Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1.

Background: Investigations 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. Methods: To 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. Results: The 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. Conclusions: By 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.

Replication of Human Herpesviruses Is Associated with Higher HIV DNA Levels during Antiretroviral Therapy Started at Early Phases of HIV Infection.

UNLABELLED: 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.

Asymptomatic CMV Replication During Early Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower CD4/CD8 Ratio During HIV Treatment.

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 < .05), which was driven by higher levels of CD8+ T-cell counts (P < .05), without affecting CD4+ T-cell counts (P > .1). Age was negatively associated with CD4/CD8 levels (P < .05), and this effect was independent of the CMV association (P < .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.

Using HIV Sequence and Epidemiologic Data to Assess the Effect of Self-referral Testing for Acute HIV Infection on Incident Diagnoses in San Diego, California.

BACKGROUND: Because 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. METHODS: The 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. RESULTS: Over time, a decrease in incident HIV diagnoses was observed proportional to the number primary HIV infections diagnosed in each San Diego region (P < .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). CONCLUSIONS: These 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.

Development and validation of the San Diego Early Test Score to predict acute and early HIV infection risk in men who have sex with men.

BACKGROUND: Although men who have sex with men (MSM) represent a dominant risk group for human immunodeficiency virus (HIV), the risk of HIV infection within this population is not uniform. The objective of this study was to develop and validate a score to estimate incident HIV infection risk. METHODS: Adult MSM who were tested for acute and early HIV (AEH) between 2008 and 2014 were retrospectively randomized 2:1 to a derivation and validation dataset, respectively. Using the derivation dataset, each predictor associated with an AEH outcome in the multivariate prediction model was assigned a point value that corresponded to its odds ratio. The score was validated on the validation dataset using C-statistics. RESULTS: Data collected at a single HIV testing encounter from 8326 unique MSM were analyzed, including 200 with AEH (2.4%). Four risk behavior variables were significantly associated with an AEH diagnosis (ie, incident infection) in multivariable analysis and were used to derive the San Diego Early Test (SDET) score: condomless receptive anal intercourse (CRAI) with an HIV-positive MSM (3 points), the combination of CRAI plus ≥5 male partners (3 points), ≥10 male partners (2 points), and diagnosis of bacterial sexually transmitted infection (2 points)-all as reported for the prior 12 months. The C-statistic for this risk score was >0.7 in both data sets. CONCLUSIONS: The SDET risk score may help to prioritize resources and target interventions, such as preexposure prophylaxis, to MSM at greatest risk of acquiring HIV infection. The SDET risk score is deployed as a freely available tool at http://sdet.ucsd.edu.

Repeat HIV-testing is associated with an increase in behavioral risk among men who have sex with men: a cohort study.

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 <0.001). In 2,457 repeat testers there was a strong association observed between repeated HIV tests obtained and increased risk behavior, with number of male partners, CRAI with high risk persons, non-injection stimulant drug use, and sexually transmitted infections all increasing between the first and last test. There was also a linear increase of risk (i.e. high Menza scores) with number of tests up to the 17th test. In the multivariable mixed effects model, more HIV tests (OR = 1.18 for each doubling of the number of tests, P <0.001) and younger age (OR = 0.95 per 5-year increase, P = 0.006) had significant associations with high Menza scores. CONCLUSIONS: This study found that the highest risk individuals for acquiring HIV (e.g. candidates for antiretroviral pre-exposure prophylaxis) can be identified by their testing patterns. Future studies should delineate causation versus association to improve prevention messages delivered to repeat testers during HIV testing and counseling sessions.

Are we prepped for preexposure prophylaxis (PrEP)? Provider opinions on the real-world use of PrEP in the United States and Canada.

BACKGROUND: Preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (Truvada) has demonstrated efficacy in placebo-controlled clinical trials involving men who have sex with men, high-risk heterosexuals, serodiscordant couples, and intravenous drug users. To assist in the real-world provision of PrEP, the Centers for Disease Control and Prevention (CDC) has released guidance documents for PrEP use. METHODS: Adult infectious disease physicians were surveyed about their opinions and current practices of PrEP through the Emerging Infections Network (EIN). Geographic information systems analysis was used to map out provider responses across the United States. RESULTS: Of 1175 EIN members across the country, 573 (48.8%) responded to the survey. A majority of clinicians supported PrEP but only 9% had actually provided it. Despite CDC guidance, PrEP practices were variable and clinicians reported many barriers to its real-world provision. CONCLUSIONS: The majority of adult infectious disease physicians across the United States and Canada support PrEP but have vast differences of opinion and practice, despite the existence of CDC guidance documents. The success of real-world PrEP will likely require multifaceted programs addressing barriers to its provision and will be assisted with the development of comprehensive guidelines for real-world PrEP.

Cytomegalovirus DNA in semen and blood is associated with higher levels of proviral HIV DNA.

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.

Assessing the reliability of the CD4 depletion model in the presence of Ending the HIV Epidemic initiatives.

