Ilene Brill

Women at risk of HIV / STD: the importance of male partners as barriers to condom use.

Womens perceptions of power in their relationship with their main partner, control over condom use, concerns about potential partner retribution, condom requests, and condom use were assessed by interviewing a group of women attending two urban public clinics for sexually transmitted diseases in Alabama. Only 5% reported that they had no control over condom use by their partner. Fears of catastrophic partner reactions to condom use requests (sexual coercion, abuse, or abandonment) and experiences of partner objections were also uncommon. Women did not perceive themselves to be powerless. Inconsistent condom use was associated with wanting condom use but not asking and with perceived consequences of relationship loss, however, most power-related measures, including physical abuse, were not related to condom use in the 30 days prior to the interview.

Human Leukocyte Antigen Class I Genotypes in Relation to Heterosexual HIV Type 1 Transmission within Discordant Couples

Differences in immune control of HIV-1 infection are often attributable to the highly variable HLA class I molecules that present viral epitopes to CTL. In our immunogenetic analyses of 429 HIV-1 discordant Zambian couples (infected index partners paired with cohabiting seronegative partners), several HLA class I variants in index partners were associated with contrasting rates and incidence of HIV-1 transmission within a 12-year study period. In particular, A*3601 on the A*36-Cw*04-B*53 haplotype was the most unfavorable marker of HIV-1 transmission by index partners, while Cw*1801 (primarily on the A*30-Cw*18-B*57 haplotype) was the most favorable, irrespective of the direction of transmission (male to female or female to male) and other commonly recognized cofactors of infection, including age and GUI. The same HLA markers were further associated with contrasting viral load levels in index partners, but they had no clear impact on HIV-1 acquisition by the seronegative partners. Thus, HLA class I gene products not only mediate HIV-1 pathogenesis and evolution but also influence heterosexual HIV-1 transmission.

Enrollment and retention of HIV discordant couples in Lusaka, Zambia.

Background:Biased enrollment and attrition compromise the power of clinical trials and limit generalizability of findings. We identify predictors of enrollment and retention for HIV-discordant couples enrolled in prospective studies in Zambia. Principal Findings:A total of 1995 discordant couples were invited to enroll. Predictors of nonenrollment, loss to follow-up, and missed appointments were evaluated using multivariate models. M+F− couples were more likely to be eligible and to enroll and less likely to be lost to follow-up than F+M− couples. Substantial losses to follow-up occurred between testing and enrollment (21.3% of M+F− and 28.1% of F+M−) and between enrollment and the first follow-up visit (24.9% of M+F− and 30.5% of F+M−). Among M+F− and F+M− couples, residence far from the clinic, younger age, and womens age at first intercourse ≤17 years were predictive of attrition. No income, ≤2 lifetime sex partners, no history of sexually transmitted infection in women, and recent extramarital contact in their male partners predicted attrition in F+M− couples. Conclusions:Discordant couples are critical to observational studies and clinical trials to prevent male-to-female and female-to-male transmission. Retention biases must be taken into account during analysis. Run-in designs that delay randomization may improve retention in clinical trials.

Brain tumors among electronics industry workers.

We evaluated the relation between work experience in the United States operations of an electronics company and brain tumor mortality, focusing on video display terminal (VDT) development jobs. Subjects were 149 brain tumor cases and 591 matched controls selected from a company registry of all employees dying between 1975 and 1989. Company databases and interviews with company personnel constituted the basis for work histories, including information on whether subjects had held VDT development jobs. Subjects who worked at plants with hardware or VDT development operations had slightly but imprecisely elevated odds ratios (OR). The study found no meaningful association between VDT development work and brain tumor mortality. Other results included an elevated OR for 10 or more years of employment in engineering/technical jobs [OR = 1.7; 95% confidence interval (CI) = 1.0–3.0] or in programming jobs (OR = 2.8; 95% CI = 1.1–7.0). The OR for glioma for all subjects who had accrued 5 years of programming work 10 years before the cases death was 3.9 (95% CI = 1.2–12.4). These associations were limited in large part to one of four division groups. Also, only male programmers experienced an elevated OR. These patterns indicate that the associations may be due to chance, although unidentified causal exposures present in a subset of engineering/technical and programming jobs cannot be ruled out.

