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BackgroundThe predictors of weight gain remain unclear in people with acute and early HIV infection (AEH).MethodsEligible antiretroviral-naïve men diagnosed with AEH from January 1, 2000, to December 31, 2019, were enrolled in an observational cohort study at the University California, San Diego. The study used multivariable mixed-effect linear regression models to analyze differences in the rate of weight gain over time between participants receiving early vs deferred antiretroviral therapy (ART) treatment, low vs high baseline CD4 count and HIV RNA, and different classes of ART.ResultsA total of 463 participants were identified, with mean CD4 cell count of 507 cells/μL and log HIV RNA of 5.0 copies/mL at study entry. There was no difference in the rate of weight gain between participants who did and did not receive ART within 96 weeks of incident HIV infection. Neither a baseline CD4 count of 100 000 copies/mL was a predictor of weight gain. Compared with persons taking non-nucleoside reverse transcriptase inhibitor–based regimens, those who received integrase strand transfer inhibitor (INSTI)–based regimens showed greater weight gain over time.ConclusionsNeither baseline CD4 count and HIV RNA nor early ART was associated with weight change in the first 96 weeks following incident HIV infection. Use of INSTI-based regimens represented a major driver of weight gain in men who initiated ART with relatively higher CD4 cell counts.

Background Ending the human immunodeficiency virus (HIV) epidemic requires knowledge of key drivers of spread of HIV infection. Methods Between 1996 and 2018, 1119 newly and previously diagnosed, therapy-naive persons with HIV (PWH) from San Diego were followed. A genetic distance–based network was inferred using pol sequences, and genetic clusters grew over time through linkage of sequences from newly observed infections. Cox proportional hazards models were used to identify factors associated with the rate of growth. These results were used to predict the impact of a hypothetical intervention targeting PWH with incident infection. Comparison was made to the Centers for Disease Control and Prevention (CDC) Ending the HIV Epidemic (EHE) molecular surveillance strategy, which prioritizes clusters recently linked to all new HIV diagnoses and does not incorporate data on incident infections. Results Overall, 219 genetic linkages to incident infections were identified over a median follow-up of 8.8 years. Incident cluster growth was strongly associated with proportion of PWH in the cluster who themselves had incident infection (hazard ratio, 44.09 [95% confidence interval, 17.09–113.78]). The CDC EHE molecular surveillance strategy identified 11 linkages to incident infections a genetic distance threshold of 0.5%, and 24 linkages at 1.5%. Conclusions Over the past 2 decades, incident infections drove incident HIV cluster growth in San Diego. The current CDC EHE molecular detection and response strategy would not have identified most transmission events arising from those with incident infection in San Diego. Molecular surveillance that includes detection of incident cases will provide a more effective strategy for EHE.

Cytomegalovirus (CMV) almost universally infects persons with HIV (PWH), and it is a driver of persistent inflammation and HIV persistence. The mechanisms underlying the association between CMV (and possibly other herpesviruses) and HIV persistence are unclear. Serially collected blood samples were obtained from men who have sex with men (MSM) who started antiretroviral therapy (ART) within 1 year of their estimated date of HIV infection (EDI). Total CMV and Epstein-Barr virus (EBV) DNA were quantified in peripheral blood mononuclear cells by droplet digital PCR (ddPCR). Deep sequencing of the HIV DNA partial env gene was performed, and the dynamics of viral diversity over time were analyzed in relation to CMV and EBV shedding status. In total, 37 MSM PWH were included and followed for a median of 23 months (IQR, 22 to 28). Participants started ART within a median of 3.1 months (IQR, 1.5 to 6.5) after EDI and remained virally suppressed thereafter. A total of 18 participants (48.6%) were classified as high EBV shedders, while 19 (51.4%) were classified as CMV shedders. In longitudinal analyses, normalized molecular diversity levels tended to increase over time among participants with detectable CMV and high EBV DNA (0.03 ± 0.02, P = 0.08), while they significantly declined among participants with no/low viral shedding (-0.04 ± 0.02, P = 0.047, interaction P

HIV transmission is increased during acute and early HIV (AEH). Rapid antiretroviral therapy may shorten the duration of infectivity. We show rapid antiretroviral therapy in AEH is acceptable and effective, with 69.0% of participants starting ART within 7 days of HIV diagnosis disclosure, and 88.1% achieving suppression by 48 weeks.

Author(s): Choi, Jun Yong; Pond, Sergei L Kosakovsky; Anderson, Christy M; Richman, Douglas D; Smith, Davey M | Abstract: BackgroundInvestigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies.MethodsTo boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus.ResultsThe recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission.ConclusionsBy using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions.

Cannabis use is frequent among people living with human immunodeficiency virus (HIV) and is associated with reduced systemic inflammation. We observed a faster HIV DNA decay during antiretroviral therapy among cannabis users, compared to those with no drug use. No cannabis effect was observed on cellular HIV RNA transcription.

Most people living with HIV (PLWH) are coinfected with cytomegalovirus (CMV). Subclinical CMV replication is associated with immune dysfunction and with increased HIV DNA in antiretroviral therapy (ART)-naive and -suppressed PLWH. To identify immunological mechanisms by which CMV could favor HIV persistence, we analyzed 181 peripheral blood mononuclear cell (PBMC) samples from 64 PLWH starting ART during early HIV infection with subsequent virologic suppression up to 58 months. In each sample, we measured levels of CMV and Epstein-Barr virus (EBV) DNA by droplet digital PCR (ddPCR). We also measured expression of immunological markers for activation (HLA-DR(+) CD38(+)), cycling (Ki-67(+)), degranulation (CD107a(+)), and the immune checkpoint protein PD-1 on CD4(+) and CD8(+) T cell memory subsets. Significant differences in percentages of lymphocyte markers by CMV/EBV shedding were identified using generalized linear mixed-effects models. Overall, CMV DNA was detected at 60/181 time points. At the time of ART initiation, the presence of detectable CMV DNA was associated with increased CD4(+) T cell activation and CD107a expression and with increased CD8(+) T cellular cycling and reduced CD107a expression on CD8(+) T cells. While some effects disappeared during ART, greater CD4(+) T cell activation and reduced CD107a expression on CD8(+) T cells persisted when CMV was present (P

