Helping our patients take HIV pre-exposure prophylaxis (PrEP): a systematic review of adherence interventions.

OBJECTIVES: Adherence is critical for maximizing the effectiveness of pre-exposure prophylaxis (PrEP) in preventing HIV infection. Strategies for promoting adherence to HIV treatment, and their potential application to PrEP adherence, have received considerable attention. However, adherence promotion strategies for prevention medications have not been well characterized and may be more applicable to PrEP. We aimed to identify adherence support interventions that have been effective in other prevention fields and could be applied in the HIV prevention context to support pill taking among PrEP users. METHODS: To identify adherence support interventions that could be evaluated and applied in the PrEP context, we conducted a systematic review across the following prevention fields: hypertension, latent tuberculosis infection, hyperlipidaemia, oral contraceptives, osteoporosis, malaria prophylaxis, and post-exposure prophylaxis for HIV infection. We included randomized controlled trials that evaluated the efficacy of interventions to improve adherence to daily oral medications prescribed for primary prevention in healthy individuals or for secondary prevention in asymptomatic individuals. RESULTS: Our searches identified 585 studies, of which 48 studies met the eligibility criteria and were included in the review; nine evaluated multiple strategies, yielding 64 separately tested interventions. Interventions with the strongest evidence for improving adherence included complex, resource-intensive interventions, which combined multiple adherence support approaches, and low-cost, low-intensity interventions that provided education or telephone calls for adherence support. CONCLUSIONS: Our review identified adherence interventions with strong evidence of efficacy across prevention fields and provides recommendations for evaluating these interventions in upcoming PrEP studies.

A study of perceived racial discrimination in Black men who have sex with men (MSM) and its association with healthcare utilization and HIV testing.

In HPTN 061, a study of Black men who have sex with men (MSM), we evaluated the association of healthcare-specific racial discrimination with healthcare utilization and HIV testing among 1167 HIV-negative participants. Median age was 38 years, 41 % were uninsured, and 38 % had an annual household income <$10,000. Overall, 19 % reported healthcare-specific racial discrimination directed toward family, friend, or self; 61 % saw a healthcare provider in the previous 6 months and 81 % HIV tested within the past year. Healthcare-specific racial discrimination was positively associated with seeing a provider [adjusted odds ratio (AOR) = 1.4 (1.0, 2.0)] and HIV testing [AOR = 1.6 (1.1, 2.4)] suggesting that barriers other than racial discrimination may be driving health disparities related to access to medical care and HIV testing among Black MSM. These results contrast with previous studies, possibly due to measurement or cohort differences, strategies to overcome discrimination, or because of greater exposure to healthcare.

A novel missense mutation T101N in the melanocortin-4 receptor gene associated with obesity.

Mutations in the melanocortin-4 receptor (MC4R) are associated with severe obesity, independent of their effect on cortisol or thyroid-stimulating hormone levels. We examined a morbidly obese male (BMI = 62 kg/m²) with a binge-eating disorder and eight family members for mutations in the MC4R gene and potential differences in leptin levels. Fifty healthy individuals served as controls. Sequence analysis revealed a novel heterozygous missense mutation (c.302 C>A, p.T101N) located in the second transmembrane domain of the receptor, which was not detected in controls. The Fisher exact test revealed an association between the T101N mutation and history of obesity (P < 0.05) in the family. The Kruskal-Wallis test showed an association between the mutation and the leptin/BMI ratio (P < 0.05), while there was no association between the T101N mutation and diabetes or arterial hypertension in the family. Although the available family was small, we could show a significant association between the heterozygous T101N mutation and obesity.

Maturity-Onset Diabetes of the Young (MODY) caused by a novel nonsense mutation E41X in the HNF-1α gene.

