Effect of ageing on neurocognitive function by stage of HIV infection: evidence from the Multicenter AIDS Cohort Study.

BACKGROUND: The demographics of the HIV epidemic in the USA have shifted towards older age. We aimed to establish the relationship between the processes of ageing and HIV infection in neurocognitive impairment. METHODS: With longitudinal data from the Multicenter AIDS Cohort Study, a long-term prospective cohort study of the natural and treated history of HIV infection among men who have sex with men in the USA, we examined the effect of ageing, HIV infection (by disease stage), and their interaction on five neurocognitive domains: information processing speed, executive function, episodic memory, working memory, and motor function. We controlled for duration of serostatus in a subanalysis, as well as comorbidities and other factors that affect cognition. Analyses were by linear mixed models for longitudinal data. FINDINGS: 5086 participants (47 886 visits) were included in the analytic sample (2278 HIV-seropositive participants contributed 20 477 visits and 2808 HIV-seronegative control participants contributed 27 409 visits). In an a-priori multivariate analysis with control variables including comorbidities and time since seroconversion, significant, direct negative effects of ageing were noted on all neurocognitive domains (p<0·0001 for all). Similar effects were noted for late-stage HIV disease progression on information processing speed (p=0·002), executive function (p<0·0001), motor function (p<0·0001), and working memory (p=0·001). Deleterious interaction effects were also noted in the domains of episodic memory (p=0·03) and motor function (p=0·02). INTERPRETATION: A greater than expected effect of ageing on episodic memory and motor function with advanced stages of HIV infection suggests that these two domains are most susceptible to the progression of neurocognitive impairment caused by ageing in individuals with HIV. This deficit pattern suggests differential damage to the hippocampus and basal ganglia (specifically nigrostriatal pathways). Older individuals with HIV infection should be targeted for regular screening for HIV-associate neurocognitive disorder, particularly with tests referable to the episodic memory and motor domains. FUNDING: National Institute of Mental Health.

Stimulant use and progression to AIDS or mortality after the initiation of highly active antiretroviral therapy.

BACKGROUND: HIV-positive persons who use stimulants (eg, methamphetamine) experience profound health disparities, but it remains unclear whether these persist after highly active antiretroviral therapy (HAART) initiation. Conducted within the Multicenter AIDS Cohort Study, this investigation examined whether stimulant use is associated with progression to AIDS or all-cause mortality after the initiation of HAART. METHODS: Using marginal structural modeling, the cumulative proportion of visits where any stimulant use was reported (ie, 0%, 1%-49%, 50%-99%, and 100%) was examined as a time-varying predictor of (1) all-cause mortality and (2) AIDS or all-cause mortality. RESULTS: Among the 1313 men who have sex with men (MSM) who initiated HAART, findings showed no significant association of any level of stimulant use with all-cause mortality. A competing risk analysis indicated that no level of stimulant use was associated with increased AIDS-related or non-AIDS mortality separately. Among the 648 participants without AIDS at HAART initiation, a secondary analysis indicated that stimulant use at 50% or more of study visits was associated with a 1.5-fold increase in the odds of progression to AIDS or all-cause mortality (adjusted odds ratio = 1.54; 95% confidence interval: 1.02 to 2.33; P < 0.05). CONCLUSIONS: HIV-positive stimulant-using MSM receiving HAART seem to face no greater overall risks for all-cause, AIDS-related, or non-AIDS mortality compared with nonusers. However, men without AIDS at HAART initiation who more frequently reported stimulant use demonstrated modestly increased odds of progression to AIDS or all-cause mortality. Comprehensive approaches are needed to optimize the effectiveness of HAART with stimulant-using MSM.

Sexual risk trajectories among MSM in the United States: implications for pre-exposure prophylaxis delivery.