Human Leukocyte Antigens and HIV Type 1 Viral Load in Early and Chronic Infection: Predominance of Evolving Relationships

Background During untreated, chronic HIV-1 infection, plasma viral load (VL) is a relatively stable quantitative trait that has clinical and epidemiological implications. Immunogenetic research has established various human genetic factors, especially human leukocyte antigen (HLA) variants, as independent determinants of VL set-point. Methodology/Principal Findings To identify and clarify HLA alleles that are associated with either transient or durable immune control of HIV-1 infection, we evaluated the relationships of HLA class I and class II alleles with VL among 563 seroprevalent Zambians (SPs) who were seropositive at enrollment and 221 seroconverters (SCs) who became seropositive during quarterly follow-up visits. After statistical adjustments for non-genetic factors (sex and age), two unfavorable alleles (A*3601 and DRB1*0102) were independently associated with high VL in SPs (p<0.01) but not in SCs. In contrast, favorable HLA variants, mainly A*74, B*13, B*57 (or Cw*18), and one HLA-A and HLA-C combination (A*30+Cw*03), dominated in SCs; their independent associations with low VL were reflected in regression beta estimates that ranged from −0.47±0.23 to −0.92±0.32 log10 in SCs (p<0.05). Except for Cw*18, all favorable variants had diminishing or vanishing association with VL in SPs (p≤0.86). Conclusions/Significance Overall, each of the three HLA class I genes had at least one allele that might contribute to effective immune control, especially during the early course of HIV-1 infection. These observations can provide a useful framework for ongoing analyses of viral mutations induced by protective immune responses.

Cigarette smoking and risk of histological subtypes of epithelial ovarian cancer in the EPIC cohort study

New data regarding a positive association between smoking and risk of epithelial ovarian cancer (EOC), especially the mucinous tumor type, has started to emerge. The purpose of this study was to examine the association between different measures of smoking exposures and subtypes of EOC in a large cohort of women from 10 European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort is a multicenter prospective study initiated in 1992. The questionnaires included data about dietary, lifestyle, and health factors. Information about cigarette smoking was collected from individuals in all participating countries. We used Cox proportional hazard regression models to estimate hazard ratio (HR) of EOC overall and serous, mucinous, and endometroid histological subtypes, with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables. Altogether 836 incident EOC cases were identified among 326,831 women. The tumors were classified as 400 serous, 83 mucinous, 80 endometroid, 35 clear cell, and 238 unspecified. Compared with never smokers, current smokers had a significantly increased risk for mucinous tumors [HR = 1.85 (95% CI 1.08–3.16)] and those smoking more than 10 cigarettes per day had a doubling in risk [HR = 2.25(95% CI 1.26–4.03)] as did those who had smoked less than 15 pack‐years of cigarettes [HR = 2.18 (95% CI 1.07–4.43)]. The results from the EPIC study add further evidence that smoking increases risk of mucinous ovarian cancer and support the notion that the effect of smoking varies according to histological subtype.

A case-control study of leukemia among petroleum workers.

This case-control study evaluates the relationship between leukemia and the work histories of active and retired employees of a large petroleum company. The study includes 69 cases with leukemia and 284 matched controls. Employment in production-related work in the oil and gas division was associated with myelogenous leukemia (odds ratio [OR]=2.0, 95% confidence interval [CI]=.97 to 4.2) and particularly with acute myelogenous leukemia (OR=2.8, 95% CI=1.1 to 7.3). The association with acute myelogenous leukemia was strongest for subjects in the highest tertile (32+ years) of duration of employment in oil- and gas production-related work (OR=8.7, 95 % CI=2.0 to 37), and there was a consistent trend of increasing ORs with increasing duration of employment (P= .01). No clear association was observed for refining division work and leukemia. This is the first epidemiologic study reporting a positive association between oil and gas field work and acute myelogenous leukemia.

Risk Factors for Incident Herpes Simplex Type 2 Virus Infection Among Women Attending a Sexually Transmitted Disease Clinic

Objectives: To estimate the incidence of herpes simplex type 2 virus (HSV-2) infection, to identify risk factors for its acquisition, and to assess the protective effect of condoms. Study Design: Prospective study of 293 HSV-2 seronegative women, aged 18 to 35 years, attending a sexually transmitted disease clinic in Alabama from 1992 to 1995. Results: Incidence of HSV-2 infection was 20.5 per 100 woman-years [95% confidence interval (CI), 13.1–30.5]. Young women (18–20 years) had a significantly higher risk of incident HSV-2 infection [adjusted hazard ratio (HR), 2.8; 95% CI, 1.3–6.4] than older women. Women diagnosed with prevalent or incident bacterial vaginosis had a higher incidence of HSV-2 infection than those who were not so diagnosed (adjusted HR, 2.4; 95% CI, 1.1–5.6). No significant protective effect was observed for consistent (100%) condom use without breakage and slippage against HSV-2 acquisition (adjusted HR, 0.8; 95% CI, 0.2–2.3). Conclusion: Acquisition of HSV-2 infection among study participants was higher than previous estimates for adult female sexually transmitted disease clinic attendees, and no protective effect for condoms was demonstrated. The high incidence of HSV-2 infection with its potential for adverse health consequences emphasizes the need for better prevention strategies.