The most common cause of Maturity-Onset Diabetes of the Young (MODY) are mutations in the Hepatic Nuclear Factor 1α (HNF-1α) gene, resulting in MODY3. In a family afflicted with diabetes, a novel nonsense mutation in HNF-1α, E41X, causing a termination codon behind the dimerization domain, was found. The penetrance in individuals older than 25 years was 81.8%. The age at manifestation of diabetes ranged from 18 to 63 years, only 2 out of 10 diabetic individuals developed the disease at ages younger than 25 years. Although diabetes duration lasted up to 35 years in this family, only one family member suffered from diabetic complications. Additional polymorphisms in HNF-1α, I27L and S487N, were found in this pedigree. Despite its biological inactivity, S487N polymorphism led in combination with E41X to a significant earlier manifestation of diabetes, whereas I27L polymorphism or increased Body Mass Index (BMI) did not. In spite of the severe gene defect, which truncates the protein behind the dimerization domain, the phenotype of E41X was relatively benign without frequent diabetic complications.

Potentially exposed but uninfected individuals produce cytotoxic and polyfunctional human immunodeficiency virus type 1-specific CD8(+) T-cell responses which can be defined to the epitope level.

We measured CD8(+) T-cell responses in 12 potentially exposed but uninfected men who have sex with men by using cytokine flow cytometry. Four of the individuals screened exhibited polyfunctional immune responses to human immunodeficiency virus type 1 Gag or Vif. The minimum cytotoxic T lymphocyte epitope was mapped in one Gag responder.

Aryl hydrocarbon receptor interacting protein gene (AIP) mutations are rare in patients with hormone secreting or non-secreting pituitary adenomas.

OBJECTIVE: Recent data suggest that mutations in the aryl hydrocarbon receptor interacting protein gene (AIP) are associated with pituitary adenomas. AIP is considered to be a tumour suppressor gene. METHODS: 110 Caucasian patients living in Germany with pituitary adenoma (55 hormone secreting, 55 non-functioning) were examined for AIP mutations. RESULTS: Three patients (2.7%) harboured an AIP germline mutation. A heterozygous mutation, R16H (c.47G>A), was found in two patients and a heterozygous G>C change in the 3'UTR, 60 bp downstream of the termination codon, in one patient. All three patients suffered from non-functioning adenoma. Additionally, a silent polymorphism, D172D (c.516C>T), was found in 3 patients with non-functioning adenoma, in 2 patients with prolactinoma and in one patient with acromegaly. CONCLUSIONS: AIP mutations are rare in sporadic pituitary adenomas in the German population and occur independently from a hormone secretion of the adenoma.

The DG10S478 variant in the TCF7L2 gene is not associated with microvascular complications in type 2 diabetes.

OBJECTIVE: The DG10S478 variant in the transcription factor 7-like 2 (TCF7L2) gene is a tetranucleotide repeat with six alleles. Alleles 0, 8 and 12 were found to account for 98% of chromosomes in population based controls. The composite allele X (non zero) has been associated with type 2 diabetes while allele 0 (no insertion) was described as protective. However, no data exist about the influence of DG10S478 variants on manifestation of diabetes and development of diabetic complications. METHODS: 250 patients with type 2 diabetes were tested for the DG10S478 allele X and its association with diabetic complications, age at diagnosis of diabetes and BMI. RESULTS: Allele 0 was found in 42.4% of the examined patients, 45.2% of the participants were found to be heterozygous and 12.4% homozygous for the composite allele X. The correlation of allele X with the age at diagnosis of diabetes was not significant. There was also no association of allele X with retinopathy, nephropathy or neuropathy. Only the correlation with BMI was statistically significant. CONCLUSIONS: The DG10S478 variant seems to have no influence on manifestation of diabetes and the development of microvascular complications.

Body weight and oral contraceptives are the most important modulators of serum CRP levels.

