The hypothesis that alcohol and HIV would exert an interactive effect on NP performance was upheld in the current investigation. Specifically, the findings supported the original hypotheses of a significant interaction between HIV status and alcohol consumption. Decrements in neurocognitive performance were found in HIV+ heavy drinkers and were more pronounced in domains preferentially affected by both HIV and alcohol use, specifically, psychomotor/motor speed and reaction time. Compared to other seropositives and to seronegative heavy drinkers, HIV seropositive heavy drinkers showed the slowest performance on these measures. Consistent with previous studies, the current investigation also demonstrated that HIV seropositive participants performed more poorly than seronegatives on measures of reaction time. However, no main effects for alcohol were obtained.
On two measures of psychomotor speed — Color Trails 1 and Color Trails 2 — seropositive heavy drinkers also performed more poorly than light drinkers, and among SNs moderate drinkers were slower than nondrinkers. On a measure of motor speed (Grooved Pegboard), SN moderate drinkers were slower than light drinkers. These findings are notable as no main effects were obtained for these domains. In general, in this sample serostatus differences were noted only among the heavy drinkers — suggesting the exacerbation of cognitive deficits when persons are co-morbid for HIV and alcohol use. The interaction between HIV status and alcohol use on measures of reaction time further suggests an exacerbation of the HIV-associated deficits in information processing in HIV+ heavy drinkers, who evidenced slower reaction times than nearly all seropositive groups. Examination of the figural depictions of the findings consistently reveal SP heavy drinkers to be performing more poorly than all other groups. The results of this study are consistent with previous reports of alcohol-related (Oscar-Berman et al., 1997
; Parsons & Nixon, 1993
; Rourke & Loberg, 1996
; Wilkinson & Poulos, 1987
) and HIV-associated (Evans & Mason, 2002
; Grant et al., 1987
; Heaton et al., 1995
; Hinkin, van Gorp, & Satz, 1995
) neurocognitive deficits. In addition, the current investigation provides evidence that HIV infection and heavy alcohol use interact to exacerbate neurocognitive dysfunction.
No main effects or interactions were noted for any of the memory measures. As reported previously, studies have shown that persons diagnosed with alcohol abuse/dependence and those with long periods of alcohol use show impairment on measures of learning and memory (Bondi et al., 1998
; Wilkinson & Poulos, 1987
). Our failure to find an alcohol effect on measures of memory may be due to the amount of alcohol consumed in those individuals classified as “moderate” and “heavy” drinkers. Those classified as “heavy” drinkers in this study may not have met criteria as alcohol dependent in contrast to those in studies that found evidence of memory impairment. In addition, the lack of significant findings on tests of nonverbal memory may also be in part because this measure (Picture Memory Interference Test) has not been validated or empirically tested with HIV+ individuals, and as such, its utility in detecting HIV related memory deficits is unknown.
Examination of the pattern of results reveals that HIV+ moderate drinkers tended to perform better than HIV+ nondrinkers and light drinkers while among the seronegatives, moderate drinkers performed more poorly than all other alcohol groups (however, these findings did not reach statistical significance). It is possible than alcohol groups differed in their pattern of use between serostatus groups, and that seronegative moderate drinkers in our study were more likely to have more episodes of binge drinking, which may be more damaging to the CNS. Thus, heavy drinkers may drink more overall, but demonstrate a more stable
drinking pattern with fewer episodes of binge drinking. It is also possible that although we controlled for frequency and pattern of drug use (% using drugs more than once per week), the actual amount
of drugs used by the SN moderate drinkers was more than that used by heavy drinkers. Moderate drinkers might also be more prone to use alcohol to “come down” after a drug binge than heavy drinkers. Therefore, the poorer performance of moderate drinkers relative to other groups might be due to differences in both pattern and amount of alcohol and drug use between these groups. The slightly better performance by moderate drinking seropositives may be an artifact of our alcohol measurement and lack of historical data. The seropositive moderate drinkers may represent a healthier subset of the sample and as such have not engaged in major changes in behaviors such as alcohol consumption in response to health concerns. Green et al. (2004)
noted that, contrary to expectations, persons with histories of alcohol abuse reported less current consumption than those without such histories, and they attributed this to the possibility that people with abuse histories may have made lifestyle changes. It is possible that in our study this was true as well and the nondrinkers/light drinkers represent persons who are abstinent or more controlled in drinking patterns following treatment. These hypotheses cannot be specifically tested with the current data and should be considered in future studies. However, subsequent analyses revealed that there were no demographic differences between moderate and heavy drinkers and there were no differences between the groups with respect to progression of HIV (as determined by the proportion of individuals in each group that met diagnostic criterion for AIDS).
