of global deaths to alcohol consumption.^[8] There is evidence that alcohol intake may have a greater impact on the mortality and morbidity of PLWH compared with the general population, although the causes for this remain unclear.^[9] While there is evidence that higher alcohol consumption is associated with ART non-adherence among PLWH,^[1] the impact of alcohol on virological outcomes of ART per se is less clear. Although several studies reported a positive association between high alcohol intake and viral load rebound,^{[2,5,10–13]} others have not found significant associations.^[1,14,15] Lack of consistent definitions of what constitutes hazardous or harmful alcohol use, the potential for non-linear associations with amount of alcohol and, in some cases, small sample sizes have hampered interpretation of this literature.

Reduced adherence to ART and higher viral loads have likewise been associated with cigarette smoking^[16] and use of recreational drugs, including 'chemsex'.^[4] There is evidence that PLWH who smoke are particularly susceptible to lung damage from smoking, with those stable on treatment expected (based on modelling analysis) to lose more years to smoking than to HIV.^[17] Although people who inject drugs are known to have poor health outcomes, the effects of non-injected recreational drug use in PLWH is less clear, although recent studies suggest that this may also have a negative impact on adherence.^[3,18] In combination, these findings may indicate that adverse lifestyle factors have significant implications for increased morbidity in PLWH, as well as potential implications for HIV treatment outcomes and onward transmission in PLWH on ART.

Much of the literature has focused on PLWH already identified as high risk for alcohol and drug use disorders.^[19] Furthermore, few studies have reported on the use of drugs, alcohol, smoking and the association with virological outcomes among PLWH in the UK. Different societal views and practices make unselected country-specific data invaluable in measuring the impact of such lifestyle factors and in guiding the public health response. The aim of this study was to use data from the Antiretroviral Sexual Transmission Risk and Attitudes (ASTRA) study^[20] to report levels of alcohol, smoking and recreational drug use among PLWH in England, to assess associations with demographic socioeconomic, health and HIV-related factors, and to examine the associations with ART non-adherence, viral non-suppression and subsequent virological rebound over a 7-year period.

