Naturally Derived Anti-HIV Polysaccharide Peptide (PSP) Triggers a Toll-Like Receptor 4-Dependent Antiviral Immune Response.

AIM: Intense interest remains in the identification of compounds to reduce human immunodeficiency virus type 1 (HIV-1) replication. Coriolus versicolor's polysaccharide peptide (PSP) has been demonstrated to possess immunomodulatory properties with the ability to activate an innate immune response through Toll-like receptor 4 (TLR4) showing insignificant toxicity. This study sought to determine the potential use of PSP as an anti-HIV agent and whether its antiviral immune response was TLR4 dependent. MATERIALS AND METHODS: HIV-1 p24 and anti-HIV chemokine release was assessed in HIV-positive (HIV+) THP1 cells and validated in HIV+ peripheral blood mononuclear cells (PBMCs), to determine PSP antiviral activity. The involvement of TLR4 activation in PSP anti-HIV activity was evaluated by inhibition. RESULTS: PSP showed a promising potential as an anti-HIV agent, by downregulating viral replication and promoting the upregulation of specific antiviral chemokines (RANTES, MIP-1α/ß, and SDF-1α) known to block HIV-1 coreceptors in THP1 cells and human PBMCs. PSP produced a 61% viral inhibition after PSP treatment in HIV-1-infected THP1 cells. Additionally, PSP upregulated the expression of TLR4 and TLR4 inhibition led to countereffects in chemokine expression and HIV-1 replication. CONCLUSION: Taken together, these findings put forward the first evidence that PSP exerts an anti-HIV activity mediated by TLR4 and key antiviral chemokines. Elucidating these new molecular mediators may reveal additional drug targets and open novel therapeutic avenues for HIV-1 infection.

A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011.

Puerto Rico has one of the highest rates of HIV/AIDS seen for any US state or territory, and antiretroviral therapy has been a mainstay of efforts to mitigate the HIV/AIDS public health burden on the island. We studied the evolutionary dynamics of HIV-1 mutation and antiretroviral drug resistance in Puerto Rico by monitoring the population frequency of resistance-associated mutations from 2002 to 2011. Whole blood samples from 4,475 patients were analyzed using the TRUGENE HIV-1 Genotyping Kit and OpenGene DNA Sequencing System in the Immunoretrovirus Research Laboratory at Universidad Central del Caribe. Results show that 64.0% of female and 62.9% of male patients had HIV-1 mutations that confer resistance to at least one antiretroviral medication. L63P and M184V were the dominant mutations observed for the protease (PRO) and reverse transcriptase (RT) encoding genes, respectively. Specific resistance mutations, along with their associated drug resistance profiles, can be seen to form temporal clusters that reveal a steadily changing landscape of resistance trends over time. Both women and men showed resistance mutations for an average of 4.8 drugs over the 10-year period, further underscoring the strong selective pressure exerted by antiretrovirals along with the rapid adaptive response of HIV. Nevertheless, both female and male patients showed a precipitous decrease for overall drug resistance, and for PRO mutations in particular, over the entire course of the study, with the most rapid decrease in frequency seen after 2006. The reduced HIV-1 mutation and drug resistance trends that we observed are consistent with previous reports from multi-year studies conducted around the world. Reduced resistance can be attributed to the use of more efficacious antiretroviral drug therapy, including the introduction of multi-drug combination therapies, which limited the ability of the virus to mount rapid adaptive responses to antiretroviral selection pressure.

Malignancies Trends in a Hispanic Cohort of HIV Persons in Puerto Rico before and after cART.

