High prevalence of recreational and illicit drug use in German people living with HIV with a potential for drug–drug interactions with antiretroviral therapy

Abstract

Recreational drug use is higher in people living with HIV (PLHIV) than in the general population in Europe. This use increases the risk for drug-drug interactions (DDIs) and adverse events. We assessed the prevalence and clinical consequences of substance abuse among PLHIV. BESIDE was a cross-sectional, multi-center study in 2016/18, evaluating comorbidities, polypharmacy and recreational/illicit drug use in PLHIV on antiretroviral therapy (ART) in Germany. Legal and illicit drug use was recorded using two anonymous patient questionnaires one year apart (Q1 and Q2). The BESIDE study population consisted of 453 PLHIV (22% female, median age 46 years). Recreational drug use was reported by the majority (Q1: ever used 73%, within previous 6 months 56%): nitrite inhalants (“poppers”), cannabis and PDE-5 inhibitors were common across all age groups; ecstasy, (meth-)amphetamine and gamma-hydroxybutyrate/gamma-butyrolactone were predominantly reported by younger PLHIV. Based on Q2, two-thirds of PLHIV (67%) had been informed about potential risks of drug abuse by their doctors, whereas one-third (33%) had talked to their doctors on their own initiative with only 7% considering drug use in combination with ART a problem. Strikingly, 44% and 42% had undergone medical treatment or had been hospitalized due to drug use. These data emphasize the high clinical relevance of recreational drug use in PLHIV and the need for treating physicians to pro-actively communicate the potential risks.

Keywords

Europe antiretroviral therapy human immunodeficiency virus toxicity antiviral

Introduction

Consumption of recreational drugs including new psychoactive substances has spread dramatically over several European countries.¹ With an increasing prevalence of illicit drug use, the management of drug-induced acute disorders has become a growing challenge for the health systems.¹ Data suggest an even higher use of recreational drugs by people living with HIV (PLHIV) than the general population.^2,3 Given the problems of illicit drug use and ageing in PLHIV with an increased prevalence of comorbidities, physicians involved in the treatment of HIV are facing new challenges in daily patient care.^4–6 This includes paying special attention to potential drug-drug-interactions (DDIs) between antiretroviral therapy (ART), prescribed co-medications and recreational drugs.⁶ DDIs and known toxicities of recreational or illicit drugs may induce medical problems.⁷ Of note, a meta-analysis on psychiatric disorders showed that men having sex with men (MSM) (two-thirds of PLHIV in Germany are MSM) had a 1.5- and 2.4-fold higher risk for alcohol and other illicit drug abuse, respectively, over 12 months than heterosexual people.⁸ The national drug report for Germany in 2019 shows a gradual shift in the prevalence of recreational/illicit drug use from older to younger age groups.⁹ Younger PLHIV may therefore be at risk for DDIs between ART and illicit drugs. Yet, the use of recreational drugs on HIV-related outcomes remains understudied.

The objectives of the BESIDE study, an observational study conducted in Germany, were to quantify the prevalence of comorbidities, the use of concomitant medication and the use of recreational/illicit drugs in PLHIV on ART. The present analysis of the final BESIDE dataset describes the prevalence of recreational drug consumption and its potential implications on medical management and need for further interventions in a representative sample of PLHIV in Germany.

Methods

Study design, setting and outcomes of interest

BESIDE was an observational cross-sectional multicenter (n = 20), non-interventional study in adult PLHIV taking ART in Germany from October 2016 until the end of 2018. To minimize selection bias, patient recruitment was consecutive and sampling was stratified by region and age group based on the epidemiologic data in Germany. Collection of data was pseudonymized and focused on comorbidities and concomitant medication including over-the-counter (OTC) drugs and supplements. The planned sample size was 450 patients from 20 German centers (with a maximum of 30 patients per center), allowing the detection of concomitant non-HIV comedication used by as few as 1.0% of the target population with a power of 95%. This takes into account that approximately 25% of the recruited patients are assumed to provide missing data and/or incomplete recall information. Results will be published elsewhere.

