Cytokine/chemokine expression associated with Human Pegivirus (HPgV) infection in women with HIV.

A beneficial impact of the Human Pegivirus (HPgV)-formerly called GB virus C (GBV-C)-on HIV disease progression has been reported previously. One possible mechanism by which HPgV inhibits HIV replication is an alteration of the cytokine/chemokine milieu. Their expression has not been specifically evaluated in women despite their influence on disease progression and the possibility of gender-based differences in expression. Moreover, the impact of HPgV genotype on cytokine/chemokine expression is unknown. Sera levels of IL-2, IL-4, IL-7, IL-8, IL-10, IL-12p70, IL-13, IFNγ, TNFα, IP-10, MIP-1α, MIP-1ß, and TGF-ß1 were quantified in 150 HIV-positive women based on HPgV RNA status. Cytokines/chemokines with detection rates of at least 50% included IL-2, IL-4, IL-8, IL-10, IL-12p70, IFNγ, TNFα, IP-10, MIP-1α, MIP-1ß, and TGF-ß1 . Absolute values were significantly higher for HPgV positive compared to HPgV negative women for IL-7, IL-13, IL-12p70, and IFNγ. Absolute values were significantly lower for HPgV positive women for IL-4, IL-8, TGF-ß1 , and IP-10. IFNγ values were higher for HPgV genotype 2 than for genotype 1 (P = 0.036). Further study of cytokine/chemokine regulation by HPgV may ultimately lead to the development of novel therapeutic agents to treat HIV infection and/or the design of vaccine strategies that mimic the "protective" effects of HPgV replication.

HIV mono-infection is associated with FIB-4 - A noninvasive index of liver fibrosis - in women.

BACKGROUND: FIB-4 represents a noninvasive, composite index that is a validated measure of hepatic fibrosis, which is an important indicator of liver disease. To date, there are limited data regarding hepatic fibrosis in women. METHODS: FIB-4 was evaluated in a cohort of 1227 women, and associations were evaluated in univariate and multivariate regression models among 4 groups of subjects classified by their human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection status. RESULTS: The median FIB-4 scores were 0.60 in HIV-/HCV- women, 0.83 in HIV-/HCV+ women, 0.86 in HIV+/HCV- women, and 1.30 in HIV+/HCV+ women. In the HIV/HCV co-infected group, multivariate analysis showed that CD4(+) cell count and albumin level were negatively associated with FIB-4 (P <.0001), whereas antiretroviral therapy (ART) was positively associated with FIB-4 score (P =.0008). For the HIV mono-infected group, multivariate analysis showed that CD4(+) cell count (P <.0001) and albumin level (P =.0019) were negatively correlated with FIB-4 score, ART was positively associated with FIB-4 score (P =.0008), and plasma HIV RNA level was marginally associated with FIB-4 score (P =.080). In 72 HIV mono-infected women who were also hepatitis B surface antigen negative, ART naive, and reported no recent alcohol intake, plasma HIV RNA level was associated with increased FIB-4 score (P =.030). CONCLUSIONS: HIV RNA level was associated with increased FIB-4 score in the absence of hepatitis B, hepatitis C, ART, or alcohol use, suggesting a potential relationship between HIV infection and hepatic fibrosis in vivo. A better understanding of the various demographic and virologic variables that contribute to hepatic fibrosis may lead to more effective treatment of HIV infection and its co-morbid conditions.

Lack of association of herpes simplex virus type 2 seropositivity with the progression of HIV infection in the HERS cohort.

Many studies have chronicled the "epidemiologic synergy" between human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2). HIV adversely affects the natural history of HSV-2 and results in more frequent and severe HSV-2 reactivation. Few longitudinal studies, however, have examined whether HSV-2 is associated with increased HIV plasma viral loads or decreased CD4 counts. The authors estimated the effect of HSV-2 seropositivity on HIV RNA viral load and on CD4 count over time among 777 HIV-seropositive US women not receiving suppressive HSV-2 therapy in the HIV Epidemiology Research Study (1993-2000). Linear mixed models were used to assess the effect of HSV-2 on log HIV viral load and CD4 count/mm(3) prior to widespread initiation of highly active antiretroviral therapy. Coinfection with HSV-2 was not associated with HIV RNA plasma viral loads during study follow-up. There was a statistically significant association between HSV-2 seropositivity and CD4 count over time, but this difference was small and counterintuitive at an increase of 8 cells/mm(3) (95% confidence interval: 2, 14) per year among HSV-2-seropositive women compared with HSV-2-seronegative women. These data do not support a clinically meaningful effect of baseline HSV-2 seropositivity on the trajectories of HIV plasma viral loads or CD4 counts.