BACKGROUND: C-reactive protein (CRP) levels are modulated by endogenous and exogenous factors independently of inflammation. The present study investigated the impact of oral contraceptives, endogenous oestrogens, age, gender, smoking, body mass index (BMI) and lipid levels on CRP concentrations in a healthy collective. METHODS: Highly sensitive CRP, total cholesterol, HDL-cholesterol and LDL-cholesterol levels were measured in 850 blood donors (438 M, 412 F); 227 women in this group used oral contraceptive formulations (OC). Additionally, serum samples from 58 women undergoing in vitro fertilization cycles (IVF) were tested for CRP. Results. The 97.5th percentile of CRP levels of the blood donors was 4.91 mg/L in men, 7.52 mg/L in OC non-users and 11.95 mg/L in OC users. Overweight gives a 2-fold increase of median CRP levels in men and women. The combination of overweight and OC use in women resulted in 6-fold median CRP levels. Age, smoking and lipid levels were influencing factors of lower significance. In IVF patients the elevated oestradiol levels had no influence on CRP concentrations in multivariance analysis. CONCLUSION: The diagnostic and predictive value of CRP levels is most affected by BMI and oral contraceptive use, which suggests the need for further investigations into the role of CRP modulating factors in monitoring infectious diseases.

Improved vascular function upon pioglitazone treatment in type 2 diabetes is not associated with changes in mononuclear NF-kappaB binding activity.

Thiazolidinediones such as pioglitazone have been shown to exert anti-inflammatory effects independent of their insulin sensitizing effects by reducing activation of the proinflammatory transcription factor NF-kappaB in animal models of experimental diabetes. Furthermore, short-term pioglitazone treatment ameliorates endothelial dysfunction in conduit arteries of patients with type 2 diabetes. Since inflammation is supposed to impair flow-mediated vasodilatation, we studied the effects of an 8-week pioglitazone intervention on endothelial function and mononuclear NF-kappaB activation in patients with type 2 diabetes. Twenty patients were included in a randomized, double-blind, placebo-controlled study receiving 30 mg pioglitazone or placebo, respectively. Flow-mediated endothelium dependent vasodilatation (FMD) of the brachial artery, NF-kappaB binding activity in peripheral blood mononuclear cells [pBMC, determined by electrophoretic mobility shift assay (EMSA)] and interleukin-6 (IL-6)-transcription rates (determined by real-time PCR) were measured at study entry and after eight weeks of intervention. Pioglitazone treatment resulted in a significant improvement of FMD (4.3%+/-3.3; p=0.003), while no effect was seen under placebo medication (2.0%+/-2.7; p=0.71). The correction of FMD was neither paralleled by a pioglitazone-dependent reduction in mononuclear NF-kappaB binding activity (DeltaNF-kappaB activity: pioglitazone: 9.2%+/-6.7, p=0.24; placebo: 5.7%+/-19.6; p=0.82) nor in NF-kappaB dependent gene transcription as determined for IL-6 (DeltaIL-6 pioglitazone: +1.8%+/-12.0, p=0.93; placebo: -0.2%+/-9.7; p=0.92). These data demonstrate for the first time that pioglitazone treatment improves endothelial dysfunction in patients with type 2 diabetes without affecting NF-kappaB binding activity and NF-kappaB dependent proinflammatory gene expression in pBMC.

Communication of HIV viral load to guide sexual risk decisions with serodiscordant partners among San Francisco men who have sex with men.

The objective of this study was to estimate frequency and correlates of discussing HIV viral load (VL) with serodiscordant sex partners to guide decisions about sexual activities among men who have sex with men (MSM). We conducted a cross-sectional survey of 573 San Francisco MSM. Among 507 who knew their HIV status, 397 (78%) were familiar with the term 'viral load', and half (n=199) had a serodiscordant partner in the prior year. These 199 respondents (n=130 [65%] HIV-positive; n=69 [35%] HIV-negative) were the focus of this analysis. A majority (n=111, 56%) discussed VL in the prior year with serodiscordant partners specifically to guide decisions about sexual risk behaviour. Discussion was more common among HIV-positive than HIV-negative participants (adjusted odds ratio [AOR], 3.5; 95% confidence interval [CI], 1.6-7.6), and African Americans compared to whites (AOR, 3.7; 95% CI, 1.5-9.5). HIV-negative men who discussed VL were more concerned about becoming infected, but also more willing to engage in risky behaviour with a partner whose VL is undetectable, than men not discussing VL. Some HIV-negative men may be discussing VL to engage in higher risk behaviour upon learning of an HIV-positive partner's undetectable VL. Interventions targeting MSM should explain that while risk of transmission is likely reduced with a low blood plasma VL, it is not necessarily eliminated.

