DRD2 and DRD4 genes related to cognitive deficits in HIV‑infected adults who abuse alcohol

Background HIV-infected individuals continue to experience neurocognitive deterioration despite virologically successful treatments. The causes of neurocognitive impairment are still unclear. However, several factors have been suggested including the role of genetics. There is evidence suggesting that neurocognitive impairment is heritable and individual differences in cognition are strongly driven by genetic variations. The contribution of genetic variants affecting the metabolism and activity of dopamine may influence these individual differences. Methods The present study explored the relationship between two candidate genes (DRD4 and DRD2) and neurocognitive performance in HIV-infected adults. A total of 267 HIV-infected adults were genotyped for polymorphisms, DRD4 48 bp-variable number tandem repeat (VNTR), DRD2 rs6277 and ANKK1 rs1800497. The Short Category (SCT), Color Trail (CTT) and Rey-Osterrieth Complex Figure Tests (ROCT) were used to measure executive function and memory. Results Results showed significant associations with the SNP rs6277 and impaired executive function (odds ratio = 3.3, 95 % CI 1.2–2.6; p = 0.004) and cognitive flexibility (odds ratio = 1.6, 95 % CI 2.0–5.7; p = 0.001). The results were further stratified by race and sex and significant results were seen in males (odds ratio = 3.5, 95 % CI 1.5–5.5; p = 0.008) and in African Americans (odds ratio = 3.1, 95 % CI 2.3–3.5; p = 0.01). Also, DRD4 VNTR 7-allele was significantly associated with executive dysfunction. Conclusion The study shows that genetically determined differences in the SNP rs6277 DRD2 gene and DRD4 48 bp VNTR may be risk factors for deficits in executive function and cognitive flexibility

Serotonin-Related Gene Polymorphisms and Asymptomatic Neurocognitive Impairment in HIV-Infected Alcohol Abusers

HIV-infected individuals continue to experience neurocognitive deterioration despite virologically successful treatments. While the cause remains unclear, evidence suggests that HIV-associated neurocognitive disorders (HAND) may be associated with neurobehavioral dysfunction. Genetic variants have been explored to identify risk markers to determine neuropathogenesis of neurocognitive deterioration. Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life and HIV risk-taking behaviors. Single nucleotide polymorphisms in the SLC6A4, TPH2, and GALM genes may affect the activity of serotonin and increase the risk of HAND. The present study explored the relationship between SLC6A4, TPH2, and GALM genes and neurocognitive impairment in HIV-infected alcohol abusers. A total of 267 individuals were genotyped for polymorphisms in SLC6A4 5-HTTLPR, TPH2 rs4570625, and GALM rs6741892. To assess neurocognitive functions, the Short Category and the Auditory Verbal Learning Tests were used. TPH2 SNP rs4570625 showed a significant association with executive function in African American males (odds ratio 4.8, 95% CI, 1.5–14.8; ). Similarly, GALM SNP rs6741892 showed an increased risk with African American males (odds ratio 2.4, 95% CI, 1.2–4.9; ). This study suggests that TPH2 rs4570625 and GALM rs6741892 polymorphisms may be risk factors for HAND

Exploring substance use and HIV treatment factors associated with neurocognitive impairment among people living with HIV/AIDS

Neurocognitive (NC) impairment remains prevalent among people living with HIV (PLWH) and may be exacerbated by alcohol and drug use. This cross-sectional study assesses the degree to which alcohol and other drug use, time from HIV diagnosis to treatment, and years living with HIV affect three areas of NC functioning among HIV-seropositive adults. NC functioning in 370 PLWH living in Miami, FL was assessed using the Auditory Verbal Learning Test, the Short Category Test, Booklet Format, and the Color Trails Test 2 (CTT2). Participants reported the number of days using alcohol, marijuana, and cocaine over the previous 3 months, the number of known years living with HIV and length of time from HIV diagnosis to seeking care. Bivariate linear regression and multivariate linear regression were used to test associations between independent and dependent variables. Mean scores on NC measures were significantly lower than published norms; 39% of participants scored ≥1 standard deviation below normative sample means on \u3e2 NC tests. No significant associations were found between alcohol or cocaine use and any NC measure. Years living with HIV was associated with CTT2 in the bivariate analysis (β = 1.031; p = 0.007). In multivariate analysis, each day of marijuana use and years living with HIV were associated with a 0.32 (p = 0.05) point and 1.18 (p = 0.03) points poorer performance score on the CTT2, respectively. Results suggest that both marijuana use and duration of HIV infection may affect cognitive functioning among PLWH in ways that may impair their ability to follow important treatment guidance