Human leukocyte antigen class I supertypes and HIV-1 control in African Americans.

The role of human leukocyte antigen (HLA) class I supertypes in controlling human immunodeficiency virus type 1 (HIV-1) infection in African Americans has not been established. We examined the effects of the HLA-A and HLA-B alleles and supertypes on the outcomes of HIV-1 clade B infection among 338 African American women and adolescents. HLA-B58 and -B62 supertypes (B58s and B62s) were associated with favorable HIV-1 disease control (proportional odds ratio [POR] of 0.33 and 95% confidence interval [95% CI] of 0.21 to 0.52 for the former and POR of 0.26 and 95% CI of 0.09 to 0.73 for the latter); B7s and B44s were associated with unfavorable disease control (POR of 2.39 and 95% CI of 1.54 to 3.73 for the former and POR of 1.63 and 95% CI of 1.08 to 2.47 for the latter). In general, individual alleles within specific B supertypes exerted relatively homogeneous effects. A notable exception was B27s, whose protective influence (POR, 0.58; 95% CI, 0.35 to 0.94) was masked by the opposing effect of its member allele B*1510. The associations of most B supertypes (e.g., B58s and B7s) were largely explained either by well-known effects of constituent B alleles or by effects of previously unimplicated B alleles aggregated into a particular supertype (e.g., B44s and B62s). A higher frequency of HLA-B genotypic supertypes correlated with a higher mean viral load (VL) and lower mean CD4 count (Pearson's r = 0.63 and 0.62, respectively; P = 0.03). Among the genotypic supertypes, B58s and its member allele B*57 contributed disproportionately to the explainable VL variation. The study demonstrated the dominant role of HLA-B supertypes in HIV-1 clade B-infected African Americans and further dissected the contributions of individual class I alleles and their population frequencies to the supertype effects.

The association between Trichomonas infection and incarceration in HIV-seropositive and at-risk HIV-seronegative women.

BACKGROUND: The prevalence of Trichomonas vaginalis is higher among incarcerated women than in the general community. We sought to determine whether a history of incarceration itself was independently associated with trichomoniasis. METHODS: The HIV Epidemiology Research Study is a prospective cohort study of 871 HIV-seropositive and 439 high-risk seronegative women in 4 urban centers (Bronx, NY; Detroit, MI; Providence, RI; Baltimore, MD). All participants enrolled between April 1993 and January 1995, with interviews and physical examinations conducted at baseline and at follow-up visits every 6 months up to 7 years. RESULTS: Of 1310 subjects, 427 (33%) reported being incarcerated on at least one occasion. In addition, 724 (55%) were found to have a sexually transmitted infection on at least one occasion during the study; baseline rates were 21% for T. vaginalis, 4.3% for Chlamydia trachomatis, 0.6% for N. gonorrhea, and 8% for syphilis. Incarceration was associated with the detection of trichomonas infection (between-subject, odds ratio, 2.4; 95% confidence interval: 1.85-3.14; P < 0.01 and within-subject, odds ratio, 1.56; 95% confidence interval: 1.26-1.92; P < 0.01). The association with incarceration remained significant after adjusting for age, race, HIV status, enrollment risk group, number of sexual partners, marital status, education, bacterial vaginosis, vaginal candidiasis, drug use (crack, cocaine, heroin), alcohol use, health insurance, receipt of public assistance, employment status, visit number, and study site. CONCLUSIONS: A history of incarceration was independently associated with the detection of trichomonas infection in a cohort of high-risk women. These data have implications for increased sexually transmitted infection prevention, screening, and treatment upon entry to jail as well as in the communities most affected by incarceration.