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Next Section

Abstract and Introduction
Methods
Results
Discussion
Summary
References

Table 1. Participant characteristics and associations with alcohol use and dependency, recreational drug use and cigarette smoking
Demographics	Participant cohort		Alcohol dependence: cage score ≥ 2 and current alcohol consumption					> 20 units alcohol/week from AUDIT					Recreational drug use (in the past 3 months)					Current smoker
Demographics	n = 3258	Column %	568/3258 (17.4%)	Column %	OR	95% CI	P-value	325/3258 (10.0%)	Column %	OR	95% CI	P-value	1242/3258 (38.1%)	Column %	OR	95% CI	P-value	1011/3258 (31.0%)	Column %	OR	95% CI	P-value
Male	2621/3258	80.4%	503/568	88.6%	1.45	1.09–1.93	0.0081	314/325	96.6%	7.57	4.10–13.98	< 0.0001	1198/1242	96.5%	11.30	8.13–15.83	< 0.0001	944/1011	93.4%	4.69	3.57–6.16	< 0.0001
Mean age (year) (SD)	45.2	(9.63)	44.3	(8.72)				46.4	(9.45)				43.7	(9.06)				44.0	(9.07)
Age > 50 years	971/3258	29.8	136/568	23.9%	0.70	0.57–0.87	0.0009	112/325	34.5%	1.27	1.00–1.63	0.0492	294/1242	23.7%	0.61	0.52–0.72	< 0.0001	253/1011	25.0%	0.71	0.60–0.84	0.0001
Median CD4 lymphocyte count (× 10⁹/mL) (IQR)	537	(390–721)	540	(580–736)				539	(392–729)				556	(418–757)				559	(402–763)
CD4 < 500 copies/mL	1388/3235	42.9%	323/568	56.9%	1.05	0.87–1.27	0.6023	189/325	58.2%	0.96	0.76–1.21	0.7384	487/1234	38.7%	0.76	0.66–0.88	0.0002	402/1011	40.0%	0.85	0.73–0.99	0.0397
Gender/sexual orientation
MSM	2248/3258	69.0%	435/568	76.6%	1		0.0180	282/325	86.8%	1		< 0.0001	1138/1242	91.6%	1		< 0.0001	829/1011	82.0%	1		< 0.0001
Heterosexual men	373/3258	11.4%	68/568	12.0%	1.16	0.87–1.56	—	32/325	9.9%	0.67	0.46–0.98	—	60/1242	4.8%	0.18	0.14–0.25	—	115/1011	11.4%	0.79	0.62–1.00	—
Women	637/3258	19.6%	65/568	11.4%	0.49	0.53–0.94	—	11/325	3.4%	0.12	0.07–0.23	—	44/1242	3.5%	0.07	0.05–0.10	—	67/1011	6.6%	0.21	0.16–0.27	—
Ethnic origin
White	2220/3185	69.7%	434/563	77.1%	1		0.1803	291/324	89.8%	1		< 0.0001	1073/1242	86.4%	1		< 0.0001	819/1011	81.0%	1		< 0.0001
Black African	614/3185	19.2%	84/563	14.9%	1.00	0.76–1.30	—	14/324	4.3%	0.16	0.09–0.28	—	21/1242	1.7%	0.04	0.02–0.06	—	55/1011	5.4%	0.17	0.13–0.23	—
Black other	125/3185	3.9%	18/563	3.2%	0.81	0.48–1.35	—	5/324	1.5%	0.29	0.12–0.71	—	45/1242	3.6%	0.60	0.41–0.88	—	48/1011	4.7%	1.13	0.77–1.64	—
All other	226/3185	7.1%	27/563	4.8%	0.65	0.42–0.99	—	14/324	4.3%	0.44	0.25–0.77	—	103/1242	8.3%	0.56	0.44–0.72	—	89/1011	8.8%	0.73	0.36–0.96	—
ART status
On ART	2771/3202	86.5%	466/564	82.6%	1		0.0297	269/322	83.5%	1		0.1636	1033/1234	83.7%	1	—	< 0.0001	837/1005	83.3%	1	—	0.0011
Stopped ART	65/3202	2.0%	13/564	2.3%	0.92	0.71–2.56	—	10/322	3.1%	2.26	0.85–3.34	—	20/1234	1.6%	0.75	0.44–1.27	—	23/1005	2.3%	0.75	0.39–2.10	—
Never on ART	366/3202	11.4%	85/564	15.1%	1.43	1.09–1.86	—	43/322	13.3%	1.61	0.89–1.76	—	103/1234	14.7%	1.65	1.32–2.05	—	145/1005	14.4%	1.52	1.21–1.90	—
Social support
Most (25)	1042/3258	32.0%	147/559	26.3%	1		0.0002	90/325	27.7%	1		0.0710	385/1236	31.1%	1		0.3891	288/999	28.8%	1		0.0003
Medium (15–24)	1534/3258	47.1%	287/559	51.3%	1.39	1.12–1.73	—	174/325	53.5%	1.36	1.04–1.78	—	591/1236	47.8%	1.07	0.91–1.26	—	485/999	48.5%	1.22	1.02–1.45	—