High risk of human immunodeficiency virus in men who have sex with men with herpes simplex virus type 2 in the EXPLORE study.

The relation between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) acquisition was evaluated among 4,295 high-risk, HIV-negative men who have sex with men in an intensive behavioral intervention (colloquially referred to as "EXPLORE") study in the United States from 1999 to 2003. Sexual behavior data were obtained by computer-assisted self-interview, and sera were collected semiannually for HIV and HSV-2 serology. HSV-2 infection was classified as "recent incident" (at the first HSV-2 seropositive visit), "remote incident" (within 24 months of the first positive visit), and "prevalent" (for visits >24 months after the first HSV-2 positive visit). Baseline HSV-2 prevalence was 20.3%. HSV-2 incidence was 1.9 (95% confidence interval (CI): 1.6, 2.2) per 100 person-years; significant risk factors were African-American race, unprotected receptive anal intercourse, an HIV-positive male sex partner, and six or more male partners in the prior 6 months. The behavioral intervention did not reduce HSV-2 acquisition (adjusted hazard ratio (HR) = 1.2, 95% CI: 0.9, 1.6). Overall HIV incidence was 1.9 (95% CI: 1.7, 2.2) per 100 person-years. HIV risk was elevated among men who have sex with men with recent incident HSV-2 (adjusted HR = 3.6, 95% CI: 1.7, 7.8), remote incident HSV-2 (adjusted HR = 1.7, 95% CI: 0.8, 3.3), and prevalent HSV-2 (adjusted HR = 1.5, 95% CI: 1.1, 2.1) infection compared with HSV-2 seronegative participants. HIV intervention strategies targeting HSV-2 prevention and suppression among men who have sex with men should be evaluated.

Methamphetamine and sildenafil (Viagra) use are linked to unprotected receptive and insertive anal sex, respectively, in a sample of men who have sex with men.

OBJECTIVES: There is evidence that methamphetamine and sildenafil (Viagra) use are associated with sexual risk behaviour among men who have sex with men (MSM). We investigated the association of methamphetamine, sildenafil, and other substance use with unprotected receptive and insertive anal sex among MSM by conducting an encounter specific analysis. METHODS: Data were from a cross sectional, community based survey of MSM in San Francisco regarding behaviour during their most recent anal sex encounter. Mulitvariate regression analysed independent associations of specific substance use and demographic variables with unprotected anal sex behaviours. RESULTS: The sample (n = 388) was diverse in race/ethnicity, age, income, education, HIV status, and homosexual/bisexual identification. More than half (53%) reported unprotected anal sex, including insertive (29%) and receptive (37%) during their most recent anal sex encounter; 12% reported unprotected insertive and 17% reported unprotected receptive anal sex with an HIV discordant or unknown partner. Methamphetamine was used by 15% and sildenafil was used by 6% of the men before or during the encounter; 2% used both drugs. In multivariate analysis controlling for demographic factors and other substance use, methamphetamine use was associated with unprotected receptive (odds ratio (OR), 2.03; 95% confidence interval (CI), 1.09 to 3.76) and sildenafil use was associated with unprotected insertive (OR, 6.51; CI, 2.46 to 17.24) anal sex. Effects were stronger with HIV discordant or unknown sex partners specifically. CONCLUSION: Encounter specific associations of methamphetamine and sildenafil use with unprotected receptive and insertive anal sex, respectively, indicate the importance of assessment specificity and tailoring risk reduction efforts to address certain drugs and sexual behavioural roles among MSM.

Haplotype analysis of the SDF-1 (CXCL12) gene in a longitudinal HIV-1/AIDS cohort study.