Accuracy of clinical diagnosis of bacterial vaginosis by human immunodeficiency virus infection status.

OBJECTIVE: To assess the accuracy of clinical diagnosis of bacterial vaginosis (BV) by using Amsel criteria, overall and by human immunodeficiency virus (HIV) infection status. METHODS: Women with HIV, or at risk for HIV, participated in the HIV Epidemiology Research Study, a prospective study conducted in 4 US sites. At enrollment and follow-up visits, scheduled at 6-month intervals for ≤ 5 years, participants received gynecologic examinations, had specimens collected, and underwent standardized interviews. We used McNemar test statistic to evaluate agreement between Amsel criteria and Nugent scoring. Using Nugent scoring as the reference standard, we calculated sensitivity and specificity for Amsel criteria and for 3 other classifications of clinical BV. Our results are based on data collected from 9140 study visits by 862 HIV-infected women and 421 HIV-uninfected women. RESULTS: Amsel criteria and Nugent scoring did not agree in the classification of BV cases (P < 0.01). Amsel criteria had poor sensitivity (60%; 95% confidence interval, 58%-61%) and specificity (90%; 95% confidence interval, 89%-91%) with wide differences in test properties by study site. We found no differences in diagnosing BV by HIV infection status. CONCLUSIONS: The under- and overdiagnosing of BV clinically suggests that the accuracy of Amsel criteria for routine screening of asymptomatic women might be lower than previous estimates; that clinicians need more rigorous training to apply subjective Amsel criteria accurately; or that wide heterogeneity in cases might prevent agreement between clinical and laboratory diagnoses, with future research needed to better understand the criteria or morphotypes associated with specific adverse outcomes.

Bacterial vaginosis and the natural history of human papillomavirus.

OBJECTIVE: To evaluate associations between common vaginal infections and human papillomavirus (HPV). STUDY DESIGN: Data from up to 15 visits on 756 HIV-infected women and 380 high-risk HIV-uninfected women enrolled in the HIV Epidemiology Research Study (HERS) were evaluated for associations of bacterial vaginosis, trichomoniasis, and vaginal Candida colonization with prevalent HPV, incident HPV, and clearance of HPV in multivariate analysis. RESULTS: Bacterial vaginosis (BV) was associated with increased odds for prevalent (aOR = 1.14, 95% CI: 1.04, 1.26) and incident (aOR = 1.24, 95% CI: 1.04, 1.47) HPV and with delayed clearance of infection (aHR = 0.84, 95% CI: 0.72, 0.97). Whereas BV at the preceding or current visit was associated with incident HPV, in an alternate model for the outcome of incident BV, HPV at the current, but not preceding, visit was associated with incident BV. CONCLUSION: These findings underscore the importance of prevention and successful treatment of bacterial vaginosis.

Association between semen exposure and incident bacterial vaginosis.

OBJECTIVE. To identify correlates of incident bacterial vaginosis (BV) diagnosed with Nugent scoring among high-risk women. STUDY DESIGN. We conducted both cohort and case-crossover analyses, stratified by HIV infection status, based on 871 HIV-infected and 439 HIV-uninfected participants in the HIV Epidemiology Research Study, conducted in 4 US sites in 1993-2000. RESULTS. BV incidence was 21% and 19% among HIV-infected and -uninfected women, respectively. Fewer correlates of BV were found with case-crossover than with cohort design. Reporting frequent coitus (regardless of consistency of condom use) was correlated with BV in cohort analyses but not in case-crossover analyses. The sole correlate of BV in both types of analyses was the detection of spermatozoa on Gram stain, which is a marker of semen exposure. CONCLUSION. The inconsistent association between condom use and BV in prior studies could be from reporting bias. We found evidence of a relationship between semen exposure and incident BV.

Trends related to aging and co-occurring disorders in HIV-infected drug users.

Drug users with HIV infection successfully treated with highly active antiretroviral therapy are now living to older ages. As persons with HIV infection age, they become at risk for comorbidities that occur in any group of aging individuals. However, some of these conditions occur at increased rates, with increasing severity, or pose special problems in older persons with HIV infection. This article discusses the epidemiology of HIV infection in aging drug users, and hormonal, cardiovascular, liver, renal, bone, and cognitive disorders and depression and cancer in these individuals, as well as problems related to taking multiple medications and HIV disease progression.