Least (5–14)	620/3258	19.0%	125/559	22.4%	1.73	1.31–2.26	—	61/325	18.8%	1.15	0.82–1.62	—	260/1236	21.0%	1.23	1.01–1.51	—	226/999	22.6%	1.52	1.22–1.87	—
Mental health symptoms
Depression (PHQ-9 score ≥ 10)	884/3258	27.1%	207/568	36.4%	1.92	1.57–2.35	< 0.0001	101/325	31.1%	1.24	0.96–1.59	0.0930	232/1242	18.7%	1.24	1.07–1.46	0.0060	244/1011	24.1%	1.80	1.53–2.12	< 0.0001
Anxiety (GAD-7 score ≥ 10)	715/3258	21.9%	172/568	30.3%	1.71	1.39–2.09	< 0.0001	86/325	26.5%	1.32	1.01–1.71	0.0382	272/1242	21.9%	1.00	0.84–1.18	0.9604	290/1011	28.7%	1.75	1.47–2.09	< 0.0001
Money for basic needs
Always	1392/3193	43.6%	254/564	45.0%	1		0.0265	165/324	50.9%	1		0.0153	600/1228	48.9%	1		< 0.0001	369/994	37.1%	1		< 0.0001
Sometimes or mostly	1401/3193	43.9%	224/564	39.7%	0.86	0.71–1.05	—	118/324	36.4%	0.69	0.54–0.89	—	502/1228	40.9%	0.74	0.63–0.86	—	474/994	47.7%	1.44	1.23–1.70	—
No	400/3193	12.5%	86/564	15.3%	1.25	1.32–2.35	—	41/324	12.7%	0.87	0.61–1.25	—	126/1228	10.3%	0.61	0.48–0.77	—	151/994	15.2%	1.73	1.37–2.20	—
Education
No Qualifications	371/3172	11.7%	68/562	12.1%	1		0.8232	37/322	11.5%	1		0.7791	117/1224	9.6%	1		< 0.0001	133/985	13.5%	1		< 0.0001
Other non-university qualifications	1484/3172	46.8%	258/562	45.9%	0.87	0.64–1.18	—	145/322	45.0%	0.95	0.65–1.39	—	589/1224	48.1%	1.43	1.12–1.82	—	520/985	52.8%	0.93	0.73–1.18	—
University degree or higher	1317/3172	41.5%	236/562	42.0%	0.86	0.63–1.17	—	140/322	43.5%	1.03	0.70–1.52	—	518/1224	42.3%	1.41	1.10–1.80	—	332/985	33.7%	0.58	0.45–0.74	—
Smoking
Never smoker	1264/3213	39.3%	162/566	28.6%	1		< 0.0001	84/324	25.9%	1	0.33–0.59	< 0.0001	291/1240	23.5%	1		< 0.0001	0/1011	0.0%	1
Ex-smoker	938/3213	29.2%	177/566	31.3%	1.58	1.25–2.00	—	100/324	30.9%	1.67	1.23–2.27	—	347/1240	28.0%	1.95	1.62–2.35	—	0/1011	0.0%	—	—	—
Current	1011/3213	31.5%	227/566	40.1%	1.97	1.58–2.46	—	140/324	43.2%	2.26	1.70–3.01	—	601/1240	48.5%	4.88	4.01–5.93	—	1011/1011	100.0%	—	—	—
Recreational drugs used^a
None	2016/3258	61.9%	287/568	50.5%	1		0.0017	149/325	45.9%	1		< 0.0001	0/1242	0.0%	—		—	410/1011	40.6%	1		< 0.0001
1 or 2 non-injection	696/3258	21.4%	163/568	28.7%	1.50	1.21–1.87	—	98/325	30.2%	2.01	1.53–2.63	—	696/1242	56.0%	—	—	—	337/1011	33.3%	3.59	2.98–4.31	—
3+ non-injection	472/3258	14.5%	102/568	18.0%	1.34	1.04–1.73	—	70/325	21.5%	2.13	1.57–2.89	—	472/1242	38.0%	—	—	—	226/1011	22.4%	3.52	2.84–4.34	—
Injection drug use	74/3258	2.3%	16/568	2.8%	1.46	0.82–2.62	—	8/325	2.5%	1.51	0.71–3.20	—	238/1242	6.0%	—	—	—	74/1011	3.8%	4.02	2.52–6.43	—
Sexual behaviour
Condom-less vaginal or anal sex^a	1082/3258	33.2%	202/568	35.7%	1.02	0.84–1.24	0.8041	128/325	39.4%	1.32	1.04–1.67	0.0218	625/1242	50.3%	3.46	2.95–4.05	< 0.0001	384/1011	38.0%	1.33	1.14–1.55	0.0004
> 10 new partners in last 12 months	554/3258	17.0%	113/518	21.8%	1.14	0.90–1.45	0.2690	79/305	25.9%	1.61	1.11–1.93	0.0009	413/1173	35.2%	6.43	5.15–8.04	< 0.0001	208/928	22.4%	1.42	1.17–1.73	0.0004
'Less likely to use a condom'	444/3258	13.6%	93/541	17.2%	1.27	0.96–1.60	0.1040	50/314	15.9%	1.21	0.81–1.55	0.4882	236/1212	19.4%	1.88	1.53–2.31	< 0.0001	138/970	14.2%	0.95	0.77–1.18	0.6657