BACKGROUND: The study describes the cancer trends in a Puerto Rican Hispanic HIV/AIDS cohort for three different time periods as defined by the availability of combination antiretroviral therapy (cART) in the Island: pre (1992-1995), early (1996-2002, and recent (2003-2009). METHODS: AIDS and non-AIDS related malignancies risk, standardized incidence rate and one year mortality was evaluated in the cohort before and after cART. RESULTS: Of the 281 malignancies found in 265 persons; 72% were in men, 38% in injecting drug users and 42.3% were AIDS related cancers. AIDS related cancer standardized incidence rates decreased significantly in the cART eras; however, Kaposi's sarcoma and invasive cervical carcinoma incidence remained significantly higher in the cohort when compare to the general population. On the contrary, non-AIDS related cancer standardized incidence rates increased significantly in the cART eras, specifically those of the oral/cavity/pharynx, liver, anus, vaginal, and Hodgkin's and non-Hodgkin's Lymphomas. Around 50% of the persons with cancers were reported dead within the first year of their diagnoses without a significant variation during the cART eras. CONCLUSION: The higher incidence of Kaposi's sarcoma, invasive cervical carcinoma and non-AIDS related malignancies and their high mortality in the cART eras is suggestive of the role of oncogenic viruses, environmental agents, risky lifestyle behaviors and inadequate cancer prevention efforts that contribute and accelerate the risk of malignant transformation in these subjects. Aggressive intervention in the form of vaccines, risky practice reduction, early screening, early treatment and adequate risk reduction education needs to be incremented in this vulnerable population.

Persistent HIV Viremia: Description of a Cohort of HIV Infected Individuals with ART Failure in Puerto Rico.

The introduction of antiretroviral therapy (ART) has allowed human immunodeficiency virus (HIV) suppression in patients. We present data of a cohort of Puerto Rican patients with HIV who were under treatment with a steady regime of ART across a time horizon of eleven years. The time periods were categorized into four year stratums: 2000 to 2002; 2003 to 2005; 2006 to 2008 and 2009 to 2011. Socio-demographic profile, HIV risk factors, co-morbid conditions were included as study variables. One year mortality was defined. The p value was set at ≤0.05. The cohort consisted of 882 patients with 661 subjects presenting with persistent HIV viral load after a self-reported 12 month history of ART use. In this sub-cohort a higher viral load was seen across time (p < 0.05). Illicit drug use, IV drug use, alcohol use, loss of work were associated to having higher viral load means (p < 0.05). HIV viral load mean was lower as BMI increased (p < 0.001). It is imperative to readdress antiretroviral adherence protocols and further study ART tolerance and compliance.

Impact of ASUMA Intervention on HIV Risk Behaviors among Puerto Rican Adolescents.

The purpose of this manuscript is to assess and compare HIV risk behaviors among early adolescents after a three-year pilot study. A total of 135 public and private junior high schools students completed the intervention protocol. A self-administered questionnaire was given at baseline and at the end of the third year (fourth measure). Descriptive and inferential analyses were performed using SPSS 20.0. About 60% of the students were 14 years old at the fourth measure. The proportion of students that did not report at least one HIV risk behavior at baseline and those that reported any risk behavior at the fourth measure was lower in the intervention group (45.0%) than in the control group (54.5%). The proportion of students that reported at least one HIV risk behavior at baseline and those that did not report any HIV risk behavior at the fourth measure was higher in the intervention group than in the control group (33.3% vs. 8.3%). The proportion of students engaging in HIV risk behaviors was higher in the control group than in the intervention group at the fourth measure, suggesting that A Supportive Model for HIV Risk Reduction in Early Adolescence (ASUMA) intervention might be a promising initiative to reduce adolescents' engagement in HIV risk behaviors.

Chemical conjugation of 2-hexadecynoic acid to C5-curcumin enhances its antibacterial activity against multi-drug resistant bacteria.

The first total synthesis of a C5-curcumin-2-hexadecynoic acid (C5-Curc-2-HDA, 6) conjugate was successfully performed. Through a three-step synthetic route, conjugate 6 was obtained in 13% overall yield and tested for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. Our results revealed that 6 was active against eight MRSA strains at MICs that range between 31.3 and 62.5 µg/mL. It was found that the presence of 2-hexadecynoic acid (2-HDA, 4) in conjugate 6 increased 4-8-fold its antibacterial activity against MRSA strains supporting our hypothesis that the chemical connection of 4 to C5-curcumin (2) increases the antibacterial activity of 2 against Gram-positive bacteria. Combinational index (CIn) values that range between 1.6 and 2.3 were obtained when eight MRSA strains were treated with an equimolar mixture of 2 and 4. These results demonstrated that an antagonistic effect is taking place. Finally, it was investigated whether conjugate 6 can affect the replication process of S. aureus, since this compound inhibited the supercoiling activity of the S. aureus DNA gyrase at minimum inhibitory concentrations (MIC) of 250 µg/mL (IC50=100.2±13.9 µg/mL). Moreover, it was observed that the presence of 4 in conjugate 6 improves the anti-topoisomerase activity of 2 towards S. aureus DNA gyrase, which is in agreement with results obtained from antibacterial susceptibility tests involving MRSA strains.