Author(s): Smith, Davey M; Nakazawa, Masato; Freeman, Michael L; Anderson, Christy M; Oliveira, Michelli F; Little, Susan J; Gianella, Sara | Abstract: Background A low CD4/CD8 ratio in human immunodeficiency virus (HIV)-infected individuals is associated with inflammation and higher risk of non-AIDS morbidity and mortality. In this study, we investigated the effect of subclinical cytomegalovirus (CMV) and Epstein-Barr virus (EBV) replication on CD4+ and CD8+ T-cell dynamics when antiretroviral therapy (ART) is started during early infection.Methods We investigated 604 peripheral blood mononuclear cell samples from 108 CMV- and EBV-seropositive HIV-infected men who have sex with men, who started ART within a median of 4 months from their estimated date of infection and were followed for a median of 29.1 months thereafter. Levels of CMV and EBV DNA were measured at each timepoint. Mixed-effects asymptotic regression models were applied to characterize CD4+ and CD8+ T-cell dynamics, and Bayesian hierarchical models were used to quantify individual differences in CMV and EBV DNA replication.Results Higher levels of subclinical CMV replication were associated with lower predicted maximum levels of CD4/CD8 ratio (P l .05), which was driven by higher levels of CD8+ T-cell counts (P l .05), without affecting CD4+ T-cell counts (P g .1). Age was negatively associated with CD4/CD8 levels (P l .05), and this effect was independent of the CMV association (P l .05 for both CMV and age in a multivariate model).Conclusions Subclinical CMV replication in blood cells during early HIV infection and younger age were associated with lower CD4/CD8 ratios during suppressive ART. These findings suggest that active CMV infection in the setting of treated HIV may represent an attractive potential target for therapeutic intervention.

Author(s): Mehta, Sanjay R; Murrell, Ben; Anderson, Christy M; Kosakovsky Pond, Sergei L; Wertheim, Joel O; Young, Jason A; Freitas, Lorri; Richman, Douglas D; Mathews, W Chris; Scheffler, Konrad; Little, Susan J; Smith, Davey M | Abstract: BackgroundBecause recently infected individuals disproportionately contribute to the spread of human immunodeficiency virus (HIV), we evaluated the impact of a primary HIV screening program (the Early Test) implemented in San Diego.MethodsThe Early Test program used combined nucleic acid and serology testing to screen for primary infection targeting local high-risk individuals. Epidemiologic, HIV sequence, and geographic data were obtained from the San Diego County Department of Public Health and the Early Test program. Poisson regression analysis was performed to determine whether the Early Test program was temporally and geographically associated with changes in incident HIV diagnoses. Transmission chains were inferred by phylogenetic analysis of sequence data.ResultsOver time, a decrease in incident HIV diagnoses was observed proportional to the number primary HIV infections diagnosed in each San Diego region (P l .001). Molecular network analyses also showed that transmission chains were more likely to terminate in regions where the program was marketed (P = .002). Although, individuals in these zip codes had infection diagnosed earlier (P = .08), they were not treated earlier (P = .83).ConclusionsThese findings suggests that early HIV diagnoses by this primary infection screening program probably contributed to the observed decrease in new HIV diagnoses in San Diego, and they support the expansion and evaluation of similar programs.

A high seroprevalence of hepatitis A virus (81%) among human immunodeficiency virus–negative high-risk men who have sex with men is likely why this community was largely spared from a recent hepatitis A virus outbreak in San Diego, California.

Implementation of measures to prevent the spread of human immunodeficiency virus (HIV), such as perinatal antiretroviral prophylaxis [1], needle-syringe programs in intravenous drug users (IVDUs) [2], and antiretroviral treatment as prevention [3], are having a dramatic impact on the HIV epidemic [4–6]. The observation that HIV preexposure prophylaxis (PrEP) decreases the risk of HIV infection in clinical trials of high-risk men who have sex with men (MSM), HIV-serodiscordant couples, heterosexual persons in areas of high HIV incidence [7–10] and IVDUs [11] has generated enthusiasm [12]. However, 2 studies of PrEP in women were not promising, with the Female Preexposure Prophylaxis (FEM-PrEP) [13] study requiring an early discontinuation for futility and the Vaginal and Oral Interventions to Control the Epidemic (VOICE) study reporting no effect in the intention-to-treat analyses [14]. The divergent results of PrEP studies are largely attributed to differences in PrEP adherence between studies, but other potential factors (biologic differences or complex sociodemographic issues) have not been evaluated [7]. The divergent results also raise concerns about the feasibility and efficacy of real-world PrEP. To assist clinicians in the implementation of PrEP, the Centers for Disease Control and Prevention (CDC) has published guidance documents detailing how to determine eligibility, begin, follow up, and discontinue PrEP [15, 16] until comprehensive US Public Health Service guidelines are available. The main purpose of this survey was to assess provider opinions, readiness, and current practices of PrEP in the United States and Canada.

Author(s): Green, Nella; Hoenigl, Martin; Chaillon, Antoine; Anderson, Christy M; Kosakovsky Pond, Sergei L; Smith, Davey M; Little, Susan J | Abstract: BackgroundTo examine the yield of HIV partner services provided to persons newly diagnosed with acute and early HIV infection (AEH) in San Diego, United States.DesignObservational cohort study.MethodsThe study investigated the yield (i.e. number of new HIV and AEH diagnoses, genetically linked partnerships and high-risk uninfected partners) of partner services (confidential contact tracing) for individuals with AEH enrolled in the San Diego Primary Infection Resource Consortium 1996-2014.ResultsA total of 107 of 574 persons with AEH (19%; i.e. index cases) provided sufficient information to recruit 119 sex partners. Fifty-seven percent of the 119 recruited partners were HIV infected, and 33% of the 119 were newly HIV diagnosed. Among those newly HIV diagnosed, 36% were diagnosed during AEH. There were no significant demographic or behavioral risk differences between HIV-infected and HIV-uninfected recruited partners. Genetic sequences were available for both index cases and partners in 62 partnerships, of which 61% were genetically linked. Partnerships in which both index case and partner enrolled within 30 days were more likely to yield a new HIV diagnosis (P = 0.01) and to be genetically linked (P l 0.01).ConclusionPartner services for persons with AEH within 30 days of diagnosis represents an effective tool to find HIV-unaware persons, including those with AEH who are at greatest risk of HIV transmission.