Aside from morbidity and co-medications, the BESIDE study also collected data on alcohol consumption, smoking and current, recent or prior use of recreational/illicit drugs including type of psychoactive substances. These data were obtained using an anonymous modified self-report EMIS questionnaire (Q1, see supplemental material available online).^12,13 A second anonymous questionnaire (Q2, see supplemental material available online) focused on the clinical relevance of drug use one year later. Patients were asked about their drug use in general, drug use to stimulate sex life, needle sharing, knowledge of potential risks associated with recreational drug use, and history of therapeutic interventions secondary to the consumption of drugs. Further, they were asked to comment on patient-doctor communication on the topic of drugs. For analyses of potential DDIs between different ART regimens and recreational drugs, the HIV Liverpool Drug Interactions Database was consulted.¹⁴ Due to the anonymous nature of the self-report questionnaires Q1 and Q2, information bias should have been avoided. It also made linking of Q1 to Q2 or individual patient records impossible. The only demographic parameter captured in both questionnaires was the age group for respective stratification.

Study population

Inclusion criteria were age ≥18 years, confirmed HIV-1 infection, on ART and written informed consent. The inclusion of patients was independent from any use of certain medications. Since Q1 and Q2 were anonymous, there was no obligation for patients to complete either questionnaire. Patients were excluded, if investigators considered information provided on concomitant diseases and co-medication as unreliable.

Regulatory requirements and quality control

The observational plan was approved by the corresponding ethics committee (No. 16046), as was amendment 1 implementing the 2^nd survey approximately one year later. All subjects had to give written informed consent prior to enrollment in the study.

Statistical methods

All parameters were evaluated in a descriptive manner using descriptive statistics. Of note, all data were evaluated on an as-observed basis, i. e. missing answers were ignored. Data were presented as median values (plus ranges) or relative frequencies with the denominator being the total number of respondents to the specific question. Results were presented for the total study population, i. e. all observed cases for each item, and stratified by age group (<30 years/30–39 years/40–49 years/50–59 years/≥60 years). Statistical analyses were performed using the software package SAS 9.4 (SAS Institute Inc., Cary, NC, USA).

Results

Study population

Between the last quarter of 2016 and the first quarter of 2017, 453 eligible patients from 20 German centers were enrolled in the study (full analysis set, FAS), with 22% female patients. The median age of the study population was 46 years (range 18–86 years). Baseline characteristics of the FAS are shown in Table 1. The majority of the FAS (92%, 415 patients) completed Q1 on recreational drug use.

Table 1.

Characteristics of the study population (full analysis set, FAS).

	N	n (%)/median (range)
Gender, male/female, n (%)	453	355/98 (78.4/21.6%)
Time living with HIV (years), median (range)	453	9 (0–32)
Clinical AIDS (CDC C), n (%)	420	68 (15.0)
CD4 cell count (cells/µL), median (range)	448	650 (31–2,144)
HIV RNA level < limit of quantification, n (%)	448	341 (75.3)
Nicotine use (within the last 7 days), n (%)	411^a	200 (48.7)
Never smoked, n (%)		102 (24.8)
Alcohol use (within the last 7 days), n (%)	409^a	227 (55.5)
Alcohol use >6 months ago, n (%)		45 (11.0)
No use of alcohol (ever), n (%)		31 (7.6)

^aData from respondents of the anonymous questionnaire 1 (Q1).

A subset of 293 study participants completed Q2 focusing on patient-doctor communication about drug use, patient knowledge of clinical consequences of drug use and the need for therapeutic intervention due to drug use. The age distribution of patients in the three analysis sets (FAS, patients having completed Q1 and Q2) is shown in Figure 1. Whereas the age distributions of the FAS and of patients completing Q1 were comparable to that of the population of PLHIV in Germany, patients between 30–49 years were somewhat under-represented in the cross-sectional survey Q2.

Figure 1.

Age distribution of the analysis populations (FAS [full analysis set of BESIDE, respondents of questionnaires Q1 and Q2] in comparison to people living with HIV [PLHIV] in Germany [smoothed line]; based on estimates of the Robert-Koch Institute for the year 2017¹¹).

