Prevalence, beliefs and impact of drug-drug interactions between antiretroviral therapy and illicit drugs among people living with HIV in Spain.

Drug use implies important challenges related to HIV management, particularly due to an increased risk of potential interactions between antiretroviral therapy (ART) and illicit drugs (pDDIs). This study analyses the prevalence and severity of pDDIs among people living with HIV (PLHIV). It also explores their awareness of pDDIs and their beliefs about the toxicity that they may cause, as well as the impact of pDDIs on selected health variables. We conducted an on-line cross-sectional survey across 33 Spanish hospitals and NGOs to collect demographics and clinical data. pDDIs were checked against the Interaction Checker developed by Liverpool University. The sample of the present study was composed of 694 PLHIV who used illicit drugs. They represented 49.5% of the 1,401 PLHIV that participated in the survey. After excluding 38 participants due to lack of information on their ART or illicit drug use, 335 (51.1%) participants consuming drugs presented with some potentially significant pDDIs between their ART and illicit drugs, with a mean of 2.1±1.7 (1-10) pDDIs per patient. The drugs most frequently involved in pDDIs were cocaine, cannabis, MDMA and nitrates ("poppers"). The prevalence of pDDIs across ART regimens was: protease inhibitors (41.7%); integrase inhibitor-boosted regimens (32.1%), and non-nucleoside reverse transcriptase inhibitors (26.3%). An awareness of pDDIs and beliefs about their potential toxicity correlated positively with intentional non-adherence (p<0.0001). Participants with pDDIs exhibited a higher prevalence of intentional non-adherence (2.19±1.04 vs. 1.93±0.94; p = 0.001). The presence of pDDIs was not associated with poorer results in the clinical variables analysed. A significant proportion of PLHIV who use drugs experience pDDIs, thereby requiring close monitoring. pDDIs should be considered in the clinical management of HIV patients. Adequate information about pDDIs and indicators about how to manage ART when PLHIV use drugs could improve ART non-adherence.

Recreational Drug Use in People Living with HIV in Spain: Factors Associated with Drug Use and the Impact on Clinical Outcomes.

We analysed the impact of recreational drug use (RDU) on different outcomes in people living with HIV (PLHIV). A multicentre retrospective cohort study was performed with two cohorts of PLHIV included: people using recreational drugs (PURD) vs. people not using recreational drugs (PNURD). Overall, 275 PLHIV were included. RDU was associated with men having sex with men (OR 4.14, 95% CI [1.14, 5.19]), previous sexually transmitted infections (OR 4.00, 95% CI [1.97, 8.13]), and current smoking (OR 2.74, 95% CI [1.44, 5.19]). While the CD4/CD8 ratio increased amongst PNURD during the follow-up year, it decreased amongst PURD (p = 0.050). PURD presented lower scores of self-reported and multi-interval antiretroviral adherence (p = 0.017, and p = 0.006, respectively), emotional well-being (p < 0.0001), and regular follow-up (p = 0.059), but paid more visits to the emergency unit (p = 0.046). RDU worsens clinical, immunological, and mental health outcomes amongst PLHIV.

RESUMEN: Analizamos el impacto del consumo de drogas recreativas sobre variables relacionadas con la salud en personas con VIH (PVIH). Estudio multicéntrico retrospectivo con dos cohortes de PVIH: consumidores de drogas recreativas (CDR) y no consumidores (NCDR). Se incluyeron 275 PVIH. El consumo de drogas recreativas se asoció al colectivo de hombres que mantienen sexo con hombres (OR 4.14, IC95% [1.14, 5.19]), a infecciones de transmisión sexual previas (OR = 4.00, IC95% [1.97, 8.13]) y a ser fumador (OR = 2.74, IC95% [1.44, 5.19]). El ratio CD4/CD8 aumentó entre los NCDR durante el año de seguimiento y disminuyó en los CDR (p = 0.050). Los CDR presentaron peor adherencia al tratamiento antiretroviral medida con dos métodos indirectos (p = 0.017 y p = 0.006, respectivamente), y bienestar emocional (p < 0.0001). Además, visitaron menos al especialista en enfermedades infecciosas (p = 0.059), y más a urgencias (p = 0.046). El consumo de drogas recreativas empeora los resultados clínicos y de salud mental entre las PVIH.

Drug use and antiretroviral therapy (ART) interactions: a qualitative study to explore the knowledge, beliefs, adherence, and quality of life of people living with HIV taking ART and illicit drugs.