OBJECTIVES To further understand the role that chronic viral infections of the male genital tract play on HIV-1 dynamics and replication. DESIGN Retrospective, observational study including 236 paired semen and blood samples collected from 115 recently HIV-1 infected antiretroviral naive men who have sex with men. METHODS In this study, we evaluated the association of seminal HIV-1 shedding to coinfections with seven herpes viruses, blood plasma HIV-1 RNA levels, CD4 T-cell counts, presence of transmitted drug resistance mutations (DRMs) in HIV-1 pol, participants' age and stage of HIV-infection using multivariate generalized estimating equation methods. Associations between herpes virus shedding, seminal HIV-1 levels, number and immune activation of seminal T-cells was also investigated (Mann-Whitney). RESULTS Seminal herpes virus shedding was observed in 75.7% of individuals. Blood HIV-1 RNA levels (P < 0.01) and seminal cytomegalovirus (CMV) and human herpes virus (HHV)-8 levels (P < 0.05) were independent predictors of detectable seminal HIV-1 RNA; higher seminal HIV-1 levels were associated with CMV and Epstein-Barr virus (EBV) seminal shedding, and absence of DRM (P < 0.05). CMV and EBV seminal shedding was associated with higher number of seminal T-lymphocytes, but only presence of seminal CMV DNA was associated with increased immune activation of T-lymphocytes in semen and blood. CONCLUSION Despite high median CD4 T-cells numbers, we found a high frequency of herpes viruses seminal shedding in our cohort. Shedding of CMV, EBV and HHV-8 and absence of DRM were associated with increased frequency of HIV-1 shedding and/or higher levels of HIV-1 RNA in semen, which are likely important cofactors for HIV-1 transmission.

Over three-fourths of human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) have at least one herpesvirus detected in their semen, and cytomegalovirus (CMV) is the most prevalent. The presence of CMV is associated with higher T-cell immune activation and with HIV disease progression in treated and untreated individuals. In this study of 113 antiretroviral (ART)-naive HIV-infected MSM, we found that CMV replication in blood and semen was associated with higher levels of HIV DNA in peripheral blood mononuclear cells. These observations suggest that interventions aimed to reduce CMV replication and, thus, systemic immune activation could decrease the size of the latent HIV reservoir.

Asymptomatic replication of human herpesviruses (HHV) is frequent in HIV-infected men and is associated with increased T-cell activation and HIV disease progression. We hypothesized that the presence of replication of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) (the most frequently detected HHV) might influence HIV DNA decay during antiretroviral therapy (ART). We investigated 607 peripheral blood mononuclear cell (PBMC) samples from 107 CMV-seropositive, HIV-infected men who have sex with men, who started ART within a median of 3 months from their estimated date of infection (EDI) and were monitored for a median of 19 months thereafter. Levels of HIV, CMV, and EBV DNA and cellular HIV RNA were measured by droplet digital PCR (ddPCR) for each time point. Using a general linear mixed-effect regression model, we evaluated associations between the presence of detectable CMV DNA and EBV DNA levels and HIV DNA decay and cellular HIV RNA levels, while adjusting for peak HIV RNA, nadir CD4 + count, CD4/CD8 ratio, CMV IgG levels, time from EDI to ART initiation, time from ART initiation to virologic suppression, detectable CMV DNA pre-ART, and age. The presence of intermittent CMV DNA in PBMC during ART was significantly associated with slower decay of HIV DNA ( P = 0.011) but not with increased cellular HIV RNA transcription or more detectable 2-long terminal repeat circles. Higher levels of EBV DNA were also associated with higher levels of HIV DNA ( P < 0.001) and increased unspliced cellular HIV RNA transcription ( P = 0.010). These observations suggest that replication of HHV may help maintain a larger HIV DNA reservoir, but the underlying mechanisms remain unclear. IMPORTANCE Over three-fourths of HIV-infected men have at least one actively replicating human herpesvirus (HHV) in their mucosal secretions at any one time. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the most common, and although it is often asymptomatic, such CMV and EBV replication is associated with higher levels of immune activation and HIV disease progression. We hypothesized that HHV-associated activation of HIV-infected CD4 + T cells might lead to increased HIV DNA. This study found that detectable CMV in blood cells of HIV-infected men was associated with slower decay of HIV DNA even during antiretroviral therapy (ART) that was started during early HIV infection. Similarly, levels of EBV DNA were associated with higher levels of HIV DNA during ART. If this observation points to a causal pathway, interventions that control CMV and EBV replication may be able to reduce the HIV reservoir, which might be relevant to current HIV cure efforts.

We present methods for estimating five-year birth-cohort-specific trends in smoking behavior for individuals born between 1910 and 1984. We combine cross-sectional survey data on smoking behavior from the National Health Interview Surveys (NHIS) conducted between 1965 and 2001 into a single data set. The cumulative incidence of smoking by year of age and calendar year is constructed for each birth cohort from this data set and the effect of differential mortality on ever smoking prevalence is adjusted by modeling the ever smoking prevalence of each cohort for each survey year and back extrapolating that effect to age 30. Cumulative incidence is then scaled to match the ever smoking prevalence at age 30. Survival analyses generate the cumulative cessation among ever smokers across year of age and calendar year and are used to estimate current smoking prevalence. Data from Substance Abuse and Mental Health Services Administration (SAMHSA) National Survey on Drug Use and Health is used to divide those initiating smoking into quintiles of number of cigarettes smoked per day (CPD) and the mean CPD for each quintile in each calendar year is estimated from the NHIS data. For five-year birth cohorts of white, african-american, Hispanic and all race/ethnicity groupings of males and females born between 1910 and 1984, estimates are provided for prevalence of current and ever smoking, incidence of cessation, incidence of initiation, and the distribution of smoking duration and CPD for each calendar year and each single year of age through the year 1999. We believe that we are the first to provide birth-cohort-specific estimates of smoking behaviors for the U.S. population that include distributions of duration of smoking and number of cigarettes per day. These additional elements substantively enhance the utility of these estimates for estimating lung cancer risks.

