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ObjectivesWe investigated whether the effect of smoking on the incidence of smoking-related cancers differs by HIV-infection status, if sex modifies the impact of risk factors for smoking-related cancers, and the sex-specific attributable risk of smoking on cancer incidence.DesignData from two large prospective studies in the United States were analyzed: 6789 men in the Multicenter AIDS Cohort Study from 1984 through 2018 and 4423 women in the Women's Interagency HIV Study from 1994 through 2018.MethodsIncidence rates, relative risks, and adjusted population attributable fractions (PAFs) were calculated for smoking-related cancers.ResultsDuring study follow-up, there were 214 incident smoking-related cancers in the men and 192 in the women. The age-adjusted incidence ratess for smoking-related cancers were higher in the women (392/100 000) than for the men (198/100 000; P

Objectives Inaccuracies in cause-of-death information in death certificates can reduce the validity of national death statistics and result in poor targeting of resources to reduce morbidity and mortality in people with HIV. Our objective was to measure the sensitivity, specificity, and agreement between multiple causes of deaths from death certificates obtained from the National Death Index (NDI) and causes determined by expert physician review. Methods Physician specialists determined the cause of death using information collected from the medical records of 50 randomly selected HIV-infected people who died in San Francisco from July 1, 2016, through May 31, 2017. Using expert review as the gold standard, we measured sensitivity, specificity, and agreement. Results The NDI had a sensitivity of 53.9% and a specificity of 66.7% for HIV deaths. The NDI had a moderate sensitivity for non–AIDS-related infectious diseases and non–AIDS-related cancers (70.6% and 75.0%, respectively) and high specificity for these causes (100.0% and 94.7%, respectively). The NDI had low sensitivity and high specificity for substance abuse (27.3% and 100.0%, respectively), heart disease (58.3% and 86.8%, respectively), hepatitis B/C (33.3% and 97.7%, respectively), and mental illness (50.0% and 97.8%, respectively). The measure of agreement between expert review and the NDI was lowest for HIV (κ = 0.20); moderate for heart disease (κ = 0.45) and hepatitis B/C (κ = 0.40); high for non–AIDS-related infectious diseases (κ = 0.76) and non–AIDS-related cancers (κ = 0.72); and low for all other causes of death (κ < 0.35). Conclusions Our findings support education and training of health care providers to improve the accuracy of cause-of-death information on death certificates.

Background Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART). Methods We evaluated AIDS-free, ART-naive PLWH during 1996–2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350–500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject’s age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses. Results Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37–.86), AIDS-defining cancers (HR 0.23; 95% CI, .11–.49), any virus-related cancer (HR 0.30; 95% CI, .16–.54), Kaposi sarcoma (HR 0.25; 95% CI, .10–.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06–.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference −1.6; 95% CI, −2.8, −.5). Conclusions Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.

Background Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH). Methods We enrolled n = 865 WLWH (323 from the Women’s Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics). All participants underwent Pap and oncHPV testing, including HPV16/18-genotyping. WIHS WLWH who tested oncHPV[+] or had cytologic atypical squamous cells of undetermined significance or worse (ASC-US+) underwent colposcopy, as did a random 21% of WLWH who were oncHPV[−]/Pap[−] (controls). Most participants additionally underwent p16/Ki-67 immunocytochemistry. Results Mean age was 46 years, median CD4 was 592 cells/µL, 95% used antiretroviral therapy. Seventy WLWH had histologically-determined cervical intraepithelial neoplasia grade 2 or greater (CIN-2+), of which 33 were defined as precancer (ie, [i] CIN-3+ or [ii] CIN-2 if concurrent with cytologic high grade squamous intraepithelial lesions [HSILs]). PHS had 87% sensitivity (Se) for precancer, 9% positive predictive value (PPV), and a 35% colposcopy referral rate (Colpo). “PHS with reflex HPV16/18-genotyping and Pap testing” had 84% Se, 16% PPV, 30% Colpo. PHS with only HPV16/18-genotyping had 24% Colpo. “Concurrent oncHPV and Pap Testing” (Co-Testing) had 91% Se, 12% PPV, 40% Colpo. p16/Ki-67 immunochemistry had the highest PPV, 20%, but 13% specimen inadequacy. Conclusions PHS with reflex HPV16/18-genotyping had fewer unnecessary colposcopies and (if confirmed) could be a potential alternative to Co-Testing in WLWH.

