The Role of Substance Abuse in HIV Disease Progression: Reconciling Differences from Laboratory and Epidemiologic Investigations

Kapadia, Farzana; Vlahov, David; Donahoe, Robert M.; Friedland, Gerald

doi:10.1086/433175

Cited by 117 publications

(113 citation statements)

References 80 publications

Supporting

Mentioning

113

Contrasting

Order By: Relevance

“…However, HIV treatment regimens commonly consist of combinations of three and sometimes more drugs (8)(9)(10). In addition, drug abuse is a frequent comorbidity of HIV infection (26)(27)(28). Hence, the brains of many HIV patients are exposed to HIV-1, combinations of ARVs, and psychostimulants, such as METH, at the same time.…”

Section: Discussionmentioning

confidence: 99%

“…HIV infection is frequently associated with the use of recreational drugs, such as methamphetamine (METH) (26)(27)(28), and with a reduced adherence to ART regimens (29). METH abuse triggers behavioral symptoms, including agitation, anxiety, paranoia, psychosis, and aggression (26,27,30); a variety of cardiovas-cular problems (31,32); reactive microgliosis (33); and hyperthermia and convulsions (34).…”

mentioning

confidence: 99%

“…METH abuse triggers behavioral symptoms, including agitation, anxiety, paranoia, psychosis, and aggression (26,27,30); a variety of cardiovas-cular problems (31,32); reactive microgliosis (33); and hyperthermia and convulsions (34). METH users with HIV have also shown more neuronal injury and cognitive impairment due to HIV than individuals who do not abuse the drug (1,35).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

Sánchez

Varano

Rozieres

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

b HIV-1 infection frequently causes HIV-associated neurocognitive disorders (HAND) despite combination antiretroviral therapy (cART).Evidence is accumulating that components of cART can themselves be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine, seems to aggravate HAND and compromise antiretroviral therapy. However, the combined effect of virus and recreational and therapeutic drugs on the brain is poorly understood. Therefore, we exposed mixed neuronal-glial cerebrocortical cells to antiretrovirals (ARVs) (zidovudine [AZT], nevirapine [NVP], saquinavir [SQV], and 118-D-24) of four different pharmacological categories and to methamphetamine and, in some experiments, the HIV-1 gp120 protein for 24 h and 7 days. Subsequently, we assessed neuronal injury by fluorescence microscopy, using specific markers for neuronal dendrites and presynaptic terminals. We also analyzed the disturbance of neuronal ATP levels and assessed the involvement of autophagy by using immunofluorescence and Western blotting. ARVs caused alterations of neurites and presynaptic terminals primarily during the 7-day incubation and depending on the specific compounds and their combinations with and without methamphetamine. Similarly, the loss of neuronal ATP was context specific for each of the drugs or combinations thereof, with and without methamphetamine or viral gp120. Loss of ATP was associated with activation of AMP-activated protein kinase (AMPK) and autophagy, which, however, failed to restore normal levels of neuronal ATP. In contrast, boosting autophagy with rapamycin prevented the long-term drop of ATP during exposure to cART in combination with methamphetamine or gp120. Our findings indicate that the overall positive effect of cART on HIV infection is accompanied by detectable neurotoxicity, which in turn may be aggravated by methamphetamine.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

Sánchez

Varano

Rozieres

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Furthermore, in vitro and animal studies found immunosuppressive effects of opiates, cocaine and other illicit substances [24][25][26][27][28][29][30]. Since 1996, combination ART has largely determined the outcome of HIV infection in patients with access to care [16], and mortality was found to be substantially reduced after the introduction of potent ART also among IDUs [31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Uptake of and virological response to antiretroviral therapy among HIV‐infected former and current injecting drug users and persons in an opiate substitution treatment programme: the Swiss HIV Cohort Study