Protozoan-Viral-Bacterial Co-Infections Alter Galectin Levels and Associated Immunity Mediators in the Female Genital Tract.

Co-infections with sexually transmittable pathogens are common and more likely in women with disturbed vaginal bacteriome. Among those pathogens, the protozoan parasite Trichomonas vaginalis (TV) is most common after accounting for the highly persistent DNA viruses human papillomavirus (HPV) and genital herpes. The parasitic infection often concurs with the dysbiotic syndrome diagnosed as bacterial vaginosis (BV) and both are associated with risks of superimposed viral infections. Yet, the mechanisms of microbial synergisms in evading host immunity remain elusive. We present clinical and experimental evidence for a new role of galectins, glycan-sensing family of proteins, in mixed infections. We assessed participants of the HIV Epidemiology Research Study (HERS) at each of their incident TV visits (223 case visits) matched to controls who remained TV-negative throughout the study. Matching criteria included age, race, BV (by Nugent score), HIV status, hysterectomy, and contraceptive use. Non-matched variables included BV status at 6 months before the matched visit, and variables examined at baseline, within 6 months of and/or at the matched visit e.g. HSV-2, HPV, and relevant laboratory and socio-demographic parameters. Conditional logistic regression models using generalized estimating equations calculated odds ratios (OR) for incident TV occurrence with each log10 unit higher cervicovaginal concentration of galectins and cytokines. Incident TV was associated with higher levels of galectin-1, galectin-9, IL-1ß and chemokines (ORs 1.53 to 2.91, p <0.001). Galectin-9, IL-1ß and chemokines were up and galectin-3 down in TV cases with BV or intermediate Nugent versus normal Nugent scores (p <0.001). Galectin-9, IL-1ß and chemokines were up in TV-HIV and down in TV-HPV co-infections. In-vitro, TV synergized with its endosymbiont Trichomonasvirus (TVV) and BV bacteria to upregulate galectin-1, galectin-9, and inflammatory cytokines. The BV-bacterium Prevotella bivia alone and together with TV downregulated galectin-3 and synergistically upregulated galectin-1, galectin-9 and IL-1ß, mirroring the clinical findings of mixed TV-BV infections. P. bivia also downregulated TVV+TV-induced anti-viral response e.g. IP-10 and RANTES, providing a mechanism for conducing viral persistence in TV-BV co-infections. Collectively, the experimental and clinical data suggest that galectin-mediated immunity may be dysregulated and exploited by viral-protozoan-bacterial synergisms exacerbating inflammatory complications from dysbiosis and sexually transmitted infections.

Diversity of the hepatitis C virus NS5B gene during HIV co-infection.

Viral diversity is an important feature of hepatitis C virus (HCV) infection and an important predictor of disease progression and treatment response. HIV/HCV co-infection is associated with enhanced HCV replication, increased fibrosis, and the development of liver disease. HIV also increases quasispecies diversity of HCV structural genes, although limited data are available regarding the impact of HIV on non-structural genes of HCV, particularly in the absence of direct-acting therapies. The genetic diversity and presence of drug resistance mutations within the RNA-dependent RNA polymerase (NS5B) gene were examined in 3 groups of women with HCV genotype 1a infection, including those with HCV mono-infection, antiretroviral (ART)-naïve women with HIV/HCV co-infection and CD4 cell count <350 cells/mm3, and ART-naïve women with HIV/HCV co-infection and CD4 cell count ≥350 cells/mm3. None had ever been treated for HCV infection. There was evidence of significant diversity across the entire NS5B gene in all women. There were several nucleotides and amino acids with distinct distributions across the three study groups, although no obvious clustering of NS5B sequences was observed based on HIV co-infection or CD4 cell count. Polymorphisms at amino acid positions associated with resistance to dasabuvir and sofosbuvir were limited, although the Q309R variant associated with ribavirin resistance was present in 12 individuals with HCV mono-infection, 8 HIV/HCV co-infected individuals with CD4 <350 cells/mm3, and 12 HIV/HCV co-infected individuals with CD4 ≥350 cells/mm3. Previously reported fitness altering mutations were rare. CD8+ T cell responses against the human leukocyte antigen (HLA) B57-restricted epitopes NS5B2629-2637 and NS5B2936-2944 are critical for HCV control and were completely conserved in 44 (51.8%) and 70 (82.4%) study participants. These data demonstrate extensive variation across the NS5B gene. Genotypic variation may have a profound impact on HCV replication and pathogenesis and deserves careful evaluation.