A recent study by Green et al. (2004)
which examined the independent and interactive effects of alcohol abuse/dependence, HIV and neuropsychological performance in a small sample of HIV+ men obtained findings that are in part consistent with those obtained in this study. They found an interactive effect of alcohol abuse and HIV on executive functioning, verbal IQ and reaction time, and concluded that alcohol abuse and HIV can work synergistically to augment NP impairment. Their data is many ways deviates from ours (much smaller sample, not focused on minority men, more stringent exclusion criteria on the basis of head injury, the use of diagnostic alcohol abuse criteria), and yet the pattern of findings was generally similar. This highlights the likelihood that history of past, recent, and current alcohol consumption and abuse represent risk factors for cognitive impairment in HIV infected adults.
Our results are somewhat consistent with metabolic and electrophysiological findings of an additive effect of alcohol abuse and HIV infection (Fein et al., 1995
; Fein et al., 1998
; Meyerhoff et al., 1995
) and suggest a common neuropathological substrate for alcohol use and HIV infection, most likely frontal brain regions. Studies have found that alcoholics show significant reductions in cerebral blood flow in frontal regions and that these reductions are associated with poorer neuropsychological functioning (Oscar-Berman & Hutner, 1993
). Electrophysiological studies have also shown differences between alcoholic and non-alcoholic individuals over frontal areas (Zhang, Begleiter, & Porjesz, 1997
). It is also well-documented that HIV has an affinity for the frontal-subcortical neuronal pathway (Brew et al., 1988
; Navia et al., 1986
Immune suppression represents another possible mechanism for the additive effects of HIV infection. Bagasra et al. (1990)
argued that alcohol abuse may lead to increased systemic immune dysfunction in HIV seropositive individuals, which is consistent with findings of similar immunological deficits in alcoholics and those infected with HIV (Gentry, 1998
). A recent study found that even when controlling for adherence to HAART, HIV+ individuals with a history of alcohol use problems have lower CD4 and higher HIV RNA levels than non-drinkers (Traphagen, Freedberg, Horton, Tripp, & Samet, 2001
). This may be due to faster disease progression in alcohol users and abusers, poorer therapeutic efficacy of HAART in alcohol users and abusers, or some combination of these two mechanisms. However, a relationship between alcohol use and faster disease progression is not supported in these data, as cross sectional comparison of CD4 levels across the alcohol groups reveal no differences. It is also possible that heavy alcohol use decreases an individual's cognitive reserve, resulting in more deleterious neurocognitive deficits in HIV-infected alcohol users and abusers. Satz et al. (1993)
and Stern, Silva, Chaisson, & Evans, (1996)
have noted that HIV seropositive participants with low cognitive reserve perform worse on neuropsychological measures than HIV seronegative participants and HIV seropositive participants with high cognitive reserve, suggesting that low cognitive reserve puts individuals at risk for cognitive dysfunction.