The stromal-derived factor-1 (SDF-1) chemokine gene encodes the only natural ligand for CXCR4, the coreceptor for the pathogenic X4 HIV-1 strains. A single-nucleotide polymorphism (SNP) in the 3' untranslated region (SDF1-3'A=rs1801157) of SDF-1 was reported to be protective against infection and progression in some, but not other, epidemiological studies. To identify additional alleles that may influence HIV-1 infection and progression to AIDS, nine SNPs (including rs1801157) spanning 20.2 kb in and around the SDF-1 gene were genotyped in over 3000 African American (AA) and European American (EA) participants enrolled in five longitudinal HIV-1/AIDS natural cohort studies. Six or five haplotypes were present at frequencies greater than 5% in AA or EA, respectively. Six of the nine SNPs occur on only one common haplotype (>5%), while the remaining three SNPs were found on multiple haplotypes, suggesting a complex history of recombination. Among EA, rs754618 was associated with an increased risk of infection (OR=1.50, P=0.03), while rs1801157 (=SDF1-3'A) was associated with protection against infection (OR=0.63, P=0.01). In the MACS cohort, rs1801157 was associated with AIDS-87 (RH=0.31, P=0.02) and with death (RH=0.18, P=0.02). Significant associations to a single disease outcome were found for two SNPs and one haplotype in AA.

Mixed lung infection by Legionella pneumophila and Legionella gormanii detected by fluorescent in situ hybridization.

A mixed infection by Legionella pneumophila and a nonpneumophila Legionella species was detected in a lung biopsy specimen obtained from a patient with atypical pneumonia by fluorescent in situ hybridization (FISH). This result was confirmed by polymerase chain reaction (PCR). Sequencing of PCR products confirmed mixed infection by L. pneumophila and L. gormanii. Culture for Legionella spp. was negative and serology showed a rise only in IgG anti- Legionella pneumophila titer. To our knowledge, this is the first report of a mixed infection by L. pneumophila and a non-pneumophila Legionella species detected by FISH. Because FISH is a rapid and culture independent method that detects specific microorganisms in biopsy specimens it is recommended, in particular, for the detection of fastidious bacteria.

Computerized evaluation of mammographic lesions: what diagnostic role does the shape of the individual microcalcifications play compared with the geometry of the cluster?

OBJECTIVE: The objective of this study was to compare the diagnostic role of features reflecting the geometry of clusters with features reflecting the shape of the individual microcalcification in a mammographic computer-aided diagnosis system. MATERIALS AND METHODS: Three hundred twenty-four cases of clustered microcalcifications with biopsy-proven results were digitized at 42-microm resolution and analyzed on a computerized system. The shape factor and number of neighbors were computed for each microcalcification, and the eccentricity of the cluster was computed as well. The shape factor is related to the individual microcalcification; the average number of neighbors and the cluster eccentricity reflect the cluster geometry. Stepwise discriminant analysis was used to evaluate the contribution of the extracted features in predicting malignancy. The performance of a classifier based on the features selected by stepwise discriminant analysis was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: To obtain the best discrimination model, we used stepwise discriminant analysis to select the average number of neighbors and the shape of the individual microcalcification, but excluded cluster eccentricity. A classification scheme assigned the average number of neighbors a weighting factor, which was 1.49 times greater than that assigned to the shape factor of the individual microcalcification. A scheme based only on these two features yielded an ROC curve with an area under the curve (A(z)) of 0.87, indicating a positive predictive value of 61% for 98% sensitivity. CONCLUSION: Computerized analysis permitted calculations reflecting the shape of individual microcalcification and the geometry of clusters of microcalcifications. For the computerized classification scheme studied, the cluster geometry was more effective in differentiating benign from malignant clusters than was the shape of individual microcalcification.

Drug use and sexual risk behavior among gay and bisexual men who attend circuit parties: a venue-based comparison.