Immunomodulator-based enhancement of anti smallpox immune responses.

BACKGROUND: The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. METHODS: We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. RESULTS: The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. CONCLUSION: These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

Synthesis of novel C5-curcuminoid-fatty acid conjugates and mechanistic investigation of their anticancer activity.

The first synthesis of C5-curcumin-fatty acid (C5-Curc-FA) conjugates was successfully performed. Through a two-step synthetic route, 10 analogs were synthesized for a structure-activity relationship (SAR) study. It was found that C5-Curc-FA conjugates containing either decanoic acid or palmitic acid moieties were cytotoxic against colorectal adenocarcinoma cell (CCL-229) at IC50s ranging from 22.5 to 56.1µg/mL, being 5c the most active C5-Curc-FA conjugate. Our results strongly suggests that a decanoic acid moiety at the meta position in C5-Curc-FA conjugates is important for their anticancer activity effect. Possible mechanisms for the anticancer activity of C5-Curc-FA conjugates were also investigated including apoptosis induction, mitochondrial damage and caspases activation. It was shown that 5c inhibited the luminescence activity of NFκB, a key signaling molecule involved in cell apoptosis and cell proliferation, at IC50=18.2µg/mL. In addition, it was demonstrated that 5c displayed significant apoptotic effect at GI50=46.0µg/mL in colorectal adenocarcinoma cell line (ATCC CCL-222), which can be explained by the significant mitochondrial membrane permeabilization and caspases 3 and 7 activation effect of 5c. Finally, it was investigated that C5-Curc-FA conjugates can affect the replication process of cancer cells, since compounds 5c, 5e, and 6c inhibited the relaxing activity of the human DNA topoisomerase I at minimum inhibitory concentrations (MICs) that range from 50 to 250µg/mL. Our results strongly support the hypothesis that the inhibition of both NFκB and DNA topoisomerase I by C5-Curc-FA conjugates is associated with their anticancer activity.

Antibacterial activity of 2-alkynoic fatty acids against multidrug-resistant bacteria.

The first study aimed at determining the structural characteristics needed to prepare antibacterial 2-alkynoic fatty acids (2-AFAs) was accomplished by synthesizing several 2-AFAs and other analogs in 18-76% overall yields. Among all the compounds tested, the 2-hexadecynoic acid (2-HDA) displayed the best overall antibacterial activity against Gram-positive Staphylococcus aureus (MIC=15.6 µg/mL), Staphylococcus saprophyticus (MIC=15.5 µg/mL), and Bacillus cereus (MIC=31.3 µg/mL), as well as against the Gram-negative Klebsiella pneumoniae (7.8 µg/mL) and Pseudomonas aeruginosa (MIC=125 µg/mL). In addition, 2-HDA displayed significant antibacterial activity against methicillin-resistant S. aureus (MRSA) ATCC 43300 (MIC=15.6 µg/mL) and clinical isolates of MRSA (MIC=3.9 µg/mL). No direct relationship was found between the antibacterial activity of 2-AFAs and their critical micelle concentration (CMC) suggesting that the antibacterial properties of these fatty acids are not mediated by micelle formation. It was demonstrated that the presence of a triple bond at C-2 and the carboxylic acid moiety in 2-AFAs are important for their antibacterial activity. 2-HDA has the potential to be further evaluated for use in antibacterial formulations.

Oral human papillomavirus infection among drug users in Puerto Rico.