The present findings may serve as a heuristic for ongoing assessment of this issue. The AAHP was a community sample of African American men, and as such provided an externally valid representation of the HIV epidemic in Los Angeles. However, the sample was recruited as part of a study of cocaine use, and as such, many participants had a long standing history of drug use and abuse. Ninety percent of this sample reported using drugs at least once during the past year, and the comorbidity of drug and alcohol use in this sample calls for caution in interpreting findings from this study. While drug use and recent drug exposure were covaried when appropriate, it is still possible that some of the effects being observed are due in part to drug use. In this sample, moderate and heavy drinkers were more likely than other groups to report current drug use and to have used cocaine within the past 72 hours. Past work using a subset of participants from this sample has revealed little effect of cocaine use on NP functioning, and no interactive effect of cocaine use and HIV on NP functioning (Durvasula et al., 2000
). Exploratory analyses revealed no relationship between self-report of marijuana use or recent exposure to marijuana as indexed by urine toxicology and NP performance. Less than 4% of the sample reported use of any substances other than cocaine or marijuana during the past year. Given past findings indicating little effect of drug use on NP functioning in this sample, these results are suggestive of an independent additive relationship between HIV and alcohol. Methodologically, it would be problematic to select a sample of HIV+ individuals who have histories of alcohol use without any drug abuse, and the uniqueness of such a sample may limit generalizability. However, our inability to definitively tease out the role of alcohol independent of drugs requires circumspection in interpretation of these findings. It is very possible that the alcohol-NP relationship observed in this sample may represent a cumulative effect of long-term drug AND alcohol use of which alcohol use may serve as a marker.
In addition, this study did not exclude participants who had a history of head injury or associated loss of consciousness. Again, to do so, would be to limit the generalizability of the sample. History of head injury secondary to impairments or accidents engendered by substance or alcohol use is not uncommon, and to exclude all persons with head injury/LOC history could result in a sample with limited ecological validity. In this sample, history of head injury or LOC was not associated with neuropsychological performance. The heavy alcohol use group did have a greater frequency of head injury and LOC history, and we recognize that a history of head injury may potentiate the effects of alcohol use and HIV, and we attempted to address this statistically by including head injury and LOC as a covariate.
The UCLA-WHO Neuropsychological test battery was employed in this study as it was believed to be more “culture-fair” and was comprised of traditional and newly developed tests that minimize the use of letters and numbers in favor of more universal stimuli such as shapes, colors, and pictorial and verbal representations of universal objects (e.g., body parts). While this battery has been shown to be useful in cross cultural settings to differentiate between HIV positive and negative participants in study sites as diverse as Germany and Zaire (Maj et al., 1993
), several of the measures have not been widely used in HIV research (e.g., Color Figure Mazes, Picture Memory Interference Test), and their utility in capturing HIV related cognitive deficits is not well established. In addition, while this sample was comprised of a sample of minority men, they were all literate, and the average level of education in this sample was 13 years. This may in part explain the presence of significant findings on the Color Trails Test without finding similar results for the Trail Making Test. While the Trail Making Test requires sequencing digits and dividing between letters and numbers — both likely to be overlearned stimuli for this sample — the Color Trails Test requires attending to both numerical sequence and color (which may be a relatively underused stimulus set for this group of participants). This is analogous to the loss of performance time typically observed on the color naming trial of the Stroop Color Word Interference Test relative to the word reading trial in literate children, adolescents, and adults. It is possible that Color Trails — although suggested to be a more “culture fair test” — may have actually challenged our participants more than the traditional Trail Making Test given the underlearned nature of the stimuli.
The present study also relied on amount of consumption to index alcohol use, and our measurement was limited to one year. As such, our conclusions reflect the impact of recent alcohol use, and do not permit generalizations about lifetime or longer term patterns of use. Bornstein et al. (1993)
actually found no associations between NP impairment and alcohol abuse/dependence in asymptomatic seropositives, though they did find that quantitative estimates of alcohol use in the past year were associated with executive functioning, attention, and motor speed. Many other studies of alcohol use and neuropsychological performance have examined samples of participants with diagnoses of alcohol abuse/dependence. As this study was not originally developed as a study of alcohol abuse/dependence, this was not assessed. In addition, we did not capture drinking patterns such as binge drinking. It is possible that moderate and heavy drinkers who were binge drinkers may have had different NP outcomes than those who drank the same number of drinks per week but fewer in any one sitting.
Overall, this suggests the need for multimodal measurements of alcohol use (diagnostic criteria, amount, toxicology/recent exposure, lifetime drinking patterns) to more precisely address this issue. While it is likely that a subset of the heavy and moderate drinkers in this study would have met diagnostic criteria for alcohol abuse or dependence, the majority likely did not. It is likely that if a sample of HIV+ individuals with a history of current or past alcohol abuse/dependence were assessed, these findings may be even more pronounced.