The Effect of Mentholated Cigarette Use on interleukin-6 Responses Across Different HIV Positive Race/Ethnic Subgroups

In this report, we analyze trends in interleukin-6 (IL-6) production in people living with human immunodeficiency virus (PLWH), as a function of smoking behaviors and race, using a clinic-based case-control design. Peripheral blood mononuclear cells (PBMCs) were collected from a multiethnic cohort of 120 PLWH to measure IL-6 in culture supernatant. The data indicated that stimulated PBMC produced significantly higher levels of IL-6 in smokers than nonsmokers. However, as expected, this relationship was substantially modified by race. The distinctive production of IL-6 across different racial groups highlights the need for additional studies and suggests that African American smokers have enhanced production of IL-6 than other groups. Additional analyses indicate that higher IL-6 levels are related to the predicted use of mentholated cigarettes, which are more frequently used by African Americans. These findings warrant further investigation and indicate the critical need for tailored preventive interventions

Rapid Training and Implementation of the Pollock Technique, a Safe, Effective Newborn Circumcision Procedure, in a Low-Resource Setting

Male circumcision is highly protective against urinary tract infections, inflammatory conditions of the penis, sexually transmitted infections, and urogenital cancers. We aimed to reintroduce newborn male circumcision through the creation of a training program in Port-au-Prince, Haiti?an area with a considerable burden of preventable urogenital infections, sexually transmitted infections, and low circumcision rate?after an earlier study reported that a majority of Haitian medical providers were in need of and wanted newborn circumcision training. The program was conducted at the GHESKIO Health Centers, a large, non-governmental clinic offering comprehensive pediatric and adult health services. Two Haitian obstetricians and seven nurses learned circumcision procedures. On training completion, one of two obstetricians achieved surgical competence. Introduction of a newborn male circumcision training program was feasible, achieving an acceptable rate of procedural competency and high-quality services. Permanent resources now exist in Haiti to train additional providers to perform newborn male circumcisions

Knowledge, Attitudes, Practices and Beliefs about Medical Male Circumcision (MMC) among a Sample of Health Care Providers in Haiti

Background Haiti has the highest number of people living with HIV infection in the Caribbean/Latin America region. Medical male circumcision (MMC) has been recommended to help prevent the spread of HIV. We sought to assess knowledge, attitudes, practices and beliefs about MMC among a sample of health care providers in Haiti. Methods A convenience sample of 153 health care providers at the GHESKIO Centers in Haiti responded to an exploratory survey that collected information on several topics relevant to health providers about MMC. Descriptive statistics were calculated for the responses and multivariable logistic regression was conducted to determine opinions of health care providers about the best age to perform MMC on males. Bayesian network analysis and sensitivity analysis were done to identify the minimum level of change required to increase the acceptability of performing MMC at age less than 1 year. Results The sample consisted of medical doctors (31.0%), nurses (49.0%), and other health care professionals (20.0%). Approximately 76% showed willingness to offer MMC services if they received training. Seventy-six percent believed that their male patients would accept circumcision, and 59% believed infancy was the best age for MMC. More than 90% of participants said that MMC would reduce STIs. Physicians and nurses who were willing to offer MMC if provided with adequate training were 2.5 (1.15–5.71) times as likely to choose the best age to perform MMC as less than one year. Finally, if the joint probability of choosing “the best age to perform MMC” as one year or older and having the mistaken belief that MMC prevents HIV entirely is reduced by 63% then the probability of finding that performing MMC at less than one year acceptable to health care providers is increased by 35%. Conclusion Participants demonstrated high levels of knowledge and positive attitudes towards MMC. Although this study suggests that circumcision is acceptable among certain health providers in Haiti, studies with larger and more representative samples are needed to confirm this finding