Quoted P-values refer to those from calculation of χ². Odds Ratios (OR) are unadjusted.
ART, antiretroviral therapy; CI, confidence interval; GAD-7, General Anxiety Disorder-7; MSM, men who have sex with men; OR, odds ratio; PHQ-9, Patient Health Questionnaire-9.
^aIn the previous 3 months.

Table 2. Distribution and interrelationships of alcohol use and dependency variables
Alcohol use	Total		Participants reporting > 20 units alcohol/week from AUDIT questions^a		Participants reporting alcohol dependence: CAGE score ≥ 2 and current alcohol consumption
AUDIT: alcohol frequency
Never	576/3212	17.9%	0/325	0.0%	0/566	0.0%
Monthly or less	681/3212	21.2%	0/325	0.0%	66/566	11.7%
Two toi four times Monthly	690/3212	21.5%	0/325	0.0%	95/566	16.8%
Two to three times Weekly	694/3212	21.6%	38/325	11.7%	161/566	28.4%
Four-plus times a week	571/3212	17.8%	287/325	88.3%	244/566	43.1%
AUDIT: units when drinking
Never	576/3160	18.2%	0/325	0.0%	0/561	0.0%
1 or 2	988/3160	31.3%	0/325	0.0%	81/561	14.4%
3 or 4	751/3160	23.7%	0/325	0.0%	137/561	24.4%
5 or 6	464/3160	14.7%	143/325	44.0%	156/561	27.8%
7–9	234/3160	7.4%	77/325	23.7%	105/561	18.7%
10 or more	147/3160	4.7%	105/325	32.3%	82/561	14.6%
AUDIT score
0	637/3221	19.8%	—		0/561	0.0%
1 or 2	830/3221	25.8%	—		65/561	11.6%
3 or 4	907/3221	28.2%	—		130/561	23.2%
5 or 6	665/3221	20.6%	143/325	44.0%	248/561	44.2%
7 or 8	182/3221	5.7%	182/325	56.0%	118/561	21.0%
AUDIT: 20+ units Weekly	325/3160	10.3%	325/325	100.0%	187/561	32.9%
CAGE: answered 'yes' to
Have you ever felt you should cut down your drinking?	974/3221	30.2%	260/325	80.0%	545/568	96.0%
Have people annoyed you by criticizing your drinking?	295/3221	9.2%	110/325	33.8%	263/568	46.3%
Have you ever felt bad or guilty about your drinking?	530/3221	16.5%	158/325	48.6%	484/568	85.2%
Have you ever had a drink first think in the morning to steady your nerves or get rid of a hangover?	192/3221	6.0%	59/325	18.1%	144/568	25.4%
CAGE score
0	2103/3221	65.3%	50/325	15.4%	0/568	0.0%
1	547/3221	17.0%	88/325	27.1%	0/568	0.0%
2	332/3221	10.3%	96/325	29.5%	330/568	58.1%
3	176/3221	5.4%	57/325	17.6%	176/568	31.0%
4	63/3221	2.0%	34/325	10.5%	62/568	10.9%
Alcohol dependency CAGE score ≥ 2 and current alcohol consumption	568/3221	17.6%	187/325	57.5%	568/568	100.0%

^aDerived from multiplication of alcohol frequency and units when drinking. AUDIT score deriver from modifiedversion of AUDIT-Cusing first two questions only.