The effect of highly active antiretroviral therapy on human papillomavirus clearance and cervical cytology.

OBJECTIVE: To examine the association of highly active antiretroviral therapy (HAART) with human papillomavirus (HPV) clearance and progression or regression of cervical cytological abnormalities in women with human immunodeficiency virus (HIV). METHODS: Five hundred thirty-seven women with HIV participating in the HIV Epidemiology Research Study, an observational, multisite cohort study, were evaluated semiannually from 1996 to 2000. Cervical Pap tests were collected for cervical cytology. Testing for HPV was conducted by polymerase chain reaction. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals (CIs). Number needed to treat (NNT) at 2 years was calculated for HAART. RESULTS: Among women with cervical squamous intraepithelial lesions, HAART was associated with an increased likelihood of HPV clearance (hazard ratio 4.5, 95% CI 1.2-16.3, NNT 22.4). Use of HAART was not associated with an increased likelihood of HPV clearance among women with normal cervical cytology (hazard ratio 1.7, 95% CI 0.9-3.1, NNT 6.5) or atypical squamous cells of undetermined significance cytology (hazard ratio 1.0, 95% CI 0.4-2.5, NNT 174.0). Use of HAART was not significantly associated with an increased likelihood of cervical cytologic regression (hazard ratio 1.3, 95% CI 1.0-1.7, NNT 10.9) or cervical cytologic progression (hazard ratio 0.7, 95% CI 0.6-1.0, NNT 12.8). CONCLUSION: Among women with preexisting abnormal cervical cytology, HAART was associated with enhanced HPV clearance but not with Pap test regression. Close monitoring of women with HIV for cervical cytologic abnormalities, regardless of HAART treatment status, is warranted. LEVEL OF EVIDENCE: II.

Hepatitis C virus infection is associated with insulin resistance among older adults with or at risk of HIV infection.

OBJECTIVES: To determine the associations of hepatitis C virus (HCV) infection with insulin resistance and abnormal glucose tolerance in a cohort of older adults with or at risk of HIV infection. DESIGN: A cross-sectional study of 267 HIV-infected and 179 at-risk-uninfected adults without a history of diabetes mellitus. METHODS: HCV antibody assays and RNA levels were performed to assess HCV status. Antiretroviral use, family history of diabetes, sedentary behavior, and sociodemographic data were obtained using standardized interviews. Fasting insulin levels and oral glucose tolerance tests were performed to assess two outcomes, the homeostasis model assessment of insulin resistance and abnormal glucose tolerance [impaired glucose tolerance (IGT) or diabetes]. RESULTS: Of 446 participants, 265 (59%) were HCV seropositive; of these, 199 (75%) had detectable HCV-RNA levels. Insulin resistance was greater among HCV-seropositive compared with seronegative participants, adjusting for body mass index, Hispanic ethnicity, age greater than 55 years, sedentary behavior (watching television > 4 h/day), HIV status, HAART, and protease inhibitor (PI) use. Ninety-eight participants (22%) had abnormal glucose tolerance (69 with IGT and 29 with diabetes). Among HIV-infected participants, 25% were on non-PI HAART and 52% were on PI HAART, but HAART and PI use were not associated with insulin resistance or abnormal glucose tolerance. Among obese participants, abnormal glucose tolerance was more common in HCV-seropositive than seronegative individuals, whereas among non-obese participants there was no association. CONCLUSION: The potential impact of HCV co-infection and obesity on glucose metabolism should be recognized in clinical care, and addressed in future research studies of HIV-infected individuals.

Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection.