Efforts to identify all persons infected with HIV in the United States are driven by the hope that early diagnosis will lower risk behaviors and decrease HIV transmission. Identification of HIV-infected people earlier in the course of their infection with HIV antigen/antibody (Ag/Ab) combination assays (4th-generation HIV assays) should help achieve this goal. We compared HIV RNA nucleic acid test (NAT) results to the results of a 4th-generation Ag/Ab assay (Architect HIV Ag/Ab Combo [HIV Combo] assay; Abbott Diagnostics) in 2,744 HIV antibody-negative samples. Fourteen people with acute HIV infection (HIV antibody negative/NAT positive) were identified; the HIV Combo assay detected nine of these individuals and was falsely negative in the remaining five. All five persons missed by the HIV Combo assay were in the stage of exponential increase in plasma virus associated with acute HIV infection (3, 7, 20, 35, 48). In contrast, most acutely infected persons detected by the HIV Combo assay demonstrated either a plateauing or decreasing plasma viral load. The HIV Combo assay also classified as positive five other samples which were negative by NAT. Taken together, the HIV Combo assay had a sensitivity of 73.7% and a specificity of 99.8%. Using published data, we estimated secondary transmission events had HIV infection in these five individuals remained undiagnosed. Screening of our population with NAT cost more than screening with the HIV Combo assay but achieved new diagnoses that we predict resulted in health care savings that far exceed screening costs. These findings support the use of more sensitive assays, like NAT, in HIV screening of populations with a high prevalence of acute HIV infection.

Background We examine whether the lung cancer risk due to smoking has increased over time. Methods Lung cancer risk equations based on prospective mortality data collected from 1960 to 1972 were applied to 5-year birth-cohort-specific estimates of smoking behaviors among white males to estimate lung cancer mortality rates for U.S. white males from 1960 to 2000. These estimated rates were compared to U.S. white male mortality rates for the same birth cohorts. Results Observed birth-cohort-specific U.S. lung cancer mortality rates are substantially higher than those expected from changes in smoking behaviors, and the proportional difference increases with advancing calendar year. This trend persisted even when the duration term was increased in the risk equation. However, adjusting for changes in cigarette design over time by adding a term for the duration of smoking after 1972 resulted in the predicted rates closely approximating the observed U.S. mortality rates. Conclusion Lung cancer risk estimates observed during the 1960s under predict current lung cancer mortality rates in U.S. white males. Adjustment for the duration of smoking after 1972 results in estimates that reasonably approximate the observed U.S. lung cancer mortality, suggesting that lung cancer risks from smoking are increasing in the United States coincident with changes in cigarette design.

Background Incidence rates for adenocarcinoma of the lung are increasing and are higher in the United States than in many other developed countries. We examine whether these trends may be associated with changes in cigarette design. Methods Lung cancer risk equations based on observations during 1960–1972 from the American Cancer Society Cancer Prevention Study I are applied to 5-year birth cohort–specific estimates of changes in smoking behaviors to predict birth cohort–specific rates of squamous cell carcinoma and adenocarcinoma of the lung among US White men for the period 1973–2000. These expected rates are compared to observed rates for the same birth cohorts of White men in the US Surveillance, Epidemiology and End Results (SEER) data. Results Changes in smoking behaviors over the past several decades adequately explain the changes in squamous cell carcinoma rates observed in the SEER data. However, predicted rates for adenocarcinoma do not match the observed SEER data without inclusion of a term increasing the risk for adenocarcinoma with the duration of smoking after 1965. Conclusion The risk of developing squamous cell carcinoma from smoking appears to have remained stable in the United States over the past several decades; however, the risk of adenocarcinoma has increased substantially in a pattern temporally associated with changes in cigarette design.

Preventing initiation of tobacco product use, promoting cessation of tobacco use, and protecting the public from exposure to second hand smoke are recognised by the World Health organization (WHO) Framework Convention on Tobacco Control (FCTC) and by the WHO Study Group on Tobacco Product Regulation (TobReg) as the most effective approaches to reducing tobacco related morbidity and mortality. However, the FCTC also recognises the need for tobacco product regulation in articles 9 and 10 of the treaty. In order to inform that process TobReg has developed a series of reports that begin to provide a scientific foundation for tobacco product regulation.1–6 This paper summarises a proposal, and the considerations that led to it, developed by a joint International Agency for Research on Cancer (IARC) and WHO working group, and approved by TobReg, which presents performance standards for cigarettes and a strategy to use them to mandate a reduction in the toxicant yields for cigarette smoke. The most common measurements used historically to categorise cigarette smoke have been machine measured tar, nicotine and carbon monoxide (TNCO) yields per cigarette based on the US Federal Trade Commission (FTC)/International Standards Organization (ISO) testing regimen. There is a current scientific consensus that these per cigarette yields do not provide valid estimates of human exposure or of relative human exposure when smoking different brands of cigarettes.1 7–9 Communication of these measures to smokers as estimates of their exposure or risk creates harm by misleading smokers to believe that differences in exposures and risk are likely to occur with switching to cigarette brands with different machine-measured yields. This ongoing harm precludes continued acceptance of current regulatory strategies based on per cigarette machine measured TNCO levels and necessitates development of new regulatory approaches. Machine smoking regimens other than the FTC/ISO regimen …

We investigated whether smoking cessation increased in California after a cigarette manufacturer’s retail price increase and an increase in the state cigarette excise tax. The sample for this study was drawn from the 1996 and 1999 California Tobacco Surveys. The rate of unsuccessful and successful quit attempts and the rate of abstinence were calculated for each month of the 14-month period preceding each survey administration. We combined the monthly rates for both surveys and used multiple regression modeling to test whether the proportion of smokers reporting a quit attempt and the proportion of smokers reporting abstinence increased during the period following the price increases. We included several covariates in our models to control for factors other than the price increases that could account for any increases observed in quit attempts and abstinence. Because smokers recall quits occurring closer to the date of the survey better than quits occurring further back in time, we included a term in the models representing the number of months elapsed between the survey administration and the reported quit. We also included terms in the models representing the months before and after the over-the-counter (OTC) availability of the nicotine patch and nicotine gum in 1996 to control for the increase in smoking cessation observed following the availability of OTC nicotine replacement therapy (NRT). Lastly, in order to control for increased quits made in January as a result of New Year’s resolutions, we included a term in our models for quit attempts and successful quits (abstinence) made during this month. Results of the regression analyses indicated a significantly greater proportion of smokers reported quit attempts (p < 0.05) in the months immediately following the cigarette price increases (after November 1998); however, a significant increase in abstinence was only observed from December 1998 through March 1999 (p < 0.05) relative to abstinence occurring before the price increases.