BACKGROUND: Despite evidence supporting pre-exposure prophylaxis (PrEP) efficacy, there are concerns regarding the feasibility of widespread PrEP implementation among men who have sex with men (MSM). To inform the development of targeted PrEP delivery guidelines, sexual risk trajectories among HIV-negative MSM were characterized. METHODS: At semiannual visits from 2003 to 2011, HIV-negative MSM (N = 419) participating in the Multicenter AIDS Cohort Study provided data on sexual risk behaviors (SRBs) since their last visit. Based on their reported behaviors, participants were assigned a SRB score at each visit as follows: 0 = no insertive or receptive anal intercourse, 1 = no unprotected insertive or receptive anal intercourse, 2 = only unprotected insertive anal intercourse, 3 = unprotected receptive anal intercourse with 1 HIV-negative partner, 4 = condom serosorting, 5 = condom seropositioning, and 6 = no seroadaptive behaviors. Group-based trajectory modeling was used to examine SRB scores (<4 vs. ≥4) and identify groups with distinct sexual risk trajectories. RESULTS: Three sexual risk trajectory groups were identified: low-risk (n = 264; 63.0%), moderate-risk (n = 96; 22.9%; mean duration of consecutive high-risk intervals ∼1 year), and high-risk (n = 59; 14.1%; mean duration of consecutive high-risk intervals ∼2 years). Compared to low-risk group membership, high-risk group membership was associated with younger age (in years) [adjusted odds ratio (AOR) = 0.92, 95% confidence interval (CI): 0.88 to 0.96], being White (AOR = 3.67, 95% CI: 1.48 to 9.11), earning an income ≥$20,000 (AOR = 4.98, 95% CI: 2.13 to 11.64), distress/depression symptoms (Center for Epidemiologic Studies Depression Scale ≥ 16) (AOR = 2.36, 95% CI: 1.14 to 4.92), and substance use (AOR = 2.00, 95% CI: 1.01 to 3.97). CONCLUSIONS: Screening for the sociodemographic and behavioral factors described above may facilitate targeted PrEP delivery during high-risk periods among MSM.

Uptake and predictors of anal cancer screening in men who have sex with men.

OBJECTIVES: We investigated attitudes about and acceptance of anal Papanicolaou (Pap) screening among men who have sex with men (MSM). METHODS: Free anal Pap screening (cytology) was offered to 1742 MSM in the Multicenter AIDS Cohort Study, who reported history of, attitudes about, and experience with screening. We explored predictors of declining screening with multivariate logistic regression. RESULTS: A history of anal Pap screening was uncommon among non-HIV-infected MSM, but more common among HIV-infected MSM (10% vs 39%; P < .001). Most participants expressed moderate or strong interest in screening (86%), no anxiety about screening (66%), and a strong belief in the utility of screening (65%). Acceptance of screening during this study was high (85%) across all 4 US sites. Among those screened, most reported it was "not a big deal" or "not as bad as expected," and 3% reported that it was "scary." Declining to have screening was associated with Black race, anxiety about screening, and low interest, but not age or HIV status. CONCLUSIONS: This study demonstrated high acceptance of anal Pap screening among both HIV-infected and non-HIV-infected MSM across 4 US sites.

Joint effects of alcohol consumption and high-risk sexual behavior on HIV seroconversion among men who have sex with men.

OBJECTIVE: To estimate the effects of alcohol consumption and number of unprotected receptive anal intercourse partners on HIV seroconversion while appropriately accounting for time-varying confounding. DESIGN: Prospective cohort of 3725 HIV-seronegative men in the Multicenter AIDS Cohort Study between 1984 and 2008. METHODS: Marginal structural models were used to estimate the joint effects of alcohol consumption and number of unprotected receptive anal intercourse partners on HIV seroconversion. RESULTS: Baseline self-reported alcohol consumption was a median 8  drinks/week (quartiles: 2, 16), and 30% of participants reported multiple unprotected receptive anal intercourse partners in the prior 2 years. Five hundred and twenty-nine HIV seroconversions occurred over 35 ,870 person-years of follow-up. After accounting for several measured confounders using a joint marginal structural Cox proportional hazards model, the hazard ratio for seroconversion associated with moderate drinking (1-14 drinks/week) compared with abstention was 1.10 [95% confidence limits: 0.78, 1.54] and for heavy drinking (>14 drinks/week) was 1.61 (95% confidence limits: 1.12, 2.29) (P for trend <0.001). The hazard ratios for heavy drinking compared with abstention for participants with 0-1 or more than 1 unprotected receptive anal intercourse partner were 1.37 (95% confidence limits: 0.88, 2.16) and 1.96 (95% confidence limits: 1.03, 3.72), respectively (P for interaction = 0.42). CONCLUSION: These findings suggest that alcohol interventions to reduce heavy drinking among men who have sex with men should be integrated into existing HIV prevention activities.