et al. 2009

View full text Add to dashboard Cite

ObjectivesThe aim of the study was to investigate the influence of continued injecting drug use, enrolment in an opiate substitution treatment programme (OSTP), or cessation of injecting drug use on the uptake and course of antiretroviral therapy (ART). DesignA prospective observational study of all participants in the Swiss HIV Cohort Study followed between 1997 and 2006 was carried out. MethodsWe distinguished four groups of former or current injecting drug users (IDUs): (i) abstinent former IDUs; (ii) persons in OSTPs without concomitant injecting drug use; (iii) persons in OSTPs with concomitant injecting drug use; (vi) current IDUs. These groups were compared with a group of patients who had never been IDUs. Factors related to ART uptake and virological endpoints were analysed using logistic generalized estimating equations. ResultsWe followed 8660 participants for 48 477 person-years; 29.7% were in the IDU HIV transmission group. The likelihood of being on ART at biannual visits was lower among individuals in OSTPs with concomitant injecting drug use [odds ratio (OR) 0.79; 95% confidence interval (CI) 0.71-0.89] and current IDUs (OR 0.80; 95% CI 0.67-0.96), compared with those who had never been IDUs (reference), abstinent former IDUs (OR 1.13; 95% CI 1.02-1.25) and individuals in OSTPs without injecting drug use (OR 1.18; 95% CI 1.06-1.31). The likelihood of suppressed viral replication on ART was similar among those who had never been IDUs, abstinent former IDUs and individuals in an OSTP without injecting drug use, and lower among those in OSTPs with concomitant drug use (OR 0.82; 95% CI 0.72-0.93) and current IDUs (OR 0.81; 0.65-1.00). Adherence to ART was decreased among persons with continued injecting drug use, and correlated with virological outcome. [4][5][6][7], the potential for interactions among medication, opiate substitution and illicit drugs [8], adverse effects [9], and limited access to [10,11], delayed use of [10,12,13], and decreased response to treatment [4,7]. As a consequence of such difficulties, physicians may be reluctant to offer ART to HIV-infected IDUs [14,15], resulting in less than optimal care and worse outcome [16,17].In HIV research, the term 'IDU' is commonly used to describe the HIV transmission category or patient characteristics. When investigating the course of HIV infection and the outcome of ART in these patients, however, it is an oversimplification to consider IDUs as a homogenous group. IDUs frequently change their drug injection behaviour, drug addiction treatment status or health care setting [18,19]. We aimed to investigate the influence of injecting drug use behaviour and enrolment in opiate substitution treatment programmes on the uptake of and virological response to ART among persons classified as belonging to the IDU HIV transmission group, and to study the association between injecting drug use behaviour and adherence to ART. We distinguished four distinct groups of former or current IDUs: (i) abstinent former IDUs who had completely stopped injecting d...

show abstract

“…However, our findings suggest that racial disparities in HIV/AIDS survival among Latinos are wider compared with racial disparities among the general HIV-positive population , Oramasionwu et al, 2009, Trepka et al, 2013b (Langford et al, 2007, Nogueras et al, 2006. Evidence suggests that the use of drugs might also accelerate the progression of HIV to AIDS (Cole et al, 2015) by weakening the immune system, interacting with antiretroviral medication, and increasing social barriers to treatment access and adherence (Kapadia et al, 2005).…”

Section: Discussionmentioning

confidence: 61%

Neighborhood-level Determinants of Delayed HIV Diagnosis and Survival among HIV-positive Latinos, Florida 2000-2011

Delgado¹

View full text Add to dashboard Cite

The Role of Substance Abuse in HIV Disease Progression: Reconciling Differences from Laboratory and Epidemiologic Investigations

Cited by 117 publications

References 80 publications

Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

Uptake of and virological response to antiretroviral therapy among HIV‐infected former and current injecting drug users and persons in an opiate substitution treatment programme: the Swiss HIV Cohort Study

Neighborhood-level Determinants of Delayed HIV Diagnosis and Survival among HIV-positive Latinos, Florida 2000-2011

Contact Info

Product

Resources

About