Prevalence of drug use

In total, 90% (375/415) of patients reported having consumed drugs (including alcohol and/or tobacco) within the last 6 months and 78% (324/415) of patients within the last 7 days (Q1). Alcohol and/or tobacco use within the past 6 months were reported by 81% (333/409) and 56% (231/411) of patients and within the last 7 days by 56% (227/409) and 49% (200/411), respectively. After excluding alcohol and tobacco use, 73% (303/415) of patients have ever consumed recreational drugs, 56% of patients (230/413; 413 having provided information on time-lines) during the past 6 months, 32% (131/413) during the previous 7 days. Very recent use (≤7 days) was highest in the age group 20–29 years (40.5%) (with a trend towards lower use in patients >50 years (27%)).

Of note, about the same proportion of PLHIV completing Q2 one year later consumed recreational drugs (76%; 223/293), whereas 28% (81/293) had used these drugs in the preceding 6 months. The proportions of drug users based on Q1 and on Q2 data across age groups are depicted in Figure 2(a). In Q2, younger PLHIV (≤39 years) more often stated drug consumption than older PLHIV, and rates of drug consumption in these age groups were higher than in Q1 (<30 years Q1: 68%, Q2: 80%; 30–39 years: Q1: 79%, Q2: 89%). The median age at time of first recreational/illicit drug use was 20 years (interquartile range, IQR: 11–55 years).

Figure 2.

(a) Proportion of patients consuming recreational drugs (excluding alcohol/tobacco) stratified by age group ‒ comparison of respondents of questionnaires Q1 (n = 415) and Q2 (n = 293). (b) Drugs consumed by people living with HIV stratified by age category (<50 years versus ≥50 years) (based on questionnaire 1); (drugs used in >10% of PLHIV in either age category and difference in prevalence between age categories ≥7%).

Most frequently consumed (>15% of patients) recreational drugs according to Q1 were: nitrite inhalants (ever use 52%, recent use [within the previous 6 months] 36%), cannabis (ever use 47%, recently 23%), PDE-5 inhibitors (ever use 39%, recently 26%), cocaine (ever use 29.5%, recently 9%), ecstasy (ever use 27%, recently 9%), amphetamine (ever use 27%, recently 10%), sedatives/tranquilizers (ever use 18%, recently 7%), and gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL) (ever use 17%, recently 6%). Of these, ecstasy, amphetamines and GHB/GBL were predominantly consumed by patients <50 years and sedatives/tranquilizers by patients ≥50 years (Figure 2(b)). Based on Q2, 22% of PLHIV (47/213) used drugs to stimulate their sex lives, with the highest proportion among middle-aged people (30–39 years: 30% and 40–49 years: 28%); 8% of the patients (n = 17/201) had shared needles and/or syringes with another person for drug use.

Potential drug–drug interactions between recreational drugs and ART

Figure 3 shows the proportion of patients using recreational drugs and their potential for DDI with ART. Overall, 50% (208/415; Q1) of patients consumed drugs with a potential to interact with an antiretroviral, requiring additional monitoring or dose adjustments, 30% (126/415) of patients within the last 6 months. Moreover, about half of patients (55% [227/415]) consumed drugs which should not be co-administered with some antiretrovirals, 34% (142/415) of patients within the last 6 months.

Figure 3.

Proportion of patients consuming recreational drugs and their potential of drug-drug interactions (DDIs) with any antiretroviral therapy (drug consumption based on Q1; DDIs according to the HIV Liverpool Drug Interactions Database¹⁴) (patients may be allocated to more than one potential-for-interaction category).

Patient–HIV doctor communication

Almost three-quarters of patients (71% [207/290]) had been asked about drug use by their HIV doctors and 67% (194/290) had been informed by their HIV doctors on potential risks and interactions associated with the use of recreational drugs and their current ART (Figure 4). The majority of patients, i. e. 41% (120/290) and 27% (77/290) were feeling very well or well informed. The rates were comparable across age groups (data not shown). Merely 5% (15/290) of the patients felt that they were not sufficiently or not at all informed about this topic. Of note, 33% (65/198) of patients had talked to their doctor about their drug use out of their own initiative and 7% (15/202) saw a problem in the use of drugs in combination with ART.

Figure 4.

Communication between HIV doctor and patient stratified by age group: Proportion of patients i) being asked about recreational drug use by their doctor (left column), ii) having been informed about potential risks and drug-drug interactions, iii) having talked to doctor about their drug use on their own initiative and iv) conceding a problem in the concomitant use of recreational drugs and HIV therapy (right column).