The cumulative effects of medication use, drug use, and smoking on erectile dysfunction among men who have sex with men.

INTRODUCTION: Erectile dysfunction (ED) is highly prevalent among human immunodeficiency virus-seropositive (HIV+) men who have sex with men (MSM). There is a need for additional research to determine the correlates of HIV+ and HIV-seronegative (HIV-) MSM, especially regarding nonantiretroviral medication use. AIMS: This study examined the prevalence of ED and the sociodemographic, medical conditions, medication use, and substance use correlates of ED among HIV+ and HIV- MSM. METHODS: A modified version of the International Index of Erectile Function (IIEF) for MSM was self-administered by participants enrolled in the Multicenter AIDS Cohort Study, an ongoing prospective study of the natural and treated histories of HIV infection among MSM in the United States. The study sample included 1,340 participants, including 612 HIV+ and 728 HIV- men. Poisson regression with robust error variance was used to estimate prevalence ratios of ED in multivariable models in combined (HIV+/-) and separate analyses. MAIN OUTCOME MEASURE: ED was determined by the summed scores of a modified version of the IIEF validated among MSM. RESULTS: Twenty-one percent of HIV+ MSM and 16% of HIV- MSM reported ED. Being >55 years of age, black race, cumulative pack years of smoking, cumulative antihypertensive use, and cumulative antidepressant use had significant positive associations with the prevalence of ED in the total sample. Among HIV+ men, duration of antihypertensive use and antidepressant use were significantly associated with increasing prevalence of ED. Among HIV- men, being >55 years of age, black race, and cigarette smoking duration were associated with increased prevalence of ED. CONCLUSION: Predictors of ED may differ by HIV status. Although smoking cessation and effective medication management may be important as possible treatment strategies for ED among all MSM, there may be a burden on sexual functioning produced by non-HIV medications for HIV+ men.

A prospective study of alcohol consumption and HIV acquisition among injection drug users.

OBJECTIVE: to estimate the effect of alcohol consumption on HIV acquisition while appropriately accounting for confounding by time-varying risk factors. DESIGN: african-American injection drug users in the AIDS Link to Intravenous Experience cohort study. Participants were recruited and followed with semiannual visits in Baltimore, Maryland between 1988 and 2008. METHODS: marginal structural models were used to estimate the effect of alcohol consumption on HIV acquisition. RESULTS: at entry, 28% of 1525 participants were women with a median (quartiles) age of 37 (32-42) years and 10 (10-12) years of formal education. During follow-up, 155 participants acquired HIV and alcohol consumption was 24, 24, 26, 17, and 9% for 0, 1-5, 6-20, 21-50, and 51-140 drinks per week over the prior 2 years, respectively. In analyses accounting for sociodemographic factors, drug use, and sexual activity, hazard ratios for participants reporting 1-5, 6-20, 21-50, and 51-140 drinks per week in the prior 2 years compared to participants who reported 0 drinks per week were 1.09 (0.60-1.98), 1.18 (0.66-2.09), 1.66 (0.94-2.93), and 2.12 (1.15-3.90), respectively. A trend test indicated a dose-response relationship between alcohol consumption and HIV acquisition (P value for trend = 9.7 × 10). CONCLUSION: a dose-response relationship between alcohol consumption and subsequent HIV acquisition is indicated, independent of measured known risk factors.