OBJECTIVE: The prevalence of human papillomavirus (HPV) in the oral cavity has not been as well studied as genital infection and its prevalence among drug users is uncertain. This study describes the prevalence and correlates of oral HPV infection among a sample of drug users in Puerto Rico (PR). METHODS: Cross-sectional study of 271 drug users aged 18-35 years, not undergoing substance abuse treatment, living in the San Juan metropolitan area. Oral samples were collected through an oral rinse and HPV infection status was detected through PCR and HPV typing. Information on covariates was obtained through face-to-face interviews and serum analyses. RESULTS: A total of 34 participants were positive for any HPV type (12.5%), whereas 13 individuals (4.8%) were positive for one of the 38 type-specific HPV probes evaluated. Among those HPV positive, the most common HPV type detected was non-oncogenic HPV 72 (11.8%, n = 4). Oncogenic HPV types detected were 35 (5.9%) and 56 (2.9%). Factors associated with oral HPV infection included binge drinking (OR = 3.85, 95% CI = 1.40, 10.58), HIV positivity (OR = 4.67, 95% CI = 1.58, 13.74) and ever having engaged in commercial sex (OR = 3.55, 95% CI = 1.46, 8.67); infection did not differ by age or gender. CONCLUSION: Consistent with previous studies in the genital and oral tract, HIV infection, alcohol abuse and commercial sex practices were strongly associated with oral HPV infection. Future studies should assess the implications of oral HPV infection on oral cancer risk in this population.

HIV/AIDS in the Puerto Rican elderly: immunological changes between gender and body mass index.

PURPOSE: Human immunodeficiency virus (HIV) in the elderly population has serious repercussions. The elderly are underdiagnosed for HIV and the costs associated with their late-stage care represent a financial burden to the public health system. The purpose is to analyze various profiles among a cohort of elderly patients with HIV/AIDS. METHODS: This is a baseline cohort 60 years or older seen in the Retrovirus Research Center between January 2000 to December 2011. We present the profiles of our cohort stratified by gender and body mass index viewed as a covariate of interest. RESULTS: A total of 266 people (68% males and 32% females) seen at the Center were older than 60 years of age. Males were significantly more often overweight (p<.05). Females were significantly more underweight with chronic conditions (p<.05). Women had higher CD4 count and lower HIV viral loads (p<.05). Underweight elderly males were more heavily affected with the burden of HIV infection compared with women.

Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010.

This is a continuation of our efforts to maintain a record of the evolution of HIV-1 infection in Puerto Rico by monitoring the expression levels of antiretroviral drug-resistance-associated mutations. Samples from 2,500 patients from 2006-2010 were analyzed using the TruGene HIV-1 genotyping kit and the OpenGene DNA sequencing system. Results show that 58.8% of males and 65.3% of females had HIV-1 with resistance to at least one medication. The average number of HIV mutations was 6.0 in males and 6.1 in females. Statistically significant differences between men and women were recorded in the levels of HIV-1 expressed mutations and antiretroviral drug resistance. The most prevalent antiretroviral medication resistance shifted from zalcitabine to nevirapine and efavirenz in the five-year period. M184V and L63P were the dominant mutations for the reverse transcriptase and the protease genes, respectively, but an increase in the incidence of minority mutations was observed.

Toxoplasmic encephalitis in an AIDS cohort at Puerto Rico before and after highly active antiretroviral therapy (HAART).

Highly active antiretroviral therapy (HAART) significantly reduced the toxoplasmic encephalitis (TE) incidence in acquired immunodeficiency syndrome (AIDS) patients. The TE incidence and mortality were evaluated in an AIDS cohort followed in Puerto Rico before, during, and after HAART implementation in the Island. Of the 2,431 AIDS studied patients 10.9% had TE diagnosis, with an incidence density that decreased from 5.9/100 person-years to 1.1/100 person-years after HAART. Cox proportional hazard analysis showed substantial mortality reduction among TE cases who received HAART. No mortality reduction was seen in those cases who received TE prophylaxis. Although this study shows a TE incidence and mortality reduction in the AIDS cohort after HAART, the incidence was higher than those reported in the United States AIDS patients. Poor TE prophylaxis compliance might explain the lack of impact of this intervention. Strengthening the diagnostic and opportune TE diagnosis and prompt initiation of HAART in susceptible patients is important to control this opportunistic infection.

Implications of ER stress, the unfolded protein response, and pro- and anti-apoptotic protein fingerprints in human monocyte-derived dendritic cells treated with alcohol.

