Seventy-one percent of the total sample reported taking ART in the past 3 months, with significantly more heterosexual men reporting taking ARTs than MSM . Only 53% of the total sample presented an undetectable VL at baseline, with significantly more heterosexual men presenting an undetectable VL than MSM . The median CD4 + count at baseline was also significantly lower among heterosexual men than MSM . In both sites, heterosexual men were significantly older and had lower education than MSM. Figure 1 illustrates the type and pattern of non-injection substance use. In Thailand, of men who reported using non-injection substances in the past 3 months at baseline , 91% used one drug and 9% used two drugs simultaneously. In Thailand, among heterosexual men who reported using non-injection substances , 89% reported using one substance and 11% reported using two substances . In Thailand, among MSM who reported using non-injection substances , 94% reported using one substance and 6% reported using two substances . In Brazil, of men who reported using non-injection substances , 67% used one drug, 22% used two drugs, 5% used three drugs, and 2% used four drugs. In Brazil, among heterosexual men who reported using non-injection substances , 63% reported using one substance , 32% reported using two substances , and 5% reported using three substances . In Brazil, among MSM who reported using non-injection substances , 69% reported using one substance , 24% reported using two substances , 4% reported using three substances , and 6% reported using four substances . For MSM in Brazil, the proportion of ecstasy users increased with the number of substances an individual reported to have taken in the past 3 months.Table 2 reports the odds ratio of ART adherence ability or taking ARTs in the past 3 months and having an undetectable VL on non-injection substance use, adjusting for covariates such as age and education in the model. ART adherence ability or taking ARTs in the past 3 months was further adjusted in the VL analyses. In Thailand, plant grow table non-injection substance use was not significantly associated with ART adherence ability or undetectable VL in each risk group.
There were no differences between risk groups demonstrated by non-significant interaction terms. Furthermore, ART adherence did not mediate the association between substance use and undetectable VL. In Brazil, drug and alcohol misuse was associated with an overall lower likelihood of ART adherence ability and a lower likelihood of an undetectable VL, although this association was only significant in a few models. There were no differences between risk groups demonstrated by non-significant interaction terms. Furthermore, ART adherence did not mediate the association between substance use and undetectable VL. Alcohol misuse, although not significantly associated with having taken ARTs in the past 3 months, was significantly associated with decreased in odds of having an undetectable VL over 12 months in Brazilian MSM . Additionally, the number of non-injection substances used was significantly associated with decreased in odds of having taken ARTs in the past 3 months over 12 months in Brazilian heterosexual men . Table 3 reports the odds ratio of non-injection substance use on depressive symptoms and an undetectable VL using generalized linear mixed effects models. Depression was further adjusted in the undetectable VL analysis. In Thailand, non-injection substance use was associated with an overall greater likelihood of reporting severe depressive symptoms and lower likelihood of having an undetectable VL. Reporting alcohol misuse was significantly associated with an increase in reporting severe depressive symptoms in MSM . There were no differences between risk groups demonstrated by non-significant interaction terms. Severe depressive symptoms did not mediate the association between substance use and undetectable VL. In Brazil, non-injection substance use was generally not significantly associated with reporting depressive symptoms. Alcohol misuse, although not significantly associated with reporting severe depressive symptoms, was significantly associated with decreased odds of having an undetectable VL over 12 months in MSM . There were no differences between risk groups demonstrated by non-significant interaction terms. Severe depressive symptoms did not mediate the association between substance use and undetectable VL.This exploratory study examined the overlap between reported non-injection substance use, severity of depressive symptoms, ART adherence, and HIV VL undetectability among men living with HIV in Rio de Janeiro and Chiang Mai over 12 months. We found varying types and patterns of non-injection substance use between countries and sub-groups.
One key finding is that alcohol misuse, although not associated with reported ART adherence ability in Thailand or with taking ARTs in Brazil, was associated with significantly lower odds of achieving undetectable VL among MSM in Brazil. Another key finding is that the number of non-injection substances used was associated with lower odds of taking ARTs in the past 3 months among heterosexual men in Brazil, but not in Thailand. Lastly, alcohol misuse was associated with significantly greater odds of having depressive symptoms among MSM in Thailand, although not significantly associated with HIV VL. Reported alcohol misuse was prevalent in this sample and was associated with significantly lower odds of achieving an undetectable VL among MSM in Brazil. Alcohol misuse was detected in 35.2% and 47.3% in our of HIV-infected men. This high prevalence of alcohol misuse is consistent with one review documenting that alcohol use disorders can be up to two to four times more prevalent among PLH than the general population in U.S. populations. Factors that might explain lack of HIV suppression in our sample could range from biological factors to the diminished cognitive function and dysfunctional behaviors caused by alcohol misuse that may lead to poor self-regulation. Alcohol misuse might directly affect HIV control by inhibiting ART metabolism, enhancing HIV disease progression by lowering CD4+T-cell count, and/or increasing HIV replication in peripheral blood mononuclear cells. These biological mechanisms deserve further research in human subjects, as the current knowledge base is largely limited to animal models. Regardless of the mechanism, our findings support the rationale for investing resources into alcohol misuse screening and prevention interventions among men with HIV/AIDS in middle-income countries, such as Brazil and Thailand. Another key finding is that each additional substance used was associated with lower odds of taking ART among heterosexual men in Brazil. Poly substance use among heterosexual men in Brazil involved reporting a combination of alcohol misuse, powder cocaine use, and/or cannabis use. Substance use, powder cocaine in particular, has been previously associated with poor ART adherence ability and faster HIV disease progressio. specifically, cocaine may increase HIV disease progression by increasing HIV replication in PBMCs and increasing circulating HIV-1 RNA. There are fewer studies on the effect of cannabis on ART adherence ability and HIV VL with mixed findings. Interestingly, non-injection substance use was associated with decreased odds of taking ART only among heterosexual men in Brazil. Previous studies that examined non-injection substance use among individuals with HIV have primarily focused on MSM. As there is limited research on non-injection substance use and ART adherence among HIV infected heterosexual men, future research should examine this relationship to elucidate the contributing factors. Blips in HIV VL exams are also more frequent among people who misuse alcohol and drugs.