Breaking the bond between stimulant use and risky sex: a qualitative study.

Stimulant-using men who have sex with men (MSM) are at increased risk for human immunodeficiency virus (HIV) transmission, and are more likely to practice unprotected anal sex than MSM who do not use methamphetamine and/or crack cocaine. In this paper the authors report on interviews with stimulant-using men who have sex with men who have participated in Crystal Meth Anonymous and other 12-step groups, focusing on those who did not have unprotected anal intercourse during a 6-month follow-up period and their reasons for doing so. The authors find 4 common themes cited: a diminished sexual drive; exclusive sex with a primary partner; greater sense of responsibility/commitment to safer sex; and most commonly of the four, an overall healthier sex life. Participants' use of terms such as "healthy," "enjoyable," and "fulfilling" to describe sex not on stimulants, and avoidance of these terms for sex on stimulants, suggests a distinct dimension of sexual experience.

Determinants of alcohol consumption in HIV-uninfected injection drug users.

We assess the association between time fixed and time varying participant characteristics and subsequent alcohol consumption in 1968 injection drug users (median age 37 years, 28% female, 90% African-American) followed semi-annually from 1988 to 2008. Median alcohol consumption was seven drinks per week at study entry (first and third quartile: 1, 26) with 36% reporting binge drinking. Alcohol consumption and binge drinking decreased over follow-up. Older individuals and women reported consuming fewer drinks per week. Higher typical alcohol consumption was reported by those participants who reported in the prior 6 months: non-injection cocaine use, injection drug use, having one or more sex partners, or among men, a same sex partner. Associations were generally similar for drinks per week and binge drinking. This study demonstrates that in a large urban cohort of persons with a history of injection drug use, risky drug use and sexual risk behavior are associated with subsequent alcohol consumption.

Specific sex drug combinations contribute to the majority of recent HIV seroconversions among MSM in the MACS.

BACKGROUND: New HIV infections are being observed among men who have sex with men (MSM). Understanding the fusion of risky sexual behaviors, stimulant and erectile dysfunction drug use with HIV seroconversion may provide direction for focused intervention. METHODS: During the follow-up period (1998-2008), we identified 57 HIV seroconverters among 1667 initially HIV-seronegative men. Time to seroconversion was modeled using Cox proportional hazards regression analysis for 7 combinations of sex drugs (inhaled nitrites or "poppers", stimulants, and erectile dysfunction drugs) used at the current or previous semiannual visit, adjusting for other risk factors including sexual behavior, alcohol and other drugs used, and depression. Model-based adjusted attributable risks were then calculated. RESULTS: The risk of seroconversion increased linearly with the number of unprotected receptive anal sex partners (URASP), with hazard ratios ranging from 1.73 [95% confidence interval (CI): 0.75 to 4.01] for 1 partner, to 4.23 (95% CI: 1.76 to 10.17) for 2-4 partners, and to 14.21 (95% CI: 6.27 to 32.20) for 5+ partners, independent of other risk factors. After adjustment, risks for seroconversion increased from 2.99 (95% CI: 1.02 to 8.76) for men who reported using stimulants only (1 drug) to 8.45 (95% CI: 2.67 to 26.71) for men who reported using all 3 sex drugs. The use of any of the 7 possible sex drug combinations accounted for 63% of the 9-year HIV seroincidence in the Multicenter AIDS Cohort Study. When contributions of increased URASP and combination drug use were analyzed together, the total attributable risk for HIV seroconversion was 74%, with 41% attributable to URASP alone and a residual of 33% due to other direct or indirect effects of sex drug use. CONCLUSIONS: Use of poppers, stimulants, and erectile dysfunction drugs increased risk for HIV seroconversion significantly in this cohort. These data reinforce the importance of implementing interventions that target drug reduction as part of comprehensive and efficacious HIV prevention strategies.

Prospective study of attitudinal and relationship predictors of sexual risk in the multicenter AIDS cohort study.