As part of a retrospective analysis of 616 individuals followed from incident HIV infection for up to 18 years as part of the San Diego Primary Infection Cohort, we found 16 individuals who started antiretroviral therapy (ART) within the first 4 months of infection and subsequently interrupted ART after being virologically suppressed for a median of 1.75 years. No individual maintained sustained virologic control after interruption of ART, even when treatment was started during the earliest stages of HIV infection. Median time to HIV-RNA rebound after ART interruption was 0.9 months (range: 0.2-6.4 months).

Men who have sex with men (MSM) bear the greatest burden of human immunodeficiency virus (HIV) infection in the United States and many other nations [1, 2]. MSM represent a dominant risk group for HIV; however, the risk of HIV infection within this population is not uniform [3–5]. Characterizing and identifying the MSM at greatest risk for incident HIV infection might permit more focused delivery of both prevention resources and selection of appropriate interventions, such as intensive counseling, regular HIV screening with methods that detect acute infection (ie, nucleic acid amplification test [NAAT]), and antiretroviral preexposure prophylaxis (PrEP) [6]. Although there are a number of symptom-based scores correlated with risk of acute and early HIV infection (AEH), few of these scores actually predict HIV acquisition risk [7, 8]. One of these, the Denver HIV risk score, focuses on the overall population at risk for HIV infection [9, 10]. Demographic characteristics such as male sex, younger age, and being an MSM are the main drivers of this score [9]; therefore, it would be difficult to discern the relative risk of incident HIV infection in populations that share some or all of these characteristics (ie, MSM). To date, 2 scores have been developed based on data from MSM repeat HIV testers: the Menza score [5] and the Smith score [11]. Both of these risk scores focus mainly on risk behavior during the 6 months before HIV diagnosis. Each of these scores has issues, however, that may contribute to suboptimal performance in real-world settings. First, there are issues with the derivation and validation cohorts used to estimate these scores. The Menza score focused on HIV acquisition in general (ie, acute and chronic infection at the time of diagnosis) in sexually transmitted infection (STI) clinic patients. Because the population used for development of the score sought HIV testing at a median of every 1.6 years (range, 30 days–6.7 years) [5] the behavior reported for the 6 months before diagnosis may not have included the risk behavior at the time of HIV acquisition. The Smith score was derived using a clinical vaccine trial population (enrolled 1998–1999) [11]. Both of the scores were validated using subjects of Project Explore (a HIV prevention trial conducted between 1999 and 2001 [12]). Thus, both scoring methods relied on behavioral risk data collected more than a decade ago in a clinical trial population that may not accurately represent the behavioral risks associated with HIV acquisition risk in a real-world setting today. Finally, the use of methamphetamine or inhaled nitrites in the prior 6 months is weighted in both scores, whereas other drugs are not [5, 11]. The Menza score weighted the use of methamphetamine or inhaled nitrites as the most important variable (11 points), whereas all other risk variables together accounted for a maximum total of 8 points [5]. The fact that behaviors directly associated with HIV acquisition, such as condomless anal intercourse (1 point), have been weighted as significantly less important restricts the use of the score to settings where methamphetamines and inhaled nitrites are the primary drivers of the HIV epidemic (ie, the score may not be applicable to settings where other drugs such as ketamine, γ-hydroxybutyric acid [GHB], cocaine, or ecstasy are significant drivers of HIV risk). An abbreviated version of the Smith score—with similar limitations (ie, data were collected more than a decade ago in a clinical trial population using behavior reported for the 6 months before diagnosis, with inclusion of methamphetamine but exclusion of other drugs)—is currently recommended as a tool to target PrEP among MSM by the US Public Health Service [13]. It may be possible to derive a more robust model that predicts incident HIV acquisition risk by assessing contemporary risk behaviors reported in the period prior to diagnosis with AEH, not chronic infection. Here we aimed (1) to estimate the risk of AEH among MSM, designated the San Diego Early Test (SDET) score, and (2) to validate the SDET score and compare to the 2 previously published risk scores in a real-world population of MSM who underwent HIV testing between 2008 and 2014.

© 2015 Hoenigl et al. Background: The Center for Disease Control and Prevention recommends that high-risk groups, like sexually active men who have sex with men (MSM), receive HIV testing and counseling at least annually. The objective of this study was to investigate the relationship between voluntary repeat HIV testing and sexual risk behavior in MSM receiving rapid serologic and nucleic acid amplification testing. Methods: We performed a cohort study to analyze reported risk behavior among MSM receiving the "Early Test", a community-based, confidential acute and early HIV infection screening program in San Diego, California, between April 2008 and July 2014. The study included 8,935 MSM receiving 17,333 "Early Tests". A previously published risk behavior score for HIV acquisition in MSM (i.e. Menza score) was chosen as an outcome to assess associations between risk behaviors and number of repeated tests. Results: At baseline, repeat-testers (n = 3,202) reported more male partners and more condomless receptive anal intercourse (CRAI) when compared to single-testers (n = 5,405, all P

Objective and hypothesis: To determine whether a temporal relationship exists between the advertising and sales of low-tar cigarettes. It was hypothesised that increases in the advertising of low-tar cigarettes would precede increases in sales for these cigarettes. Methods: The themes of cigarette advertisements were reviewed and coded for 20 low-tar cigarette brands advertised in 13 widely read magazines in the US between 1960 and 1996. These 20 brands represented most of the low-tar cigarette advertisements and cigarette sales from 1967 to 1996. Cigarette sales data were obtained from the 1994 Maxwell report that summarises all cigarette sales from 1925 to 1990. If the advertisement referred to the low-tar attributes of the cigarette advertised, the advertisement was coded as having a low-tar theme and was included in the analysis. Results: Five different graphical presentations of the relationship between the advertising and sales of the 20 low-tar cigarette brands showed a temporal relationship between low-tar advertising and sales for these brands. This relationship was observed for brands that introduced a low-tar alternative into an existing brand family (eg, Marlboro Light) and for new exclusively low-tar brands (eg, Carlton). Despite large increases in the advertising for the exclusively low-tar brands, sales of these brands remained low relative to sales of the low-tar alternative brands. Conclusions: Increases in print advertising of 20 of the most popular low-tar cigarette brands were followed by increases in sales for these cigarettes. Despite increases in the advertising of exclusively low-tar brands in the mid-1970s and early 1980s, the sales of these brands never matched the sales of the low-tar alternative brands. This suggests that it may have been easier to get smokers to switch to low-tar brands within a brand family compared with entirely new low-tar brands. Over the past 30 years, the marketing of low-tar cigarettes as a healthier alternative to higher-tar cigarettes has resulted in these brands dominating the market, and may have kept concerned smokers from quitting.