Clinical implication of drug use (medical treatment and/or hospitalization)

A relatively high proportion of patients had received medical treatment at some point in time (44% [86/196]) or had ever been hospitalized (42% [81/195]) due to drug consumption. The rates were high across all age groups and numerically peaked in younger patients aged <30 years, 60% and 65% of who had received medical treatment (12/20) or had been hospitalized (13/20), respectively (Figure 5). This was consistent with a high number of patients who reported having had problems with their ART (36% [70/195]; <30 y: 67% [12/18)] or even having had to switch their ART (31% [62/199]; <30 y: 60% [12/20]) due to recreational drug use.

Figure 5.

Medical complications due to recreational drug use: Problems with ART and therapeutic intervention due to drug use stratified by age group (based on questionnaire 2; as-observed data).

Discussion

Recreational/illicit drug use among PLHIV in Germany is common as shown in BESIDE, a representative cohort of PLHIV taking ART in Germany with data collected using two cross-sectional surveys between 2016 and 2018. Approximately three-quarters of study participants indicated having experience with drug consumption; recent use (within the previous 6 months) was stated by about half of patients (56%), with a trend to more recent use in younger patients. The most commonly used drugs were nitrite inhalants, PDE-5 inhibitors, and cannabis; 36%, 26% and 23% of PLHIV reported use of these drugs in the past 6 months, respectively. Apart from cannabis, patterns of drug use differed between age groups. Younger patients predominantly consumed drugs such as ecstasy, amphetamine, GHB/GBL, methamphetamine and ketamine. Older patients above 50 years predominantly reported the use of sedatives or heroin, the latter mainly in the past. Of note, although the age distribution for the full analysis set of the BESIDE study and for the respondents of the first questionnaire matches the age-dependent distribution of the population of PLHIV in Germany, comparisons of drug use between age groups may be limited by differing, and in part small, sample sizes, especially in the youngest and oldest age groups.

Compared to the general population in Germany, drug use was higher in PLHIV in the BESIDE study. An epidemiological survey in Germany included 9,227 adults aged 18 to 64 years and found that 8% of participants consumed at least one illicit drug (out of cannabis, [meth-]amphetamine, ecstasy, LSD [lysergic acid diethylamide], heroin, other opiates, cocaine/crack, hallucinogenic mushrooms and new psychoactive substances) in the past 12 months. The most commonly used drugs were cannabis (reported by 7% of respondents in comparison to 23% during the last 6 months in BESIDE), followed by amphetamine (1% vs. 10% in BESIDE) and cocaine (<1% vs. 9%), crack (<1% vs. 0.5%) and ecstasy (1% vs. 9%).¹⁵

In the second questionnaire of BESIDE, about one in five PLHIV reported using drugs to stimulate their sex life. This proportion seems to be somewhat lower than reported in the first questionnaire focusing on the specific drugs commonly used as chemsex drugs. On the one hand, the difference in numbers between those participants using the above mentioned chemsex drugs and those reporting drug use in a sexual context could be partly attributed to the lower sample size completing Q2 in comparison to Q1, and on the other hand also to an insufficient awareness of the connection between sexual behavior and use of chemsex drugs.

Other reports focusing on MSM have highlighted the rise of chemsex: using stimulant drugs such as mephedrone, crystal meth, GHB, or others, taken before or during sex.^12,16,17 A cross-sectional study in the United Kingdom investigated the association of polydrug use and sexual behavior in adult MSM living with HIV from eight HIV outpatient clinics between 2011 and 2012. Half of 2,248 MSM (51%) had used recreational drugs in the previous 3 months. The prevalence of cannabis (21%), ketamine (13%), GHB/GBL (10%) or mephedrone (7%) use was similar to those reported in BESIDE.¹⁸ Recent use of cocaine was even higher in the UK with 20% of MSM. Of note, these drugs can cause serious adverse effects and are known to be associated with polydrug consumption.¹⁹