ObjectiveRecent studies reported a lower human papillomavirus 16 (HPV16) prevalence in cervical precancer among African American than Caucasian women in the general population. We assessed this relationship in women with HIV.DesignWomen living with or at risk for HIV in the Women's Interagency HIV Study were followed semi-annually with Pap tests, colposcopy/histology (if indicated), and collection of cervicovaginal lavage samples for HPV testing by PCR. Racial and ethnic groups were defined using genomic Ancestry Informative Markers (AIMs).ResultsAmong 175 cases of cervical intraepithelial neoplasia 3 or worse (CIN-3+), 154 were diagnosed in women with HIV. African American (27%) and Hispanic (37%) cases were significantly less likely than Caucasian (62%) women to test positive for HPV16 (P = 0.01). In multivariate logistic regression models, these associations remained significant for African Americans (odds ratio = 0.13; 95% confidence interval (CI) 0.04-0.44; P = 0.001) but not Hispanics, after controlling for HIV status, CD4 count, history of AIDS, age, smoking, and sexual behavior. Limiting the analysis to women with HIV did not change the findings.ConclusionHPV16 prevalence is lower in African American compared with Caucasian women with HIV and cervical precancer, independent of immune status. Future studies to determine why these racial differences exist are warranted, and whether there are similar associations between race and invasive cervical cancer in women with HIV. Further, HPV types not covered by quadrivalent and bivalent vaccines may play an especially important role in cervical precancer among HIV-positive African American women, a possible advantage to using nonavalent HPV vaccine in this population.

Integrase inhibitor–based (INSTI) antiretroviral therapy (ART) regimens are preferred for most people with HIV (PWH). We examined factors associated with INSTI use among PWH in San Francisco who started ART in 2009–2016. PWH who experienced homelessness were less likely, and older PWH were more likely, to use an INSTI.

Despite elevated mortality in people with HIV (PWH) using drugs, drug-related deaths are poorly characterized. Among 6764 drug-related deaths, methamphetamine was more common in PWH than others. One in 4 deaths in PWH involved acute infection. Combatting mortality in PWH who use drugs should include stimulant-specific and infection prevention efforts.

Infection by human papillomavirus (HPV) type 16, the most oncogenic HPV type, was found to be the least affected by HIV-status and CD4 count of any of the approximately 13 oncogenic HPV types. This relative independence from host immune status has been interpreted as evidence that HPV16 may have an innate ability to avoid the effects of immunosurveillance. However, the impact of immune status on other individual HPV types has not been carefully assessed. We studied type-specific HPV infection in a cohort of 2,470 HIV-positive (HIV[+]) and 895 HIV-negative (HIV[−]) women. Semi-annually collected cervicovaginal lavages were tested for >40 HPV types. HPV type-specific prevalence ratios (PRs), incidence and clearance hazard ratios (HRs), were calculated by contrasting HPV types detected in HIV[+] women with CD4 < 200 to HIV[−] women. HPV71 and HPV16 prevalence had the weakest associations with HIV-status/CD4 count of any HPV, according to PRs. No correlations between PRs and HPV phylogeny or oncogenicity were observed. Instead, higher HPV type-specific prevalence in HIV[−] women correlated with lower PRs (ρ = −0.59; p = 0.0001). An alternative (quadratic model) statistical approach (P(HIV+) = a*P(HIV−) + b*P(HIV−)(2); R(2) = 0.894) found similar associations (p = 0.0005). In summary, the most prevalent HPV types in HIV[−] women were the types most independent from host immune status. These results suggest that common HPV types in HIV[−] women may have a greater ability to avoid immune surveillance than other types, which may help explain why they are common.

For people living with HIV, lack of adherence to antiretroviral therapy (ART) is a serious problem and frequently results in HIV disease progression. Reasons for non-adherence include concomitant psychosocial health conditions – also known as syndemic conditions – such symptoms of depression or posttraumatic stress disorder (PTSD), past physical or sexual abuse, intimate partner violence (IPV), stimulant use, and binge drinking. The aim of this study was to investigate the association between syndemic conditions and medication adherence. The sample included 281 older men living with HIV who have sex with men (MSM). The study period was December 2012–July 2016. We observed the following syndemic conditions significantly decreased medication adherence: symptoms of depression (p = .008), PTSD (p = .002), and stimulant use (p < .0001). Past physical or sexual abuse, IPV, and binge drinking were not significantly associated with decreased medication adherence. The findings suggest that syndemic conditions may impact medication adherence in older MSM living with HIV.