BACKGROUND: Dendritic cells (DCs) are responsible for the activation of T cells and B cells. There is accumulating evidence that psychoactive substances such as alcohol can affect immune responses. We hypothesize that this occurs by modulating changes in proteins triggering a process known as unfolded protein response (UPR). This process protects cells from the toxic effects of misfolded proteins responsible for causing endoplasmic reticulum (ER) stress. Although much is known about ER stress, little is understood about the consequences of ethanol use on DC's protein expression. METHODS: In this study, we investigated alterations in the proteins of human monocyte-derived dendritic cells (MDDC) treated with 0.1% of alcohol by two-dimensional (2D) gel electrophoresis followed by liquid chromatography-tandem mass spectrometry, protein identification, and confirmation at the gene expression level by qRT-PCR. RESULTS: Proteomes of related samples demonstrated 32 differentially expressed proteins that had a 2-fold or greater change in expression (18 spots were up-regulated and 14 were down-regulated), compared to the control cultures (untreated cells). Alcohol significantly changed the expression of several components of the UPR stress-induced pathways that include chaperones, ER stress, antioxidant enzymes, proteases, alcohol dehydrogenase, cytoskeletal and apoptosis-regulating proteins. qRT-PCR analyses highlighted the enhanced expression of UPR and antioxidant genes that increased (18 hours) with alcohol treatment. CONCLUSION: Results of these analyses provide insights into alcohol mechanisms of regulating DC and suggest that alcohol induced specifically the UPR in DC. We speculate that activation of a UPR by alcohol may protect the DC from oxidant injury but may lead to the development of alcohol-related diseases.

Changes in developmental factors and HIV risk behaviors among early adolescents in Puerto Rico.

INTRODUCTION: Teenagers are the fastest growing group of newly HIV-infected persons. Consequently, a support model for HIV risk reduction was designed and implemented for early adolescents in Puerto Rico. OBJECTIVE: The purpose of this article is to assess changes in developmental factors and HIV risk behaviors among early adolescents after three years of follow-up of an intervention and a non-intervention group. METHODS: This prospective cohort study followed 135 early adolescents who were enrolled in the ASUMA (A Supportive Model for HIV Risk Reduction in Early Adolescents) Project. The study was performed in two public and two private junior schools. Baseline and three follow-up self-administered questionnaires were given. We examined sociodemographic factors, HIV risk behavior and developmental factors. RESULTS: 48% were in the intervention group and 51.1% were controls. Most adolescents were aged 12 years; 47.4% were males; 75.6% reported not having risk behaviors and 24.4% reported having risk behaviors at anytime in their lifespan. A significant decrease in the HIV risk behaviors median was observed among the intervention group (P < .05), while a nonsignificant increase was found among adolescents in the control group. At the end of the implementation phase, positive improvement in the developmental factors were observed in the intervention group (P < .05). CONCLUSIONS: Our study suggests that the ASUMA project curriculum had a positive effect on developmental factors and HIV risk behaviors, as proposed in our conceptual framework. Also, this study illustrates the importance of the creation of culturally appropriate instruments and interventions to reach the goal of HIV/AIDS reduction.

The morbidity and mortality associated with kidney disease in an HIV-infected cohort in Puerto Rico.

INTRODUCTION: Nephropathy in HIV-infected patients has been associated with progression to AIDS and death. The virus, several comorbid conditions and certain medications may contribute to the development and progression of kidney disease. METHODS: This study analyzed data collected from HIV-infected persons enrolled in a HIV registry in Puerto Rico during January 1998 through September 2006. Demographic factors, clinical manifestations, laboratory findings at enrollment, and antiretroviral therapy (ART) prescriptions were compared between patients with and without kidney disease. Death status and cause of death by December 2006 were also evaluated and compared. RESULTS: The study included 1,283 subjects, 69.0% male, 39.7% injecting drug users, 19.5% hepatitis C infected, 6.5% with diabetes mellitus (DM-2), 11.6% had hypertension (HTN) and 9.0% had kidney disease. Patients with kidney disease had significantly higher (P < .05) HIV viral load mean (273,499 vs. 202,858 copies/mL), CD4 T-cell count < 200 (57.0% vs. 44.4%), underweight (22.9% vs. 10.9%), DM-2 (13.9% vs. 5.8%), HTN (27.8% vs 10.0%) and mortality (15.9 vs 5.7 deaths per 100 years of follow-up) than those without it. Cox proportional hazard analysis showed that patients with kidney disease had a higher mortality risk (2.1) after controlling for age, sex, HIV risk factor, ART prescription in the last year and HIV disease duration. CONCLUSIONS: This study demonstrated a substantial disparity in mortality for Puerto Rican HIV-infected patients with nephropathy. Kidney disease preventive strategies that include aggressive control of HIV-infection and chronic medical conditions, such as hypertension and diabetes, are recommend as an approach to reduce this health disparity.

Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005.

This is a continuation of our efforts to maintain a record of the evolution of HIV-1 infection in Puerto Rico by monitoring the expression levels of antiretroviral resistance-associated mutations. Samples from 2005 were analyzed (458: 270 males, 137 females, 51 anonymous), using the TRUGENE HIV-1 Genotyping Kit and the OpenGene DNA Sequencing System. Results show that 60.1% of males and 50.2% of females had HIV-1 with resistance to at least one medication. The average number of HIV mutations in males was 6.27, while the average number of HIV mutations in females was 5.49. The highest levels of resistance were to Zalcitabine, Lamivudine, and Stavudine. The reverse transcriptase mutations with the highest frequency of expression were M184V, K103N and D67N. Protease mutations with the highest rate of expression were L63P, M361 and L90M. Significant differences between men and women were recorded in the levels of HIV-1 expressed mutations and resistance.

Pilot trial of an intervention aimed at modifying drug preparation practices among injection drug users in Puerto Rico.

Injection drug users (IDUs) contaminate preparation materials with blood-borne pathogens by using syringes as measuring and dispensing devices. In collaboration with IDUs, we developed a preventive intervention consisting of four new preparation practices aimed at avoiding the use of syringes in the preparation, and reducing the contamination of the materials. This report describes the results of a pilot trial introducing the new practices to ascertain their adoption potential and their potential efficacy in reducing contamination. Participants comprised 37 active IDUs among whom the new practices were promoted during 16 weeks. In addition to self-reported behaviors, the study collected cookers and plastic caps from shooting galleries and tested them for the presence of blood residues. Adoption rates were: (1) cleaning of skin area with hand sanitizer--65.6%; (2) directly pouring water with a dropper into the cooker--56.3%; (3) drawing drug solution with a preparation syringe and syringe filter--34.4%; and, (4) backload rinsing syringes--53.1%. Rates of blood residues detected in cookers and plastic caps were 41.7% prior to the trial, 28.6% at week 8, 24.6% at week 14, and 12.0% at week 18. We believe the results of the pilot trial are compelling and suggest that this intervention merits further formal testing.

Profile of Puerto Rican HIV/AIDS patients with early and non-early initiation of injection drug use.

BACKGROUND: Early initiation of injection drug use (IDU) increases the risk of HIV infection. METHODS: We compare the sociodemographic, psychosocial, and clinical profiles of HIV-positive IDU patients according to the age at which IDU was initiated. This is a cross-sectional study of 1308 patients seen from 1992 through 2005. We compared the profile of patients with early (age < 13 years) vs non-early (age > 13 years) initiation of IDU. The Fisher and chi2 differences in proportions were performed to assess difference among study groups with earlier IDU. The Mantel-Haenszel test was used to calculate the odds ratio. The Kaplan-Meier and log rank tests were used to assess the median survival. Differences were considered significant at alpha = .05. RESULTS: Early initiation of IDU was reported in 11% of our sample. The early initiation group was more likely to smoke tobacco, use alcohol, attempt suicide, have a history of incarceration, have economic problems, and have episodes of anxiety, confusion, depression, excitation, impulsivity, and violence (P < .05). The general survival time of patients was 36.9 months (95% confidence interval 31.9-42.0). A higher prevalence of candidial esophagitis and Pneumocystis jirovecii pneumonia and a lower prevalence of hepatitis C virus coinfection were seen in the early initiation group (P < .05). No differences in mortality, use of antiretroviral therapy, or CD4 T-cell count were seen. CONCLUSIONS: Differences in terms of lifestyle, stress factors, and history of psychological events were seen in the group of patients with early initiation of IDU seen in our facilities. Differences in the clinical scenario were documented.