These data were gathered in the early-mid-1990s, prior to the advent of HAART. As such, these findings may not be as applicable to current cohorts of HIV infected persons. In addition, these findings may represent a more liberal test of our hypothesis, as HAART has been found to mitigate HIV related NP decline (Deutsch et al., 2001
). However, not all HIV positive individuals are receiving HAART, and many who do are nonadherent, which may result in therapeutic failure, and a diminished likelihood of CNS protection. Thus, while these data do not account for the impact of HAART on the relationship between HIV, alcohol and NP function, they do allow for description of the possible potentiation of NP decline in HIV as a function of alcohol use. Further work examining this question in current HIV infected cohorts receiving HAART is needed to empirically assess the impact of HAART in HIV+ alcohol abusers.
To our knowledge, this is the first study to examine the additive versus interactive effects of HIV and alcohol use on neurocognitive functioning in a community resident sample of African American men. The findings of the present investigation are important given the prevalence of alcohol use and abuse among individuals with HIV/AIDS and the current need to identify the problems associated with alcohol use in those with HIV/AIDS. Future studies should focus on the association between neuropsychological test performance and electrophysiological/metabolic measures of CNS functioning in seropositive alcohol users and abusers, with a close examination of activity and perfusion patterns in frontal and subcortical regions. In addition, the examination of differences in the progression
of HIV disease in alcoholics versus non-alcoholics would provide valuable information, particularly as it relates to the treatment of alcohol users/abusers infected with HIV. It would also be important to examine the effect that periods of abstinence have on neurocognitive functioning. Studies have consistently found that length of abstinence corresponds with neuropsychological performance and that there is recovery of function with periods of abstinence (Brandt, Butters, Ryan, & Bayog 1983
; Grant et al., 1987
). Future longitudinal studies could compare improvements in neurocognitive functioning in seropositive versus seronegative alcohol abusers after periods of abstinence. This study found computerized measures to be most sensitive to serostatus effects, alcohol effects, and the additive effects of the two. This highlights the importance of continuing to employ more sensitive computerized measures to capture the subtle deficits that result from HIV infection and alcohol use. Follow up studies should examine the practical implications of neurocognitive dysfunction in HIV+ alcohol users/abusers. Some investigations have suggested that alcohol and drug use are associated with nonadherence to HAART (Hinkin et al., 2002
; Lin, Sethi, Wu, Strathdee, Celentano, & Vlahov, 2002
; Sullivan & Nakamura, 2002
), while others have noted that neurocognition is related to nonadherence to HIV medication (Durvasula, Golin, & Miller, 1999
; Hinkin et al., 2001). Thus, it is possible that alcohol and HIV may also interact to negatively impact other important health behaviors such as HAART adherence.
In summary, the findings of the present study examining a large community sample of African American men are consistent with previous studies. The most notable finding, however, was the demonstration of an interactive effect of HIV status and alcohol consumption on neurocognitive functioning such that HIV+ individuals with patterns of heavy alcohol use demonstrated the worst performance relative to other seropositives as well as compared to seronegative heavy drinkers, particularly on measures of reaction time and psychomotor speed.
This study also highlights the importance of addressing the heterogeneity of HIV+ populations in NP studies. While serostatus effects were not consistently obtained, when the subset of heavy drinkers was examined, significant decrements were noted. Identification of characteristics that may compromise NP functioning such as alcohol use, drug use, history of head injury, premorbid IQ, and even low SES must be addressed to more precisely elucidate the NP sequelae of HIV infection. Neuropsychological investigations with HIV infected populations remain a methodologically challenging endeavor and results require cautious interpretation. HIV infected individuals in general appear to carry more “risky” histories (e.g., characterized by greater likelihood of drug use, neurological trauma, economic difficulties), and it is never possible to adequately “control” for all of these co-factors. As such, these results are not meant to suggest a singular explanatory role for alcohol but raise the likelihood that alcohol use, particularly heavy use, may serve as a potential marker, if not causative agent, for potentially more severe neuropsychological compromise in HIV infected individuals. Despite these limitations, the findings of this study suggest that HIV+ individuals with heavy alcohol use are at risk for neurocognitive dysfunction.