BACKGROUND: Accurate estimates of HIV incidence are necessary to monitor progress towards Ending the HIV Epidemic (EHE) initiative targets (90% decline by 2030). U.S. incidence estimates are derived from a CD4 depletion model (CD4 model). We performed simulation-based analyses to investigate the ability of this model to estimate HIV incidence when implementing EHE interventions that have the potential to shorten the duration between HIV infection and diagnosis (diagnosis delay). METHODS: Our simulation study evaluates the impact of three parameters on the accuracy of incidence estimates derived from the CD4 model: rate of HIV incidence decline, length of diagnosis delay, and sensitivity of using CD4 + cell counts to identify new infections (recency error). We model HIV incidence and diagnoses after the implementation of a theoretical prevention intervention and compare HIV incidence estimates derived from the CD4 model to simulated incidence. RESULTS: Theoretical interventions that shortened the diagnosis delay (10-50%) result in overestimation of HIV incidence by the CD4 model (10-92%) in the first year and by more than 10% for the first 6 years after implementation of the intervention. Changes in the rate of HIV incidence decline and the presence of recency error had minimal impact on the accuracy of incidence estimates derived from the CD4 model. CONCLUSION: In the setting of EHE interventions to identify persons with HIV earlier during infection, the CD4 model overestimates HIV incidence. Alternative methods to estimate incidence based on objective measures of incidence are needed to assess and monitor EHE interventions.

Cost savings associated with testing of antibodies, antigens, and nucleic acids for diagnosis of acute HIV infection.

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.

Chapter 2: Birth-cohort-specific estimates of smoking behaviors for the U.S. population.

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.

Chapter 3: Cohort life tables by smoking status, removing lung cancer as a cause of death.

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 before quitting smoking and the never smoker probabilities, plus added covariates for the smoking quit age and time since quitting.

Do changes in cigarette design influence the rise in adenocarcinoma of the lung?

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.

Has the lung cancer risk from smoking increased over the last fifty years?

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.

Factors associated with drug-related harms related to policing in Tijuana, Mexico.

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.

Pandemic (H1N1) 2009 Surveillance in Marginalized Populations, Tijuana, Mexico.

To detect early cases of pandemic (H1N1) 2009 infection, in 2009 we surveyed 303 persons from marginalized populations of drug users, sex workers, and homeless persons in Tijuana, Mexico. Six confirmed cases of pandemic (H1N1) 2009 were detected, and the use of rapid, mobile influenza testing was demonstrated.

Increased HIV-1 superinfection risk in carriers of specific human leukocyte antigen alleles.

OBJECTIVE: The aim of this study was to characterize the demographic, behavioural, clinical and immunogenetic determinants of HIV-1 superinfection in a high-risk cohort of MSM. DESIGN: A retrospective cohort study of prospectively followed MSM. METHODS: Ninety-eight MSM with acute or early HIV-1 monoinfection were followed for a median of 15.6 months. Demographic and human leukocyte antigen (HLA) genotype data were collected at enrolment. Sexual behaviour, clinical and the infection status (monoinfection or superinfection) data were recorded at each visit (at enrolment and thereafter at a median of 4.2-month intervals). HIV-1 superinfection risk was determined by Cox regression and Kaplan-Meier survival analysis. RESULTS: Ten individuals (10.2%) had superinfection during follow-up. Cox regression did not show significantly increased superinfection risk for individuals with an increased amount of condomless anal intercourse, lower CD4 T-cell count or higher viral load, but higher number of sexual contacts demonstrated a trend towards significance [hazard ratio, 4.74; 95% confidence interval (95% CI), 0.87-25.97; P = 0.073]. HLA-A*29 (hazard ratio, 4.10; 95% CI, 0.88-14.76; P = 0.069), HLA-B*35 (hazard ratio, 4.64; 95% CI, 1.33-18.17; P = 0.017), HLA-C*04 (hazard ratio, 5.30; 95% CI, 1.51-20.77; P = 0.010), HLA-C*16 (hazard ratio, 4.05; 95% CI, 0.87-14.62; P = 0.071), HLA-DRB1*07 (hazard ratio, 3.29; 95% CI, 0.94-12.90; P = 0.062) and HLA-DRB1*08 (hazard ratio, 15.37; 95% CI, 2.11-79.80; P = 0.011) were associated with an increased risk of superinfection at α = 0.10, whereas HLA-DRB1*11 was associated with decreased superinfection risk (hazard ratio, 0.13; 95% CI, 0.00-1.03; P = 0.054). CONCLUSION: HLA genes may, in part, elucidate the genetic basis of differential superinfection risk, and provide important information for the development of efficient prevention and treatment strategies of HIV-1 superinfection.

Partner services in adults with acute and early HIV infection.

BACKGROUND: To examine the yield of HIV partner services provided to persons newly diagnosed with acute and early HIV infection (AEH) in San Diego, United States. DESIGN: Observational cohort study. METHODS: The 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. RESULTS: A 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 < 0.01). CONCLUSION: Partner 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.

Association between home smoking restrictions and changes in smoking behaviour among employed women.

STUDY OBJECTIVE: Examine trends in home smoking restrictions among employed women not living alone and assess the associations of such restrictions with smoking behaviour. DESIGN: Multivariate logistic regression analysis of major demographic variables and household composition characteristics. STUDY PARTICIPANTS: 128 024 employed female respondents to the Census Bureau's current population survey over the 10 year period 1992 to 2002. MAIN RESULTS: 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. CONCLUSIONS: Smoke free homes were associated with a highly significant increase in quitting (p<0.0001). 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.

The temporal relationship between advertising and sales of low-tar cigarettes.

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.