California Tobacco Survey respondents were asked the intensity of their cigarette smoking 1 year previously and at the time of the survey. Respondents reported a generally lower smoking intensity at survey time compared with 1 year previously. Multivariable statistical models on the change in smoking intensity in the past year were fitted to assess the effects of low-tar cigarette use, a quit attempt in the past year, smoking intensity 1 year previously, and demographic variables (age, education, income, and race). The most important predictor of change in intensity was the intensity 1 year previously. The next most important predictor was whether a quit attempt had been made in the previous year. The demographic variables also were found to have a significant effect, although their effects were of smaller magnitude. Low-tar cigarette use was not a significant predictor of change in intensity in multivariable analysis. The effect of a quit attempt on the reduction in intensity of smoking suggests that periods of cessation may reduce the intensity of smoking and the level of addiction for several months following relapse. Consequently, it may be important to control for cessation activity in studies comparing exposures from conventional tobacco products to exposures from new products that purport to offer lower harm.

The Food and Drug Administration approved over-the-counter (OTC) sale of nicotine gum and nicotine patches in 1996. We used data from the 1996 California Tobacco Survey to compare the rates of nicotine replacement therapy (NRT) use and smoking abstinence in California for each month during a period immediately preceding and immediately following the OTC availability of nicotine gum and patches. For smokers eligible to report a quit attempt, the proportion making a quit attempt using NRT and the proportion remaining abstinent was calculated for each of the 12 months prior to the survey interview. Multiple regression modeling of quit attempts and abstinence included a term for the number of months between the quit attempt and survey interview and dummy variables for the months before and after the OTC availability of NRT. Results showed a significant increase in the fraction of smokers using the patch (P < 0.01) and gum (P < 0.05) immediately following their availability OTC. There was also a significantly higher proportion of smokers reporting abstinence with gum use (P < 0.01) and a significant increase in reported abstinence with patch use (P < 0.01) during the period of time immediately following the availability of these products without a prescription. The results of this study suggest that removing the prescription status of NRT products resulted in an immediate increase in quit attempts and smoking abstinence with the use of nicotine gum or patches.

Background: Exposure to job-related secondhand smoke represents a significant, but entirely preventable occupational health risk to non-smoking workers. This article examines trends in smoke-free workplace policies in North Carolina. We also examine whether workers comply with such policies. Methods: Data from the Census Bureau’s Current Population Survey were analyzed from 1992 through 2002. Trends for North Carolina workers are compared with workers nationally, and trends are presented by age, race, gender, and type of worker. Results: North Carolina ranks 35th in the proportion of its workforce reporting a smoke-free place of employment. The proportion of workers reporting such a policy doubled between 1992 and 2002. Females were more likely to report a smoke-free work environment (72.0%, CI +/-2.6) than males (61.2%, CI +/-4.6%). Blue-collar (55.6%, CI +/-5.5) and service workers (61.2%, CI +/-8.4), especially males, were less likely to report a smoke-free worksite than white-collar workers (73.4%, CI +/-2.6). Compliance with a smoke-free policy does not appear to be an issue, only 3.2% of workers statewide reported someone had violated their company’s nonsmoking policy. Conclusion: While some progress has been made in North Carolina to protect workers from secondhand smoke, significant disparities exist. Smoke-free policies can make a significant difference in reducing exposure to airborne toxins and their associated diseases, and these protective public health policies have not been shown to reduce business revenues. Much has been done to assure the health and safety of workers through public health policy. However, opportunities to protect North Carolina workers from the health effects of secondhand smoke are limited by a preemptive state law.

Information is lacking on which groups of workers are protected from job-related environmental tobacco smoke. Data from the Census Bureau's Current Population Survey are analyzed for trends in smoke-free workplace policies among 38 major occupations. Data are also analyzed to determine the degree of compliance with such policies. Although over three fourths of white collar workers are covered by smoke-free policies, including 90% of teachers, just 43% of the country's 6.6 million food preparation and service occupations workers benefit from this level of protection. Compliance with workplace restrictions is not a significant human resources issue because only 3.8% of workers reported that someone violated a smoke-free policy in 1999, down from 4.9% in 1996. Protection for workers is increasing, but those in food preparation and service occupations are significantly less protected than others.

Objective: To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission. Design: HIV-1 pol sequence data were analyzed to infer the local transmission network. Methods: We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions. Results: HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p=0.014 and p=0.0455, respectively) and predicted risk of transmission (p,0.0001). Retrospective analysis of antiretroviral therapy (ART) use, and simulations of ART targeted to individuals with the highest TNS, showed significantly reduced network level HIV transmission (p,0.05). Conclusions: Sequence data from an HIV-1 screening program focused on recently infected persons and their social and sexual contacts enabled the characterization of a highly connected transmission network. The network-based risk score (TNS) was highly correlated with transmission risk behaviors and outcomes, and can be used identify and target effective prevention interventions, like ART, to those at a greater risk for HIV-1 transmission.