We examined the influence of attitudes concerning HIV transmission, safe sex, and sexual sensation seeking, as well as negotiated risk reduction with primary partners, on the proportion of unprotected sexual partners (%UASP) among men who have sex with men (MSM). Participants were 263 HIV-seropositive and 238 HIV-seronegative MSM in the Multicenter AIDS Cohort Study between 1999 and 2003 who completed a 20-item attitude survey twice. Behavioral data were collected concurrently and 6-12 months after each survey. Among seropositives, decreased HIV concern and increased safer sex fatigue were associated with higher %UASP at 6 and 12 months. Among seronegatives, increased %UASP at 12 months was associated with safer sex fatigue. At 6 months and 12 months, risk reduction agreements were associated with increased %UASP among seronegatives in seroconcordant monogamous relationships, reflecting their abandonment of condoms in such partnerships. We conclude that HIV prevention efforts should target modifiable attitudes (reduced concern about HIV and safer sex fatigue) and increases in sexual risk-taking of MSM, particularly among HIV+ men having sex with serodiscordant partners.

Patterns and predictors of changes in adherence to highly active antiretroviral therapy: longitudinal study of men and women.

BACKGROUND: Adherence to therapy is a dynamic behavior. However, few studies have identified factors associated with changes in adherence to highly active antiretroviral therapy (HAART) among men and women. METHODS: From 1999 through 2004, self-reported adherence to HAART was recorded twice yearly as part of 2 prospective cohort studies. At each study visit, participants were categorized as being 100% adherent if they reported full adherence with their HAART regimen over the past 4 days (for men) and 3 days (for women). Repeated-measures logistic regression models were used to identify predictors for changes in adherence between consecutive visits. RESULTS: Of the participants, 640 men and 1304 women contributed 2803 and 5972 visit-pairs, respectively. Among white men, the prevalence of 100% adherence decreased from 91% in 1998 to 80% in 2003. Among women and African American men, the prevalence of full adherence was lower (75% and 77% on average, respectively) and stable over time (P>.6). In both cohorts, the presence of clinical symptoms was independently associated with decreasing adherence (odds ratio [OR], 1.38 in men and 1.48 in women). Depression in men (OR, 1.44) and use of alcohol in women (OR, 1.81, 1.52, and 1.29, for binge drinking, moderate-to-heavy drinking, and low consumption, respectively) also predicted decreasing adherence. In addition, the use of drugs by men and women (OR, 0.61 and 0.58, respectively) and alcohol binging by women (OR, 0.41) were negatively associated with improving adherence. CONCLUSIONS: Adherence to antiretroviral treatment is a dynamic process; modifiable risk factors are associated with increasing and decreasing adherence, suggesting specific interventions. Moreover, the association of these risk factors with changes in adherence may differ by sex.

The relationship between methamphetamine and popper use and risk of HIV seroconversion in the multicenter AIDS cohort study.

BACKGROUND: The association between methamphetamine use and HIV seroconversion for men who have sex with men (MSM) was examined using longitudinal data from the Multicenter AIDS Cohort Study. METHODS: Seronegative (n = 4003) men enrolled in 1984 to 1985, 1987 to 1991, and 2001 to 2003 were identified. Recent methamphetamine and popper use was determined at the current or previous visit. Time to HIV seroconversion was the outcome of interest. Covariates included race/ethnicity, cohort, study site, educational level, number of sexual partners, number of unprotected insertive anal sexual partners, number of unprotected receptive anal sexual partners, insertive rimming, cocaine use at the current or last visit, ecstasy use at the current or last visit, any needle use since the last visit, Center for Epidemiologic Study of Depression symptom checklist score >16 since the last visit, and alcohol consumption. RESULTS: After adjusting for covariates, there was a 1.46 (95% confidence interval [CI]: 1.12 to 1.92) increased relative hazard of HIV seroconversion associated with methamphetamine use. The relative hazard associated with popper use was 2.10 (95% CI: 1.63 to 2.70). The relative hazard of HIV seroconversion increased with the number of unprotected receptive anal sexual partners, ranging from 1.87 (95% CI: 1.40 to 2.51) for 1 partner to 9.32 (95% CI: 6.21 to 13.98) for 5+ partners. The joint relative hazard for methamphetamine and popper use was 3.05 (95% CI: 2.12 to 4.37). There was a significant joint relative hazard for methamphetamine use and number of unprotected receptive anal sexual partners of 2.71 (95% CI: 1.81 to 4.04) for men with 1 unprotected receptive anal sexual partner, which increased in a dose-dependent manner for >1 partners. CONCLUSIONS: Further examination of the mechanisms underlying the synergism of drug use and sexual risk behaviors on rates of HIV seroconversion is necessary for the development of new targeted HIV prevention strategies for non-monogamous drug-using MSM.