Table 3. Cross-sectional association of lifestyle factors (alcohol use, recreational drug use, smoking) with antiretroviral therapy (ART) non-adherence among people on anitretroviral therapy (ART) who started ART at least 6 months prior to the questionnaire. N = 2418
	n	Column %	Unajusted Odds Ratio (OR) of non-adherence			aOR of non-adherence (age, gender/sexual orientation and ethnicity)			aOR of non-adherence (age, gender/sexual orientation, ethnicity, hardship and education)
	n	Column %	OR	95% CI	P(LR)	aOR	95% CI	P (LR)	aOR	95% CI	P (LR)
AUDIT points					P = 0.457 Linear test for trend, P = 0.621			P = 0.013 Linear test for trend, P = 0.004			P = 0.0074 Linear test for trend, P = 0.002
0	473/2413	19.6%	1			1			1
1 or 2	649/2454	26.9%	0.84	0.58–1.20	0.333	0.91	0.63–1.30	0.588	0.98	0.67–1.42	0.924
3 or 4	696/2454	28.8%	0.79	0.55–1.12	0.187	1.01	0.70–1.47	0.949	1.21	0.82–1.77	0.340
5 or 6	472/2454	19.6%	1.04	0.72–1.51	0.839	1.56	1.05–2.33	0.029	1.80	1.19–2.71	0.005
7–8	123/2454	5.1%	1.20	0.71–2.02	0.884	1.83	1.05–3.19	0.033	1.94	1.10–3.42	0.022
> 20 units alcohol/week
No	2185/2410	90.7%	1			1			1
Yes	225/2410	9.3%	1.39	0.97–1.99	0.070	1.77	1.21–2.58	0.005	1.79	1.22–2.63	0.003
Alcohol dependence^a
No	1996/2413	82.7%	1			1			1
Yes	417/2413	17.3%	2.01	1.53–2.64	< 0.001	2.20	1.66–2.92	< 0.001	2.15	1.61–2.88	0.011
CAGE score
0	a592/2413	66.0%	1		P = 0.020 Linear test for trend, P < 0.001	1		P < 0.001 Linear test for trend, P < 0.001	1		P < 0.001 Linear test for trend, P < 0.001
1	404/2413	16.7%	1.16	0.83–1.61	0.361	1.18	0.84–1.66	0.345	1.11	0.79–1.58	0.274
2	247/2413	10.2%	1.64	1.14–2.38	0.008	1.80	1.24–2.62	0.002	1.75	1.19–2.60	0.220
3	129/2413	5.4%	2.18	1.41–3.39	0.001	2.46	1.56–3.67	< 0.001	2.43	1.53–3.87	0.181
4	42/2413	1.7%	4.66	2.54–7.54	< 0.001	5.10	2.72–9.56	< 0.001	4.20	2.19–8.05	0.003
Smoking status
Never	964/2406	40.1%	1		P < 0.001	1		P < 0.001	1		P < 0.001
Ex	724/2406	30.1%	0.78	0.57–1.07	0.125	1.12	0.80–1.56	0.519	1.08	0.76–1.52	0.670
Current	718/2406	29.8%	1.56	1.19–2.05	0.001	2.20	1.61–3.01	< 0.001	1.82	1.31–2.52	< 0.001
Recreational drugs used^b
None	1520/2418	62.9%	1	P < 0.001		1	P < 0.001		1	P < 0.001
1 or 2 non-injection	518/2418	21.4%	1.20	0.90 −1.61	0.213	1.62	1.16–2.27	0.005	1.54	1.10–2.17	0.013
3+ non-injection	328/2418	13.6%	1.32	0.95–1.85	0.102	1.96	1.32–2.89	0.001	2.03	1.36–3.02	0.001
Injection drug use	52/2418	2.2%	3.97	2.26–6.99	< 0.001	5.71	3.11–10.49	< 0.001	5.48	2.93–10.27	< 0.001

aOR, adjusted odds ratio (in first models adjusted for gender/sexual orientation, ethnicity and age; in second models additionally adjusted for financial hardship and education); CI, confidence interval; LR, likelihood ratio; AUDIT alcohol consumption score derived from modified version of AUDIT-C using first two questions only
^aAlcohol dependence: CAGE score ≥ 2 and current alcohol consumption.
^bDrugs use in the previous 3 months. ART non-adherence was defined as missing ≥ 2 consecutive days of ART on two or more occasions in the past 3 months.