Additional studies of ART adherence with biomarkers would enhance the understanding of how poly substance use, ART, and HIV VL interact physiologically. Lastly, we found that alcohol misuse was associated with significantly greater odds of having depressive symptoms among MSM in Thailand. Although our study found that depressive symptoms were not significantly associated with undetectable HIV VL, depression severity is consistently associated with inconsistent ART adherence and discontinuation. Future research is needed to evaluate the efficacy of psychological and psychiatric interventions in mitigating the deleterious effects of substance use and depression on HIV disease progression. A recent critical literature review highlights some promising cognitive and behavioral and motivational interview interventions conducted among HIV infected substance using MSM in the US. Such interventions need to be adapted and evaluated in other countries and socio-cultural contexts. The current findings should be considered in light of several limitations and strengths. First, non-injection substance use and ART adherence ability were self reported and subject to potential biases based on recall bias or social desirability, the intentional under-reporting of sensitive or socially undesirable outcomes. There was likely under-reporting of alcohol misuse, non-injection drug use, and ART non-adherence. Future studies should include more comprehensive measurements of substance use and ART adherence. For example, physiological biomarkers of substance use and ART adherence provide a more objective measure of chronicity and extent of substance use. Likewise, future studies would benefit from using instruments that assess substance misuse , as the current study assessed the number of days of non-injection drug use rather than misuse. Second, under-reporting, small sample size, and truncated variability could have decreased our statistical power to detect a significant association between key variables like stimulants, cannabis, poly substance use, and HIV outcomes. Furthermore, it is important to highlight that significant associations were found in only one of the four sub-groups. Inconsistent findings could reflect distinct substance use and HIV care characteristics across countries and sub-groups,hydroponic table but could also be due to type 1 error. Third, our findings are not generalizable to populations of HIV-infected men in Thailand and in Brazil as this study focused on men engaged in care in select clinics and cities in each country. Despite these limitations, this study contributes to evidence that achieving an undetectable VL is possible among male, non-injection substance users in low- and middle- income countries.However, among MSM in Thailand and Brazil who misuse alcohol and among heterosexual men in Brazil who use multiple non-injection substances, interventions that address substance use may aim to lift mood, boost ART adherence and reduce HIV VL.Humans increasingly use e-cigarette devices filled with cannabis extracts to administer ∆9- tetrahydrocannabinol and other constituents . This has spurred development of pre-clinical models which are capable of a similar route of drug administration in laboratory rodents. Recent studies showed that intrapulmonary delivery of THC using an e-cigarette based system results in a dose-dependent hypothermia and anti-nociception in male and female rats ; a similar system produces hypothermia in mice after inhalation of synthetic cannabinoid agonists . Effects of cannabidiol and nicotine inhalation in combination with THC appear to produce independent effects and repeated inhalation of THC produces tolerance in adult rats .
Repeated adolescent inhalation of THC induces tolerance that lasts into early adulthood, and changes in motivated behavior . Most provocatively, a recent study appears to show evidence of THC self-administration via the inhalation route in rats . If confirmed, this has the potential to revolutionize study of the reinforcing properties of THC alone and in context of other exogenous cannabinoids. Recent discussion of replication and reliability across scientific disciplines identifies the generalization of effects, beyond narrowly constrained protocols, as a key issue. It may be the case that what appear to be minor variations from a published method are in fact important and the target effect do not generalize across such variations. It is therefore of significant interest with new methods to determine where methodological choices, e.g., rat strain, do or do not affect experimental outcomes. Such differences may be qualitative or quantitative . While our prior studies of cannabinoid inhalation have shown efficacy in both Wistar and Sprague-Dawley rats , the observed effects have not been directly compared across the strains. The major goal of this study was therefore to determine any strain differences using age- and treatment-matched male rats. Previous studies have reported some strain-related differences in the effects of THC. For example, adolescent THC exposure differentially affects adult measures of learning, with WI rats shown to be less sensitive than Long-Evans rats , and repeated adolescent THC injection resulted in different effects on heroin conditioned place preference in Fischer 344 versus Lewis rats . Strain differences are not always found in THC response, for example, there were no differences between Fischer and Lewis rat strains reported in a study of THC-induced conditioned taste avoidance and hypothermia . Apart from direct comparison studies such as these, it is difficult to compare across strains as a given laboratory will typically adopt a single rat strain , and fixed methodological parameters with respect to route of administration , dose ranges, types of assay . A substantial decrease in body temperature, and a decrease in nociceptive sensitivity, are major indicators of cannabinoid-like activity in laboratory rodents and are therefore ideal in vivo readouts for determining efficacy.