We present methods for estimating five-year birth-cohort-specific trends in smoking behavior for individuals born between 1910 and 1984. We combine cross-sectional survey data on smoking behavior from the National Health Interview Surveys (NHIS) conducted between 1965 and 2001 into a single data set. The cumulative incidence of smoking by year of age and calendar year is constructed for each birth cohort from this data set and the effect of differential mortality on ever smoking prevalence is adjusted by modeling the ever smoking prevalence of each cohort for each survey year and back extrapolating that effect to age 30. Cumulative incidence is then scaled to match the ever smoking prevalence at age 30. Survival analyses generate the cumulative cessation among ever smokers across year of age and calendar year and are used to estimate current smoking prevalence. Data from Substance Abuse and Mental Health Services Administration (SAMHSA) National Survey on Drug Use and Health is used to divide those initiating smoking into quintiles of number of cigarettes smoked per day (CPD) and the mean CPD for each quintile in each calendar year is estimated from the NHIS data. For five-year birth cohorts of white, african-american, Hispanic and all race/ethnicity groupings of males and females born between 1910 and 1984, estimates are provided for prevalence of current and ever smoking, incidence of cessation, incidence of initiation, and the distribution of smoking duration and CPD for each calendar year and each single year of age through the year 1999. We believe that we are the first to provide birth-cohort-specific estimates of smoking behaviors for the U.S. population that include distributions of duration of smoking and number of cigarettes per day. These additional elements substantively enhance the utility of these estimates for estimating lung cancer risks.

The purpose of this study was to develop life tables by smoking status removing lung cancer as a cause of death. These life tables are inputs to studies that compare the effectiveness of lung cancer treatments or interventions, and provide a way to quantify time until death from causes other than lung cancer. The study combined actuarial and statistical smoothing methods, as well as data from multiple sources, to develop separate life tables by smoking status, birth cohort, by single year of age, and by sex. For current smokers, separate life tables by smoking quintiles were developed based on the average number of cigarettes smoked per day by birth cohort. The end product is the creation of six non-lung cancer life tables for males and six tables for females: five current smoker quintiles and one for never smokers. Tables for former smokers are linear combinations of the appropriate table based on the current smoker quintile prior to quitting smoking and the never smoker probabilities, plus added covariates for the smoking quit age and time since quitting.

Objective To assess factors associated with drug-related harms related to policing among injection drug users (IDUs) in Tijuana, Mexico. Methods IDUs who were over 18 years old and had injected drugs within the last six months were recruited via respondent-driven sampling and underwent questionnaires and testing for HIV (human immunodeficiency virus), syphilis and TB (tuberculosis). Random effects logistic regression was used to simultaneously model factors associated with five drug-related harms related to policing practices in the prior six months (i.e., police led them to rush injections; affected where they bought drugs; affected locations where they used drugs; feared that police will interfere with their drug use; receptive syringe sharing). Results Of 727 IDUs, 85% were male; median age was 38 years. Within the last 6 months, 231 (32%) of IDUs reported that police had led them to rush injections, affected where they bought or used drugs or were very afraid police would interfere with their drug use, or shared syringes. Factors independently associated with drug-related harms related to policing within the last six months included: recent arrest, homelessness, higher frequencies of drug injection, use of methamphetamine, using the local needle exchange program and perceiving a decrease in the purity of at least one drug. Conclusions IDUs who experienced drug-related harms related to policing were those who were most affected by other micro and macro influences in the physical risk environment. Police education programs are needed to ensure that policing practices do not exacerbate risky behaviors or discourage protective behaviors such as needle exchange program use, which undermines the right to health for people who inject drugs.

Background: The potential for negative screening to reduce smoking cessation and long-term abstinence is a concern in lung cancer screening. We examine whether consistently negative results during long-term participation in a lung cancer screening program reduce cessation or increase relapse. Methods: Participants (N = 2,078) in the Early Lung Cancer Action Program received annual screenings and periodic smoking behavior surveys over a follow-up period as long as 12 years. Point abstinence and prolonged abstinence were examined among 730 baseline smokers. Relapse was examined among 1,227 former smokers who quit for 1 year or more at enrollment, 121 recent quitters at enrollment, and 155 baseline smokers who quit during follow-up. Abstinence and relapse for participants with consistently negative computerized tomography scan results were compared with those with non-cancer–positive results using stratified Cox models. Results: Baseline smokers with negative computerized tomography scans had a 28% lower likelihood of achieving point abstinence at one or more follow-up assessments compared with those with positive scans (hazard ratio, 0.72; P < 0.0004), but consistently negative scans were not associated with a lower likelihood of prolonged abstinence. A consistently negative scan was not associated with a higher likelihood of relapse back to smoking for long-term former smokers, recent quitters, or those who quit during follow-up. Conclusions: We did not detect a lower long-term smoking abstinence or increased relapse over a 6-year period of follow-up among individuals participating in a lung cancer screening program who have a consistently negative screening compared with those with a positive, but noncancer, screening result. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3476–83)

Exposure to secondhand smoke is a significant public health problem, causing 38,000 premature deaths annually in nonsmokers. The two major sources of exposure are the home and work. We analyzed occupational data from the Census Bureau's Current Population Survey for smoke-free policy trends among various categories of Texas workers. Nearly three quarters of white collar workers in the state are currently smoke free, but proportionately fewer blue collar and service workers enjoy this level of protection. Hispanics report lower rates of smoke-free policies than whites and African-Americans, and younger workers are less protected than older workers. Smoke-free policies increased 27% from 1992-93 through 1995-96 but only 5% over the next 6 years, indicating a significant slowing in the rate of adoption of such policies. Compliance with a smoke-free policy is not a significant workplace issue in Texas; only 2.7% of workers in 2001-02 reported that someone violated their company's smoke-free policy, down from 5.1% in 1992-93.

Examine trends in home smoking restrictions among employed women not living alone and assess the associations of such restrictions with smoking behaviour.Multivariate logistic regression analysis of major demographic variables and household composition characteristics.128 024 employed female respondents to the Census Bureau's current population survey over the 10 year period 1992 to 2002.The prevalence of smoke free homes has increased significantly over the past decade. This increase was evident across all demographic and household characteristics examined with the greatest rate of increase seen among smoking households. Nearly 90% of households consisting of all never smoking adult members reported having a smoke free home in 2001-02 compared with 22% of households consisting of all smokers. The extent of smoking restrictions in the home was the most powerful determinant of cessation of all the factors examined in the regression model. Odds of becoming a former smoker (any length) and quit for three months or more were seven to eight times greater among those women reporting their homes were smoke free compared with those whose homes permitted smoking anywhere in the home.Smoke free homes were associated with a highly significant increase in quitting (p0.0001). However, at this time it is not clear what proportion of the observed effect can be attributed to living in a smoke free home. None the less, the significantly increased probability of quitting correlated with having a smoke free home found in this analysis, are substantially higher than the odds reported in most workplace studies published to date; additional studies are needed to elucidate this relation.