Table 4. Cross-sectional association of lifestyle factors (alcohol use, recreational drug use, smoking) with viral non-suppression among people on antiretroviral therapy (ART) who started ART at least 6 months prior to the viral load (VL) measurement. N = 2459
n = 2459			Unadjusted odds ratio (OR) of detectable VL			aOR of detectable VL (age, gender/sexual orientation and ethnicity)			aOR of detectable VL (age, gender/sexual orientation, ethnicity, hardship and education)
Risk factor	n	Column %	OR	95% CI	P(LR)	aOR	95% CI	P (LR)	aOR	95% CI	P (LR)
AUDIT score
					P = 0.038 Linear test for trend, P = 0.919			P = 0.081 Linear test for trend, P = 0.435			P = 0.117 Linear test for trend, P = 0.504
0	483/2454	19.7%
1 or 2	662/2454	27.0%	0.78	0.54–1.14	0.206	0.85	0.57–1.23	0.381	0.94	0.63–1.41	0.773
3 or 4	707/2454	28.8%	0.55	0.37–0.82	0.003	0.65	0.42–0.99	0.041	0.70	0.45–1.09	0.111
5 or 6	477/2454	19.4%	0.61	0.57–1.28	0.455	1.08	0.69–1.67	0.764	1.23	0.78–1.92	0.380
7–8	125/2454	5.1%	0.93	0.50–1.72	0.803	1.16	0.61–2.22	0.641	1.12	0.57–2.22	0.738
> 20 units alcohol/week
No	2221/2450	90.7%	1						1
Yes	229/2450	9.3%	1.12	0.72–1.75	0.615	1.32	0.83–2.08	0.246	1.23	0.77–1.96	0.396
Alcohol dependence^a
No	2028/2454	82.6%	1						1
Yes	426/2454	17.4%	1.52	1.10–2.08	0.011	1.54	1.11–2.13	0.011	1.52	1.09–2.13	0.018
CAGE Score
0	1615/2454	65.8%	1		P = 0.022 Linear test for trend, P = 0.001	1		P = 0.030 Linear test for trend, P = 0.002	1		P = 0.073 Linear test for trend, P = 0.001
1	413/2454	16.8%	0.80	0.53–1.19	0.274	0.80	0.53–1.20	0.282	0.80	0.53–1.20	0.289
2	247/2454	10.1%	1.27	0.82–1.92	0.220	1.30	0.84–2.00	0.173	1.32	0.84–2.04	0.229
3	136/2454	5.5%	1.41	0.82–2.38	0.181	1.43	0.83–2.44	0.166	1.41	0.81–2.44	0.230
4	43/2454	1.8%	2.94	1.45–6.25	0.003	2.78	1.32–5.88	0.017	2.33	1.09–5.00	0.029
Smoking status
Never	982/2446	40.2%	1		P< 0.001	1		P = 0.001	1		P = 0.005
Ex	731/2446	29.9%	0.74	0.52–1.06	0.097	0.89	0.61–1.30	0.552	0.89	0.60–1.32	0.561
Current	733/2446	30.0%	1.49	1.10–2.03	0.010	1.71	1.21–2.41	0.002	1.58	1.10–2.27	0.013
Recreational drugs used^b
None			1		P= 0.167	1		P= 0.007	1		P= 0.263
1 or 2 non-injection	527/2459	21.9%	0.87	0.61–1.23	0.432	0.96	0.66–1.39	0.836	0.91	0.62–1.35	0.690
3+ non-injection	332/2459	13.8%	0.93	0.61–1.40	0.711	1.01	0.64–1.60	0.928	1.00	0.62–1.59	0.972
Injection drug use	53/2459	2.2%	2.17	1.07–4.40	0.032	2.25	1.08–4.69	0.031	2.11	1.00–4.47	0.051

aOR, adjusted odds ratio (adjusted for gender/sexual orientation, ethnicity and age); CI, confidence interval; LR, likelihood ratio; AUDIT alcohol consumption score derived from modified version of AUDIT-C using first two questions only. Detectable VL was defined as VL > 50 copies/mL
^aAlcohol dependence: CAGE score ≥ 2 and current alcohol consumption.
^bDrugs use in the previous 3 months.