CONTEXT: HIV risk behavior among urban gay/bisexual men has recently increased. High-risk sexual activity and drug use may be particularly high during circuit party (CP) weekends, during which gay/bisexual men congregate for social activities and dancing. OBJECTIVES: To compare prevalence of risk behaviors during CP weekends with those during non-CP weekends. DESIGN: Cross-sectional study. PARTICIPANTS: 295 gay/bisexual men from the San Francisco Bay Area. MAIN OUTCOME MEASURES: Drug use and sexual risk behavior during a San Francisco CP weekend, a CP weekend held in another geographic area (distant weekends), and two non-CP weekends. RESULTS: During their most recent distant CP weekend, 80% of participants used methylenedioxymethamphetamine (ecstasy), 66% ketamine, 43% crystal methamphetamines, 29% gamma-hydroxybutyrate or gamma-butyrolactone (GHB/GBL), 14% sildenafil (Viagra), and 12% amyl nitrites (poppers); 53% used four or more drugs. Drug use prevalence was greater during CP than non-CP weekends ( p <.001). Unprotected anal sex with partners of unknown or opposite HIV serostatus was most prevalent during distant CP weekends, reported by 21% of HIV-positive and 9% of HIV-negative participants. In multivariate analysis, predictors of unprotected anal sex with opposite or unknown HIV serostatus partners included being HIV-positive (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.5), and weekend use of crystal methamphetamines (OR 2.4; 95% CI, 1.1-4.9), sildenafil (OR, 3.8; 95% CI, 2.0-7.3), and amyl nitrites (OR, 2.2; 95% CI, 1.3-4.0). CONCLUSIONS: Prevalence of high-risk activity during these weekends suggests significant potential for HIV transmission in this population. Public health programs in communities hosting CPs should aim to reduce rates of drug use and sexual risk behavior among CP participants, especially HIV-positive men.

Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data.

BACKGROUND: Studies relating certain chemokine and chemokine receptor gene alleles with the outcome of HIV-1 infection have yielded inconsistent results. OBJECTIVE: To examine postulated associations of genetic alleles with HIV-1 disease progression. DESIGN: Meta-analysis of individual-patient data. SETTING: 19 prospective cohort studies and case-control studies from the United States, Europe, and Australia. PATIENTS: Patients with HIV-1 infection who were of European or African descent. MEASUREMENTS: Time to AIDS, death, and death after AIDS and HIV-1 RNA level at study entry or soon after seroconversion. Data were combined with fixed-effects and random-effects models. RESULTS: Both the CCR5-Delta32 and CCR2-64I alleles were associated with a decreased risk for progression to AIDS (relative hazard among seroconverters, 0.74 and 0.76, respectively; P = 0.01 for both), a decreased risk for death (relative hazard among seroconverters, 0.64 and 0.74; P < 0.05 for both), and lower HIV-1 RNA levels after seroconversion (difference, -0.18 log(10) copies/mL and -0.14 log(10) copies/mL; P < 0.05 for both). Having the CCR5-Delta32 or CCR2-64I allele had no clear protective effect on the risk for death after development of AIDS. The results were consistent between seroconverters and seroprevalent patients. In contrast, SDF-1 3'A homozygotes showed no decreased risk for AIDS (relative hazard for seroconverters and seroprevalent patients, 0.99 and 1.03, respectively), death (relative hazard, 0.97 and 1.00), or death after development of AIDS (relative hazard, 0.81 and 0.97; P > 0.5 for all). CONCLUSIONS: The CCR5-Delta32 and CCR2-64I alleles had a strong protective effect on progression of HIV-1 infection, but SDF-1 3'A homozygosity carried no such protection.

Homozygous and heterozygous CCR5-Delta32 genotypes are associated with resistance to HIV infection.