Exposure to job-related secondhand smoke represents a significant, but entirely preventable occupational health risk to non-smoking workers. This article examines trends in smoke-free workplace policies in North Carolina. We also examine whether workers comply with such policies.Data from the Census Bureau's Current Population Survey were analyzed from 1992 through 2002. Trends for North Carolina workers are compared with workers nationally and trends are presented by age, race, gender, and type of worker.North Carolina ranks 35th in the proportion of its workforce reporting a smoke-free place of employment. The proportion of workers reporting such a policy doubled between 1992 and 2002. Females were more likely to reporta smoke-free work environment (72.0%, CI +/- 2.6) than males (61.2%, CI +/- 4.6%). Blue-collar (55.6%, CI +/- 5.5) and service workers (61.2%, CI +/- 8.4), especially males, were less likely to report a smoke-free worksite than white-collar workers (73.4%, CI +/- 2.6). Compliance with a smoke-free policy does not appear to be an issue, only 3.2% of workers statewide reported someone had violated their company's nonsmoking policyWhile some progress has been made in North Carolina to protect workers from secondhand smoke, significant disparities exist. Smoke-free policies can make a significant difference in reducing exposure to airborne toxins and their associated diseases, and these protective public health policies have not been shown to reduce business revenues. Much has been done to assure the health and safety of workers through public health policy However, opportunities to protect North Carolina workers from the health effects of secondhand smoke are limited by a preemptive state law.

This report summarizes trends in Arkansas to protect workers from the documented harm caused by secondhand smoke. We also examined whether employees comply with smoke-free policies.While considerable progress has been made to protect workers from secondhand smoke, Arkansas workers report significantly lower rates of smoke-free policies than workers nationally and ranked 46th among the states in this important area of occupational health in 2001-02. Blue-collar and service workers in the state lag significantly behind their white-collar counterparts and men report lower rates of smoke-free policies than women. Once implemented, however, compliance with a smoke-free policy is nearly universal among working Arkansans.

OBJECTIVE—To define US national sex specific rates of smoking initiation among Hispanic, non-Hispanic white, and African American adolescents aged 12-17 years for each calendar year from 1940 through 1992. METHODS—Adult survey data from the tobacco use supplement of the Current Population Survey in 1992-93 and 1995-96 were used to reconstruct the age at which individuals began to smoke and the calendar year in which they were that age. From these data, the number of individuals who began a calendar year as never smokers and who were aged 12-17 years during that year could be estimated and formed the denominator of the initiation rate. The number of these individuals who reported taking up smoking during that year formed the numerator of the initiation rate. RESULTS—Initiation rates among male adolescents in each of the three racial/ethnic groups have declined since 1945. However, since 1983, initiation rates among male adolescents overall have increased. Non-Hispanic white male adolescents generally initiated cigarette smoking at higher rates than Hispanic or African American male adolescents. Initiation rates among Hispanic male adolescents have not been statistically different from initiation rates among African American male adolescents. From 1978 to 1982, initiation rates among Hispanic and African American male adolescents experienced a sharp decline, and the rate of decline was steeper than that experienced by non-Hispanic white male adolescents. Initiation rates among female adolescents have increased since 1940, catching up to male adolescent initiation rates by the mid 1970s. Initiation rates among female adolescents appeared to level off or increased slightly again from the mid 1980s to 1990. Non-Hispanic white female adolescents generally initiate cigarette smoking at higher rates than Hispanic or African American female adolescents. Initiation rates among non-Hispanic white and African American female adolescents equalled the initiation rates of their male counterparts by the mid 1970s, but initiation rates among Hispanic female adolescents did not overlap with initiation rates of Hispanic male adolescents until 1990. From 1975 to 1980, initiation rates among African American female adolescents decreased sharply, but, unlike initiation rates among the two other ethnic groups, rates continued to decline from 1984 to 1990. CONCLUSIONS—Different patterns of increasing and decreasing smoking initiation among sex and ethnic adolescent groups suggest the effect of varying social and cultural influences. These findings support the importance of including ethnic factors in studies of smoking behaviour. Keywords: smoking initiation; adolescents; ethnic groups

Veterans of the Persian Gulf War have complained of ill health, with diverse symptoms, since the war's end. We report here on postwar reproductive outcomes among spouses of male Gulf War veterans, compared with those among spouses of same-era male nondeployed veterans. From 1996, a probability-based sample of 8,915 deployed and nondeployed male military veterans aged 18-33 and married were mailed a reproductive health survey. A total of 2,716 Gulf War veterans and 2,169 nondeployed veterans returned the questionnaires, for a participation rate of 62.0 percent. Adjusting for age, race/ethnicity, educational attainment, military component, and pre-1991 reproductive outcomes, no statistically significant differences were found in the odds of reporting singleton or multiple births, ectopic pregnancies, or stillbirths. Male Gulf War veterans did report increased odds that their partners had exerienced a miscarriage in the first 2 years following the Gulf War.

Veterans of the Persian Gulf War have complained of ill health, with diverse symptoms, since the war's end. We report here on postwar reproductive outcomes among female Gulf War veterans, compared with those in 1991-era nondeployed veterans. Since 1996, a stratified, probability-based sample of 8,251 deployed and nondeployed female military veterans, aged 18-33 years and married, has been mailed a reproductive health survey. A total of 2,349 Gulf War Veterans and 2,507 nondeployed veterans returned the questionnaires, for a participation rate of 71.7 percent. Adjusted forage, race/ethnicity, educational attainment, military component, and pre-1991 reproductive outcomes, no statistically significant differences between female Gulf War veterans and nondeployed veterans were identified in the odds of reporting a live, normal full-term, macros macrosomic (birth weight >/- 4,000 g) or a low birth weight (< 2,500 g) birth, or among stillbirths, ectopic pregnancies, miscarriages, and sub fertility. No differences were noted among twin or higher multiple births. Although symptoms of reproductive ill health have been reported by veterans of the 1991 Gulf War, this large-scale and broad-based survey of the reproductive health of 1991-era US military veterans survey suggests that the reproductive health of female Gulf War veterans was unaffected by their deployment to the Gulf War.