Disparate associations of HLA class I markers with HIV-1 acquisition and control of viremia in an African population.

Background Acquisition of human immunodeficiency virus type 1 (HIV-1) infection is mediated by a combination of characteristics of the infectious and the susceptible member of a transmission pair, including human behavioral and genetic factors, as well as viral fitness and tropism. Here we report on the impact of established and potential new HLA class I determinants of heterosexual HIV-1 acquisition in the HIV-1-exposed seronegative (HESN) partners of serodiscordant Zambian couples. Methodology/Principal Findings We assessed the relationships of behavioral and clinically documented risk factors, index partner viral load, and host genetic markers to HIV-1 transmission among 568 cohabiting couples followed for at least nine months. We genotyped subjects for three classical HLA class I genes known to influence immune control of HIV-1 infection. From 1995 to December 2006, 240 HESNs seroconverted and 328 remained seronegative. In Cox proportional hazards models, HLA-A*68:02 and the B*42-C*17 haplotype in HESN partners were significantly and independently associated with faster HIV-1 acquisition (relative hazards = 1.57 and 1.55; p = 0.007 and 0.013, respectively) after controlling for other previously established contributing factors in the index partner (viral load and specific class I alleles), in the HESN partner (age, gender), or in the couple (behavioral and clinical risk score). Few if any previously implicated class I markers were associated here with the rate of acquiring infection. Conclusions/Significance A few HLA class I markers showed modest effects on acquisition of HIV-1 subtype C infection in HESN partners of discordant Zambian couples. However, the striking disparity between those few markers and the more numerous, different markers found to determine HIV-1 disease course makes it highly unlikely that, whatever the influence of class I variation on the rate of infection, the mechanism mediating that phenomenon is identical to that involved in disease control.

Association of chemokine receptor gene (CCR2-CCR5) haplotypes with acquisition and control of HIV-1 infection in Zambians

BackgroundPolymorphisms in chemokine (C-C motif) receptors 2 and 5 genes (CCR2 and CCR5) have been associated with HIV-1 infection and disease progression. We investigated the impact of CCR2-CCR5 haplotypes on HIV-1 viral load (VL) and heterosexual transmission in an African cohort. Between 1995 and 2006, cohabiting Zambian couples discordant for HIV-1 (index seropositive and HIV-1 exposed seronegative {HESN}) were monitored prospectively to determine the role of host genetic factors in HIV-1 control and heterosexual transmission. Genotyping for eight CCR2 and CCR5 variants resolved nine previously recognized haplotypes. By regression and survival analytic techniques, controlling for non-genetic factors, we estimated the effects of these haplotypic variants on a) index partner VL, b) seroconverter VL, c) HIV-1 transmission by index partners, d) HIV-1 acquisition by HESN partners.ResultsAmong 567 couples, 240 virologically linked transmission events had occurred through 2006. HHF*2 homozygosity was associated with significantly lower VL in seroconverters (mean beta = -0.58, log10P = 0.027) and the HHD/HHE diplotype was associated with significantly higher VL in the seroconverters (mean beta = 0.54, log10P = 0.014) adjusted for age and gender in multivariable model. HHD/HHE was associated with more rapid acquisition of infection by the HESNs (HR = 2.0, 95% CI = 1.20-3.43, P = 0.008), after adjustments for index partner VL and the presence of genital ulcer or inflammation in either partner in Cox multivariable models. The HHD/HHE effect was stronger in exposed females (HR = 2.1, 95% CI = 1.14-3.95, P = 0.018).ConclusionsAmong Zambian discordant couples, HIV-1 coreceptor gene haplotypes and diplotypes appear to modulate HIV-1 VL in seroconverters and alter the rate of HIV-1 acquisition by HESNs. These associations replicate or resemble findings reported in other African and European populations.