OBJECTIVE: To investigate evidence for resistance to HIV-1 infection associated with the heterozygous genotype CCR5-+/Delta32 and with the homozygous genotype CCR5-Delta32/Delta32, which results in a nonfunctional CCR5 receptor. DESIGN: Cohort study of initially HIV-seronegative high-risk individuals from eight different cities. Enrollment data were analyzed to investigate the association of demographic factors and risk behaviors with CCR5 genotypes on the assumption that increased genotype prevalence among persons with histories of longer or more intensive exposure to HIV would indicate HIV resistance associated with that genotype. Longitudinal data were analyzed to investigate the association of HIV seroincidence with CCR5 genotypes. The cohort of 2996 individuals included 1892 men who have sex with men (MSM), 474 male injection drug users (IDUs), 347 women at heterosexual risk, and 283 female IDUs. MEASUREMENTS: CCR5 genotype, HIV serostatus, demographic factors, and risk behaviors during the 6 months before enrollment, followed by measurement of HIV seroincidence during the subsequent 18 months (for men) and 24 months (for women). RESULTS: Forty (1.3%) subjects were homozygous CCR5-Delta32/Delta32 and 387 (12.9%) were heterozygous CCR5-+/Delta32. All but 1 CCR5-Delta32/Delta32 individuals and 51 CCR5-+/Delta32 individuals were Caucasian. Among 1531 Caucasian MSM, CCR5-+/Delta32 individuals were present more frequently (22.3%) among those reporting unprotected receptive anal intercourse than among those not reporting this risk (15.9%) (p =.002), suggesting a selective advantage of the heterozygous genotype. CCR5-+/Delta32 individuals also had a significantly reduced relative risk of HIV seroconversion adjusted for unprotected receptive anal intercourse compared with CCR5-/+ individuals (relative risk = 0.30, 95% confidence interval [CI]: 0.08-0.97). CCR5-Delta32/Delta32 prevalence among Caucasian MSM was significantly associated with age among subjects recruited from high HIV seroprevalence cities (New York City and San Francisco) (odds ratio [OR] for each decade increase in age = 2.57, CI: 1.56-4.21) but not among those recruited from lower HIV prevalence sites (Boston, Chicago, Philadelphia, Seattle, and Providence/Pawtucket, Rhode Island) (OR = 1.20, CI: 0.75-1.89). CONCLUSIONS: Cross-sectional and longitudinal analyses indicated that among high-risk HIV seronegative MSM, CCR5-+/Delta32 and CCR5-Delta32/Delta32 are associated with protection against HIV infection. These findings imply that strategies aimed at reducing susceptibility to HIV infection by blocking CCR5 receptor sites need not seek blockage of all receptor sites to achieve an imperfect but substantial degree of protection.

Cofactors for HIV disease progression in a cohort of homosexual and bisexual men.

To evaluate cofactors for progression of HIV infection, the authors identified 370 men with well-defined seroconversion dates and cofactor data among participants in the San Francisco City Clinic Cohort (SFCCC). Postseroconversion substance use, sexual behavior, and sexually transmitted diseases were assessed using multivariate proportional hazards models. Weekly use of hallucinogens strongly and independently predicted death (relative hazard [RH], 2.59; 95% confidence interval [CI], 1.56-4.28), as well as diagnosis of AIDS; weekly cocaine use also predicted mortality. Receptive anal intercourse with ejaculation was independently associated with mortality risk (RH, 1.45; 95% CI, 1.02-2.04) and AIDS. The associations of accelerated progression with weekly use of recreational drugs and unprotected receptive anal intercourse need to be confirmed in other prospective cohorts.

Primary care physician job satisfaction and turnover.

OBJECTIVE: To examine the relationship of personal characteristics, organizational characteristics, and overall job satisfaction to primary care physician (PCP) turnover. SUBJECTS AND METHODS: A cohort of 507 postresident, nonfederally employed PCPs younger than 45 years of age, who completed their medical training between 1982 and 1985, participated in national surveys in 1987 and 1991. Psychological, economic, and sociological theories and constructs provided a conceptual framework. Primary care physician personal, organizational, and overall job satisfaction variables from 1987 were considered independent variables. Turnover-related responses from 1991 were dependent variables. Bivariate and multivariate analyses were conducted. RESULTS: More than half (55%) of all PCPs in the cohort left at least 1 practice between 1987 and 1991. Twenty percent of the cohort left 2 employers. PCPs dissatisfied in 1987 were 2.38 times more likely to leave (P < .001). Primary care physicians who believed that third-party payer influence would decrease in 5 years were 1.29 times more likely to leave (P < .03). Non-board certified PCPs were 1.3 times more likely to leave (P < .003). Primary care physicians who believed that standardized protocols were overused were 1.18 times more likely to leave (P < .05). Specialty, gender, age, race, and practice setting were not associated with PCP turnover. CONCLUSIONS: Turnover was an important phenomenon among PCPs in this cohort. The results of this study could enable policy makers, managed care organizations, researchers, and others to better understand the relationship between job satisfaction and turnover.