The Bolger conference on PDE-5 inhibition and HIV risk: implications for health policy and prevention.

INTRODUCTION: Recent reports have linked the use of phosphodiesterase type 5 (PDE-5) inhibitors with increased rates of high-risk sexual behavior and HIV transmission in some individuals. AIM: A National Institute of Mental Health (NIMH)-funded, multidisciplinary conference was convened to evaluate scientific research, clinical and ethical considerations, and public policy implications of this topic. MAIN OUTCOME MEASURES: Published and unpublished findings on effects of PDE-5 inhibitors on sexual behavior; published guidelines and management recommendations. METHODS: Leading investigators in relevant disciplines (e.g., public health, epidemiology, medical ethics, urology, psychology) participated in a 2-day meeting, including representatives of government, scientific, and regulatory agencies (the Centers for Disease Control, Food and Drug Administration, NIMH, and the National Institute on Drug Abuse). Panelists provided critical reviews of substantive areas of research, followed by question and answer sessions on each topic. On the second day, working groups were convened to identify critical gaps and priorities in three major areas: (i) research and evaluation needs; (ii) prevention strategies and clinical management issues; and (iii) policy and prevention implications. RESULTS: Research needs and priorities were categorized into four specific areas: (i) basic and clinical/laboratory research; (ii) epidemiology and risk factors; (iii) social-behavioral processes and interventions; and (iv) prevention/policy and educational needs. Identified gaps in the available data include populations at risk (e.g., risk among heterosexuals, risk profiles among subpopulations of men who have sex with men) and the specific role of PDE-5 inhibitors in HIV seroconversion. Specific areas of emphasis were the need for safer sex counseling, comprehensive sexually transmitted infection (STI) screening and follow-up when indicated, avoidance of potentially dangerous drug interactions, and potential benefits of testosterone replacement for HIV-positive men with decreased androgen and other symptoms of hypogonadism. Conclusions. A conference was convened on the topic of PDE-5 inhibition and HIV risk. This "white paper" summarizes the findings of the conference and recommendations for future research.

Viral load and HIV treatment attitudes as correlates of sexual risk behavior among HIV-positive gay men.

OBJECTIVES: People living with HIV who achieve an "undetectable" viral load may assume that they are less infectious, leading to increased sexual risk. We examined the relation between perceiving that one has an undetectable viral load and sexual risk taking among gay men. METHODS: HIV-positive participants (N=60) completed measures assessing HIV serostatus, perceived HIV viral load (detectable vs. undetectable), sexual risk and treatment attitudes. RESULTS: Contrary to hypotheses, HIV-positive men with detectable viral loads were more likely to report unprotected anal sex with a nonprimary partner than were men reporting undetectable viral loads. Although a significant minority endorsed the belief that an HIV-positive partner with an undetectable viral load is less infectious, this belief was unrelated to sexual risk. Multivariate analyses showed that the strongest predictor of sexual risk was a measure assessing participants' reduced concern over HIV stemming from the availability of improved HIV treatments. After controlling for reduced HIV concern, viral load status was no longer a significant predictor of risk. CONCLUSIONS: Results suggest that reduced concern about the consequences of HIV infection may be more important than perceived health status as a determinant of risky sex and highlight the need for continued prevention efforts among people who are HIV-positive.