Table 5. Longitudinal association of lifestyle factors with hazards of viral rebound (> 200 copies/mL) during follow-up in people from the Royal Free study site who consented to data linkage, were on ART with VL ≤ 50 copies/mL at study entry and started ART at least 6 months prior to the baseline VL measurement. N = 592
n = 592			Unadjusted hazards ratio (HR) of viral rebound			aHR of viral rebound (age, gender/sexual orientation and ethnicity)			aHR of viral rebound (age, gender/sexual orientation, ethnicity, hardship and education)
Risk factor	n	Column %	HR	95% CI	P (LR)	aHR	95% CI	P (LR)	aHR	95% CI	P (LR)
AUDIT points
			P = 0.794 Linear test for trend, P = 0.592			P = 0.452 Linear test for trend, P = 0.051			P = 0.332 Linear test for trend, P = 0.031
0	122/591	20.6%	1			1			1
1 or 2	151/591	25.6%	1.12	0.64–1.96	0.681	1.23	0.70–2.16	0.468	1.38	0.77–2.48	0.283
3 or 4	175/591	29.6%	0.85	0.48–1.49	0.563	1.11	0.61–2–04	0.724	1.18	0.64–2.17	0.590
5 or 6	126/591	21.3%	0.99	0.55–1.81	0.986	1.38	0.73–2.61	0.321	1.33	0.70–2.54	0.376
7–8	17/591	2.9%	1.44	0.49–4.19	0.506	3.02	0.99–9.19	0.052	3.65	1.19–11.19	0.024
> 20 units alcohol/week^a
No	542/590	91.9%	1			1			1
Yes	48/590	8.1%	1.18	0.62–2.27	0.622	1.60	0.82–3.00	0.195	1.40	0.72–2.74	0.345
Alcohol dependence^a
No	486/591	82.2%	1			1			1
Yes	105/591	17.8%	1.44	0.90–2.28	0.126	1.65	1.03–2.63	0.045	1.66	1.03–2.66	0.045
					P= 0.210 Linear test for trend, P= 0.006			P= 0.151 Linear test for trend, P= 0.005			P = 0.257 Linear test for trend, P = 0.041
CAGE score
0	399/591	67.5%	1			1			1
1	87/591	14.7%	0.81	0.44–1.46	0.490	0.89	0.49–1.62	0.701	0.87	0.48–1.58	0.641
2	59/591	10.0%	1.16	0.62–2.20	0.640	1.42	0.75–2.71	0.283	1.63	0.85–3.13	0.145
3	36/591	6.1%	1.31	0.63–2.74	0.459	1.46	0.70–3.06	0.312	1.35	0.64–2.82	0.429
4	10/591	1.7%	3.66	1.33–10.06	0.012	3.86	1.39–10.68	0.009	2.63	0.92–7.51	0.071
Smoking status
Never	213/588	36.2%	1		P = 0.448	1		P = 0.251	1		P = 0.580
Ex	189/588	32.1%	1.00	0.62–1.62	0.996	1.30	0.79–2.15	0.306	1.30	0.78–2.16	0.310
Current	186/588	31.6%	1.30	0.82–2.06	0.261	1.50	0.92–2.43	0.102	1.20	0.72–1.99	0.490
Recreational drugs used^b
None	322/592	54.4%	1		P = 0.192	1		P = 0.007	1		P = 0.013
1 or 2 non-injection	147/592	24.8%	0.68	0.40–1.16	0.155	0.97	0.54–1.74	0.922	0.82	0.46–1.50	0.538
3+ non-injection	106/592	17.9%	1.47	0.91–2.35	0.113	2.16	1.22–3.82	0.008	1.82	1.12–3.57	0.020
Injection drug use	17/592	2.9%	2.49	1.07–5.78	0.034	3.37	1.36–8.39	0.009	2.73	1.08–6.89	0.033

aHR, adjusted hazard ratio (in first models adjusted for gender/sexual orientation, ethnicity and age; in second models additionally adjusted for financial hardship and education); CI, confidence interval; LR, likelihood ratio. AUDIT alcohol consumption score derived from modified version of AUDIT-C using first two questions only.
^aAlcohol dependence: CAGE score ≥ 2 and currently drinking.
^bDrug use in the 3 months prior to taking the questionnaire. Viral rebound was defined as first VL > 200 copies/mL. In the Royal Free clinic cohort 802 patients consented to prospective data collection. Of these, 596 (74.3%) were MSM, 75 (9.4%) were heterosexual men and 131 (16.3%) were women. Mean (± SD) age was 46.5 (± 9.1) years; 615 (76.7%) were white and 100 (12.5%) were of black African ethnicity. A total of 55 (8.4%) of the cohort drank > 20 units alcohol/week, while 112 (17.2%) were classified as having alcohol dependence; 203 (31.2%) reported being current smokers at the time of questionnaire, and 296 (45.1%) reported taking recreational drugs in the past 3 months; 73.8% (n = 592) of individuals with a viral load (VL) < 50 HIV-1 RNA copies/mL and who had started ART at least 6 months before the VL measurement were included in the above analysis.