BACKGROUND: Osteopenia has been described in HIV-infected persons, but most studies have not focused on aging men, have not included an HIV-negative comparison group with similar risks to those of the HIV-infected men, or lacked data on fracture rates. METHODS: We analyzed bone mineral density (BMD) and incident fractures in 559 men who were >or= 49 years old with or at-risk for HIV, including 328 with and 231 without HIV infection. RESULTS: Median age was 55 years, 56% were black and 89% had used illicit drugs. In unadjusted analysis, BMD was lower in HIV-infected compared with HIV-uninfected men at the femoral neck (0.97 +/- 0.14 versus 1.00 +/- 0.15 g/cm; P < 0.05) and lumbar spine (1.17 +/- 0.20 versus 1.20 +/- 0.21 g/cm; P = 0.06); both differences were significant (P < 0.05) after adjusting for age, weight, race, testosterone level, and prednisone and illicit drug use. Non-black race and body weight were independently associated with BMD at both measurement sites and methadone therapy was independently associated with spine BMD. Among HIV-infected men, 87% had taken antiretrovirals and 74% had taken protease inhibitors, but their use was not associated with BMD. Among men who had at least one subsequent study visit (94%), incident fracture rates per 100 person-years differed among men with normal BMD, osteopenia and osteoporosis (1.4 versus 3.6 versus 6.5; P < 0.01). A 38% increase in fracture rate among HIV-infected men was not statistically significant. CONCLUSIONS: HIV infection is independently associated with modestly reduced BMD in aging men, and decreased BMD is associated with increased fracture risk.

Incidence and persistence of Staphylococcus aureus nasal colonization in a community sample of HIV-infected and -uninfected drug users.

A longitudinal study of 282 community-based drug users was conducted from February 1999 through September 2000. Both the incidence (15.0 cases per 100 person-years at risk; 95% confidence interval, 10.2-20.7 cases per 100 person-years at risk) and persistence of Staphylococcus aureus carriage were increased among human immunodeficiency virus (HIV)-seropositive individuals.

Nutritional biomarkers associated with gynecological conditions among US women with or at risk of HIV infection.

BACKGROUND: Women infected with HIV face a combination of health threats that include compromised nutrition and adverse gynecological conditions. This relation among HIV, nutrition, and gynecological conditions is complex and has rarely been investigated. OBJECTIVE: Our objective was to investigate nutritional biomarkers associated with several gynecological conditions among US women with or at risk of HIV infection. DESIGN: Data on 369 HIV-infected and 184 HIV-uninfected women with both nutritional and gynecological outcomes were analyzed from a cross-sectional nutritional substudy of the HIV Epidemiology Research Study (HERS). We examined micronutrient distributions comparing HIV-infected with HIV-uninfected participants and both subgroups with the US population. We then modeled the relation of 16 micronutrient serum concentrations to various gynecological conditions, producing partially adjusted odds ratios, adjusted for study site, risk cohort, and HIV status. RESULTS: HIV-infected women's median antioxidant concentrations were lower than the medians of the US population. HERS women had lower median concentrations for vitamin A, selenium, and zinc irrespective of HIV status. Trichomoniasis prevalence was inversely related to serum alpha-carotene. Lower concentrations of vitamins A, C, and E and beta-carotene were associated with an increased risk of bacterial vaginosis. Higher concentrations of serum zinc were associated with lower risk of human papillomavirus. Candida colonization was higher among women with higher concentrations of total-iron-binding capacity. CONCLUSION: We identified several significant associations of micronutrient concentrations with the prevalence of gynecological conditions. These findings warrant further investigation into possible causal relations.

Current sexual activity and risky sexual behavior in older men with or at risk for HIV infection.

In a cross-sectional analysis, we investigated frequency of sexual activity and factors associated with risky sexual behavior among 624 oldermen, aged 49-80, with or at risk for HIV infection. During the prior 6 months, 75% reported sexual activity with at least one partner, and one quarter of both the HIV-negative and HIV-positive men had more than one sexual partner. Only 18% of the HIV-negative men and 58% of the HIV-positive men always used condoms with their sexual partners. Factors independently and positively associated with risky sexual behavior included lack of HIV infection, any drug use in the past 6 months, greater importance of sex in one's life, weekly or more frequent sexual activity in the past 6 months, and ever taking sildenafil. These results suggest that older men with or at risk for HIV infection are sexually active, participate in risky sexual behavior, and need safer sex interventions.