Approximately one-third of participants in the BESIDE study had recently (within the last 6 months) used recreational drugs, which should not be coadministered with some antiretroviral substances. About the same proportion had recently used recreational drugs with an interaction potential that would require monitoring or dose adjustments. Given these high numbers, younger PLHIV in particular need to be informed about the risk for potential DDIs with drugs not prescribed by the physician and not mentioned by the patient on his own initiative. Since younger PLHIV may regularly use recreational drugs, a thorough drug history needs to be taken and the risk for DDIs should be carefully evaluated when selecting the appropriate ART. Of note, we evaluated all potential DDIs with the available antiretroviral drugs. Since the questionnaires were anonymous, it was not possible to link recreational drug use with HIV-related data of the patient such as antiretroviral regimens at the time of the cross-sectional questionnaires. Therefore, our goal was to evaluate the maximum potential for interaction with ART, emphasizing a) the necessity of a trustful patient-doctor communication to identify potential problems with ART, and b) the importance of focusing on antiretroviral drugs with a low potential for DDIs in people likely to consume recreational drugs. Of note, in the BESIDE cohort, recruited in the years 2016–2017, most commonly used antiretroviral drugs (in >10% of patients) with a known potential for DDIs were cobicistat-boosted elvitegravir (14.8%), ritonavir- or cobicistat-boosted darunavir (13.9), rilpivirine (11.9%) and nevirapine (10.2%).

Although patients across all ages felt that they were informed about the potential risks of recreational drug consumption, the number of therapeutic interventions such as medical treatments and hospitalizations is alarming, particularly among younger patients. This emphasizes the need for an open and confident communication between patients and doctors, and further good training in communication skills and in motivational interviewing as well as adequate knowledge about the risks of drug consumption.^19,20 Of note, only one-third of drug-using PLHIV proactively sought consultation from their doctors. A minority realized that the concomitant use of recreational drugs and ART could be harmful. This demonstrates the need for pro-active education, especially among younger patients, by the treating physicians.

Conclusion

The BESIDE study revealed that recreational and illicit drug use is common among antiretrovirally-treated PLHIV in Germany, often resulting in DDIs, need for medical treatment or hospitalization. This underscores the urgent need for harm reduction involving a pro-active and confident patient-doctor communication, information on the potential risks by treating physicians and the selection of an appropriate ART regimen.

Supplemental Material

sj-pdf-1-std-10.1177_0956462420959169 - Supplemental material for High prevalence of recreational and illicit drug use in German people living with HIV with a potential for drug–drug interactions with antiretroviral therapy

Supplemental material, sj-pdf-1-std-10.1177_0956462420959169 for High prevalence of recreational and illicit drug use in German people living with HIV with a potential for drug–drug interactions with antiretroviral therapy by B Funke, CD Spinner, S Esser, HJ Stellbrink, A Stoehr, E Wolf, C Koegl, J Bruening and V Witte in International Journal of STD & AIDS

Footnotes

Acknowledgements

We thank all participating patients, investigators and study nurses involved in the BESIDE study. Statistical analyses were performed by Alcedis GmbH, Giessen, Germany. Support in medical writing was provided by MUC Research GmbH, Munich, Germany.

Declaration of conflicting interests

BF, JB and VW are current employees of MSD Sharp & Dohme GmbH. CDS, SE, HJS, AS, EW and CK have a financial relationship relevant to this publication with MSD Sharp & Dohme GmbH. CSD has received honoraria for consulting or speaking at educational events from AbbVie, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Hexal/Teva, Hormosan, Janssen-Cilag, MSD Sharp & Dohme, Roche, and ViiV Healthcare. He has received research grants from Gilead, Janssen-Cilag and ViiV Healthcare. SE has received honoraria for consulting or speaking at educational events from AbbVie, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Hexal/Teva, Janssen-Cilag, MSD Sharp & Dohme, Roche, and ViiV Healthcare. He has received research grants from Gilead, MSD Sharp & Dohme, RJanssen-Cilag and ViiV Healthcare. HJS received honoraria for consulting or speaking at educational events from Gilead, GlaxoSmithKline, Janssen-Cilag, MSD Sharp & Dohme. He has received trial documentation fees from AbbVie, Gilead Sciences, MSD Sharp & Dohme, Janssen-Cilag, GSK, and ViiV Healthcare. AS received honoraria for consulting and speaking at educational events as well as travel and research grants from AbbVie, Gilead, Janssen-Cilag, MSD Sharp & Dohme and ViiV. EW has received honoraria for consulting or speaking at educational events from AbbVie, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Hexal, Janssen-Cilag, MSD Sharp & Dohme, Roche, and ViiV Healthcare. EW is currently employee of MVZ Karlsplatz and MUC Research. MUC Research has received grants for clinical research from AbbVie, MSD Sharp & Dohme, Pfizer und ViiV Healthcare. CK is current employee of MUC Research GmbH.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The BESIDE study was initiated and funded by MSD Sharp & Dohme GmbH, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