BACKGROUND: To explore the use of illicit drugs by people living with HIV (PLHIV) taking antiretroviral therapy (ART) and their relationship with variables relevant to the management of HIV infection, such as knowledge and beliefs about drug-drug interactions (DDIs), ART adherence, quality of life (QoL), and use of health-care resources. METHODS: 21 PLHIV in Spain who concomitantly took illicit drugs and ART participated in this qualitative study. Eight experts collaborated in the design of the semi-structured interview guide which explored the following topics: illicit drug use, knowledge and beliefs about DDIs and their impact on ART adherence, the effects of using illicit drugs on health, QoL, and use of health-care resources. Four of those experts, who were PLHIV and members of the executive boards of non-government organizations (NGOs) from four Spanish regions, recruited the participants through their NGOs and carried out the face-to-face interviews. Content analysis of the qualitative data was conducted with the support of the MAXQDA 12 program. RESULTS: Participants were mainly men (85.7%) and only 14.3% of them were heterosexual. Content analysis showed that the most frequently consumed illicit drugs were poppers, cocaine, and cannabis. Participants were polydrug users and this was, in many cases, prior to HIV diagnosis. Most participants presented theoretical potential moderate DDIs that would require monitoring. More than three quarters of them were not aware of these DDIs. Participants reported interactive toxicity beliefs that lead to intentional nonadherence behaviors. In most cases (n = 17), the participant's doctor knew about their drug use, however only six of them had had an open dialogue with their physician about it. Illicit drug use led to some health-related problems, mainly sexually transmitted infections. A positive QoL's self-perception was found among several participants that used recreational illicit drugs. CONCLUSIONS: Adequate information about DDIs and clues about how to manage ART when PLHIV are using illicit drugs could reduce the negative effects of such interactions and improve ART adherence and QoL.

Assessing quality of life in people with HIV in Spain: psychometric testing of the Spanish version of WHOQOL-HIV-BREF.

BACKGROUND: The assessment of health-related quality of life (HRQoL) in people living with HIV (PLHIV) has become crucial to evidence-based practice. The goals of this study are to analyze the psychometric properties and evidence of the validity of the Spanish version of WHOQOL-HIV-BREF in a sample of PLHIV in Spain and to examine the more impaired HRQoL facets and dimensions and identify the PLHIV who show the most vulnerable profile. METHODS: A total of 1462 PLHIV participated in an observational cross-sectional ex-post-facto study. Data were collected at 33 Spanish sites through an online survey. In addition to measuring HRQoL, the study used other tools to measure treatment adherence (CEAT-VIH 2.0 version), psychological well-being (GHQ-12) and HIV-related stigma (HSSS). Cronbach's alpha, first- and second-order confirmatory factor analysis (CFA), the Pearson coefficient and one-way ANOVA were used to evaluate reliability, construct validity and concurrent and known-group validity, respectively. Differences according to the socio-demographic and epidemiological profiles of participants were analyzed. RESULTS: First- and second-order CFAs confirmed a six-domain first-order structure of the Spanish version of WHOQOL-HIV-BREF and one second-order factor related to overall HRQoL with an acceptable fit to the data, although some minor changes would improve it. The six-domain structure showed an acceptable internal consistency (Cronbach's alpha ranged from .61 to .81). Significant moderate to large correlations between domains and overall HRQoL, adherence, psychological well-being and negative self-image were found. Significant differences were found according to participants' self-reported CD4+ cell count in several HRQoL facets and domains. Being female, heterosexual, having low socio-economic and educational statuses, having acquired HIV through an unsafe injection and living more years with HIV were related to poorer HRQoL. PLHIV older than 50 presented lower scores in 19 HRQoL facets. CONCLUSIONS: This study demonstrates that the Spanish version of the WHOQOL-HIV-BREF is a valid instrument. It also presents the most recent data about HRQoL in PLHIV in Spain with the largest sample to date.

Prevalence and patterns of illicit drug use in people living with HIV in Spain: A cross-sectional study.