Hepatitis C infection is associated with lower lipids and high-sensitivity C-reactive protein in HIV-infected men.

Increased cardiovascular risk has been linked to HIV infection and combination antiretroviral therapy, but the impact of hepatitis C virus (HCV) status on indices of cardiovascular risk has not been routinely assessed in the HIV-infected population. The objective of this study was to analyze associations of HCV, HIV, and combination antiretroviral therapy with lipid levels and C-reactive protein (CRP) among older men. We measured fasting total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and high-sensitivity CRP serum levels in a cross-sectional study of 108 HIV-infected and 74 HIV-uninfected at-risk older men. One hundred ten men (60%) had detectable HCV RNA, with no difference by HIV status (p = 0.25). The majority (88%) of men with HCV infection had a history of injection drug use. Among all men, HCV infection was independently associated with lower total cholesterol (p < 0.001), LDL-C (p < 0.001), triglycerides (p = 0.01), and CRP (p = 0.001). Among HIV-infected men, HCV infection was associated with lower total cholesterol (p < 0.001), LDL-C (p < 0.001), and CRP (p = 0.004). HCV infection was associated with lower triglycerides among men on protease inhibitors (PI) (p = 0.02) and non-PI combination antiretroviral therapy (p = 0.02), but not among antiretroviral-naïve men. These findings demonstrate an association of lower serum lipid and CRP levels with HCV infection and suggest that HCV status should be assessed as an important correlate of cardiovascular risk factors in studies of older men with or at risk for HIV.

Two-step tuberculin skin testing in drug users.

To assess the utility of booster testing and to identify factors associated with a positive booster test, two-step tuberculin testing was performed in drug users recruited from methadone treatment. Participants also received a standardized interview on demographics and testing for HIV and CD4+ lymphocyte count. Of 619 enrollees completing the protocol, 174 (28%) had a positive PPD and 24 of the remaining 445 (5%) had a positive booster test. On multivariate analysis, boosting was associated with older age (adjusted odds ratio [ORadj] 2.38/decade, 95% confidence interval [CI] 1.34-4.22), history of using crack cocaine (ORadj 2.61, 95% CI 1.10-6.18) and a history of working as a home health aide (ORadj 4.23, 95% CI 1.39-12.86). Two-step tuberculin skin testing increased the proportion of participants with latent tuberculosis infection from 22% to 25%. Given the effectiveness of chemoprophylaxis, booster testing should be considered when drug users are screened for tuberculosis infection.

Gender differences in illicit substance use among middle-aged drug users with or at risk for HIV infection.

OBJECTIVE: The objective of the present study was to examine gender differences and other factors associated with current heroin and cocaine use among middle-aged drug users. METHODS: Baseline data were merged from 2 studies of men and of women with or at risk for HIV infection. Analysis was restricted to study participants who had ever used heroin or cocaine and who were 49-60 years of age at the time that they were interviewed. HIV-antibody status, drug-use history, and psychosocial and sociodemographic data were examined. Logistic regression models were used to assess factors independently associated with current heroin and cocaine use. RESULTS: Of 627 persons who ever used heroin and/or cocaine, 250 (39.9%) reported using these drugs within 6 months of the study interview conducted at baseline. Men were more likely to be using drugs currently, compared with women (42.3% vs. 28.2%; P = .007). In multivariate analysis, men, unemployed persons, and HIV-seronegative persons were more likely to be using heroin or cocaine at the time of the interview. In addition, current marijuana users, persons drinking alcohol on a daily basis, and persons who had been homeless in the 6 months before the interview were also more likely to be using these drugs. CONCLUSION: A relatively high proportion of middle-aged substance users with or at risk for HIV infection, especially men, may continue to use illicit drugs into the sixth decade of life. The differences noted between men and women who have used heroin and/or cocaine at some point in their lives suggest that special attention be given to aging and gender issues in framing HIV-prevention and drug-treatment programs.