ORCID iDs

B Funke

J Bruening

References

EMCDDA. Data and statistics: European drug data – prevalence of drug use. European Monitoring Centre for Drugs and Drug Addiction, www.emcdda.europa.eu/system/files/publications/12078/20192630_TD0319332ENN_PDF.pdf (2015, accessed 31 August 2020).

Garin

Velasco

De Pourcq

, et al. Corrigendum: Recreational drug use among individuals living with HIV in Europe: review of the prevalence, comparison with the general population and HIV guidelines recommendations. Front Microbiol 2015; 6: 1229.

Garin

Velasco

De Pourcq

, et al. Recreational drug use among individuals living with HIV in Europe: review of the prevalence, comparison with the general population and HIV guidelines recommendations. Front Microbiol 2015; 6: 690.

Hasse

Ledergerber

Furrer

, et al. Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study. Clin Infect Dis 2011; 53: 1130–1139.

Guaraldi

Orlando

Zona

, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis 2011; 53: 1120–1126.

Holtzman

Armon

Tedaldi

, et al. Polypharmacy and risk of antiretroviral drug interactions among the aging HIV-infected population. J Gen Intern Med 2013; 28: 1302–1310.

Kumar

Rao

Earla

, et al. Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems. Expert Opin Drug Metab Toxicol 2015; 11: 343–355.

King

Semlyen

Tai

, et al. A systematic review of mental disorder, suicide, and deliberate self harm in lesbian, gay and bisexual people. BMC Psychiatry 2008; 8: 70.

EMCDDA. Germany country drug report 2019, www.emcdda.europa.eu/system/files/publications/11334/germany-cdr-2019_0.pdf (2019, accessed 31 August 2020).

10.

Robert Koch Institute. Aktuelle Daten und Informationen zu Infektionskrankheiten und Public Health Epidemiologisches Bulletin. 2017. 47: 509–517.

11.

Robert Koch Institute. Aktuelle Daten und Informationen zu Infektionskrankheiten und Public Health. Epidemiologisches Bulletin, 2018; 47: 514–515.

12.

EMIS-Network. EMIS 2010: the European men-who-have-sex-with-men internet survey. Findings from 38 countries. Stockholm: European Centre for Disease Prevention and Control, 2013.

13.

EMIS (European Man-for-Man Internet Survey 2010). Final questionnaire, www.emis-project.eu/research-questions-and-covered-items.html (accessed 31 August 2020).

14.

Back D, Khoo S, Gibbons S, et al. The University of Liverpool, 1999–2020, https://www.hiv-druginteractions.org (accessed 6 July 2020).

15.

Atzendorf

Rauschert

Seitz

N-N

, et al. Gebrauch von Alkohol, Tabak, illegalen Drogen und Medikamenten. Deutsch Ärztebl Int 2019; 116: 577–584.

16.

Dirks

Esser

Borgmann

, et al. Substance use and sexual risk behaviour among HIV-positive men who have sex with men in specialized out-patient clinics. HIV Med 2012; 13: 533–540.

17.

Sewell

Cambiano

Miltz

, et al. Changes in recreational drug use, drug use associated with chemsex, and HIV-related behaviours, among HIV-negative men who have sex with men in London and Brighton, 2013–2016. Sex Transm Infect 2018; 94: 494–501.

18.

Daskalopoulou

Rodger

Phillips

, et al. Recreational drug use, polydrug use, and sexual behaviour in HIV-diagnosed men who have sex with men in the UK: results from the cross-sectional ASTRA study. Lancet HIV 2014; 1: e22–e31.

19.

Winstock

Mitcheson

New recreational drugs and the primary care approach to patients who use them. BMJ 2012; 344: e288.

20.

Ranjan

Kumari

Chakrawarty

How can doctors improve their communication skills?

J Clin Diagn Res 2015; 9: JE01–JE04.

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