This study assessed the prevalence and patterns of drug use among people living with HIV (PLHIV) in Spain. We conducted an observational cross-sectional study including 1401 PLHIV. Data were collected through 33 sites across Spain using an online computer-assisted self-administered interview. The survey measured use of illicit drugs and other substances, treatment adherence and health-related variables. To analyse patterns of drug use we performed cluster analysis in two stages. The most frequently consumed substances were: alcohol (86.7%), tobacco (55.0%), illicit drugs (49.5%), other substances (27.1%). The most prevalent illicit drugs used were cannabis (73.8%), cocaine powder (53.9%), and poppers (45.4%). Results found four clusters of PLHIV who used drugs. Two of them were composed mainly of heterosexuals (HTX): Cluster 1 (n = 172) presented the lowest polydrug use and they were mainly users of cannabis, and Cluster 2 (n = 84) grouped mostly men who used mainly heroin and cocaine; which had the highest percentage of people who inject drugs and presented the lowest level of treatment adherence (79.8±14.2; p < .0001). The other two clusters were composed mainly of men who have sex with men (MSM), who were mostly users of recreational drugs. Cluster 3 (n = 285) reported moderate consumption, both regarding frequency and diversity of drugs used, while Cluster 4 (n = 153) was characterized by the highest drug polyconsumption (7.4±2.2; p < .0001), and 4 grouped MSM who injected recreational drugs, and who reported the highest frequency of use of drugs in a sexual context (2.6±0.8; p < .0001) and rates of sexually transmitted infections (1.8±1.1; p < .01). This is the largest multi-centre cross-sectional study assessing the current prevalence and patterns of drug use among PLHIV in Spain. The highest prevalence of drug use was found among MSM, although HTX who used heroin and cocaine (Cluster 2) had the most problems with adherence to HIV treatment and the worst health status.

Oral Immunogenicity in Mice and Sows of Enterotoxigenic Escherichia Coli Outer-Membrane Vesicles Incorporated into Zein-Based Nanoparticles.

Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in neonatal and recently weaned pigs. The immune protection of the piglets derives from maternal colostrum, since this species does not receive maternal antibodies through the placenta. In the present study, outer membrane vesicles (OMVs) obtained from main ETEC strains involved in piglet infection (F4 and F18 serotypes), encapsulated into zein nanoparticles coated with Gantrez®® AN-mannosamine conjugate, were used to orally immunize mice and pregnant sows. Loaded nanoparticles were homogeneous and spherical in a shape, with a size of 220-280 nm. The diffusion of nanoparticles through porcine intestinal mucus barrier was assessed by a Multiple Particle Tracking technique, showing that these particles were able to diffuse efficiently (1.3% diffusion coefficient), validating their oral use. BALB/c mice were either orally immunized with free OMVs or encapsulated into nanoparticles (100 µg OMVs/mouse). Results indicated that a single dose of loaded nanoparticles was able to elicit higher levels of serum specific IgG1, IgG2a and IgA, as well as intestinal IgA, with respect to the free antigens. In addition, nanoparticles induced an increase in levels of IL-2, IL-4 and IFN-γ with respect to the administration of free OMVs. Orally immunized pregnant sows with the same formulation elicited colostrum-, serum- (IgG, IgA or IgM) and fecal- (IgA) specific antibodies and, what is most relevant, offspring suckling piglets presented specific IgG in serum. Further studies are needed to determine the infection protective capacity of this new oral subunit vaccine.

Microbiology of bacteria causing recurrent acute otitis media (AOM) and AOM treatment failure in young children in Spain: shifting pathogens in the post-pneumococcal conjugate vaccination era.

OBJECTIVE: To prospectively identify the bacterial aetiology and antimicrobial susceptibility of problematic (recurrent and treatment failure) acute otitis media in Spanish children several years after the introduction of 7-valent pneumococcal conjugate vaccine. METHODS: Tympanocentesis or careful sampling of spontaneous otorrhoea was performed on children aged 3 to <36 months with recurrent acute otitis media, acute otitis media treatment failure or unresolved acute otitis media. RESULTS: 105 acute otitis media episodes (77 sampled by tympanocentesis, 28 otorrhoea samples) were evaluated: 46 recurrent, 35 treatment failures, 24 unresolved acute otitis media. 74 episodes (70.4%) had at least one bacterium identified on culture: Streptococcus pneumoniae was identified in 21 episodes, Haemophilus influenzae (all non-typeable) in 44, Streptococcus pyogenes in 2, Moraxella catarrhalis in 2. No statistically significant difference in bacterial aetiology by episode type was detected. Non-typeable H. influenzae was the most commonly isolated pathogen in all acute otitis media types and in all age sub-groups. Forty percent of S. pneumoniae isolates were multi-drug resistant. Pneumococcal serotype 19A was the most frequently identified serotype (7/21 episodes). Multi-drug resistance was found in 56% of 19A isolates. Of non-typeable H. influenzae isolates, 15% were ampicillin resistant and 13% were amoxicillin/clavulanate resistant. S. pneumoniae and non-typeable H. influenzae DNA were each detected in 57% of samples culture negative for these pathogens, including 12 co-infections. CONCLUSION: Combining culture and polymerase chain reaction results, H. influenzae and S. pneumoniae may be implicated in 70% and 43% of clinically problematic bacterial acute otitis media episodes, respectively. The impact of new vaccines to prevent both S. pneumoniae and non-typeable H. influenzae acute otitis media may be substantial in this population and is worth investigating.