Background People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. Methods We studied 102 777 PLWH during 1996–2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Results Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for Conclusions Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

Objective:The authors assessed the association of physical function, social variables, functional status, and psychiatric co-morbidity with cognitive function among older HIV-infected adults.Design:From 2012–2014, a cross-sectional study was conducted among HIV-infected patients ages 50 or older who underwent comprehensive clinical geriatric assessment.Setting:Two San Francisco HIV clinics.Participants:359 HIV-infected patients age 50 years or olderMeasurementsUnadjusted and adjusted Poisson regression measured prevalence ratios and 95% confidence intervals for demographic, functional and psychiatric variables and their association with cognitive impairment using a Montreal Cognitive Assessment (MoCA) score < 26 as reflective of cognitive impairment.ResultsThirty-four percent of participants had a MoCA score of < 26. In unadjusted analyses, the following variables were significantly associated with an abnormal MoCA score: born female, not identifying as homosexual, non-white race, high school or less educational attainment, annual income < $10,000, tobacco use, slower gait speed, reported problems with balance, and poor social support. In subsequent adjusted analysis, the following variables were significantly associated with an abnormal MoCA score: not identifying as homosexual, non-white race, longer 4-meter walk time, and poor social support. Psychiatric symptoms of depressive, anxiety, and post-traumatic stress disorders did not correlate with abnormal MoCA scores.Conclusions:Cognitive impairment remains common in older HIV-infected patients. Counter to expectations, co-morbid psychiatric symptoms were not associated with cognitive impairment, suggesting that cognitive impairment in this sample may be due to neurocognitive disorders, not due to other psychiatric illness. The other conditions associated with cognitive impairment in this sample may warrant separate clinical and social interventions to optimize patient outcomes.

BACKGROUND Cutaneous melanoma incidence may be modestly elevated in people with HIV (PWH) vs. people without HIV. However, little is known about the relationship of immunosuppression, HIV replication, and antiretroviral therapy (ART) with melanoma risk. METHODS PWH of white race in the North American AIDS Cohort Collaboration on Research and Design were included. A standardized incidence ratio was calculated comparing risk with the white general population, standardizing by age, sex, and calendar period. Associations between melanoma incidence and current, lagged, and cumulative measures of CD4 count, HIV RNA level, and ART use were estimated with Cox regression, adjusting for established risk factors such as age and annual residential ultraviolet B (UVB) exposure. RESULTS Eighty melanomas were diagnosed among 33,934 white PWH (incidence = 40.75 per 100,000 person-years). Incidence was not elevated compared with the general population [standardized incidence ratio = 1.15, 95% confidence interval (95% CI) = 0.91 to 1.43]. Higher melanoma incidence was associated with older age [adjusted hazard ratio (aHR) per decade increase = 1.50, 95% CI = 1.20 to 1.89] and higher UVB exposure (aHR for exposure ≥35 vs.

Background Early virologic suppression (VS) after human immunodeficiency virus (HIV) infection improves individual health outcomes and decreases onward transmission. In San Francisco, immediate antiretroviral therapy (ART) at HIV diagnosis was piloted in 2013–2014 and expanded citywide in 2015 in a rapid start initiative to link all new diagnoses to care within 5 days and start ART at the first care visit. Methods HIV providers and linkage navigators were trained on a rapid start protocol with sites caring for vulnerable populations prioritized. Dates of HIV diagnosis, first care visit, ART initiation, and VS were abstracted from the San Francisco Department of Public Health HIV surveillance registry. Results During 2013–2017, among 1354 new HIV diagnoses in San Francisco, median days from diagnosis to first VS decreased from 145 to 76 (48%; P Conclusions During a multisector initiative to optimize ART initiation, median time from diagnosis to VS decreased by nearly half. Immediate ART at care initiation was achieved across many, but not all, populations, and was associated with improved suppression rates.

Background:San Francisco has launched interventions to reduce new human immunodeficiency virus (HIV) infections and HIV-associated morbidity and mortality during the San Francisco "Getting to Zero" era. We measured recent changes in HIV care indicators to assess the success of these interventions. Methods:San Francisco residents with newly diagnosed HIV infection, diagnosed from 2009 to 2014, were included. We measured temporal changes from HIV diagnosis to (1) linkage to care in within ≤3 months, (2) initiation of antiretroviral therapy (ART) within ≤12 months, (3) viral suppression within ≤12 months, (4) development of AIDS within ≤3 months, (5) death within ≤12 months, and (6) retention in care 6-12 months after linkage. Kaplan-Meier analyses stratified by year of HIV diagnosis measured time from diagnosis to linkage, ART initiation, viral suppression, AIDS, and death. Results:Overall, the number of new diagnoses declined from 473 in 2009 to 329 in 2014. The proportion of new diagnoses among men (P = .005), Latinos and Asian/Pacific Islanders (P = .02), and men who have sex with men (P = .003) increased. ART initiation and viral suppression ≤12 months after diagnosis increased (P < .001), while the proportion with AIDS diagnosed ≤3 months after HIV diagnosis declined (P < .001). Time to ART initiation and time to viral suppression were significantly shorter in more recent years of diagnosis (P < .001). Time from HIV to AIDS diagnosis was significantly longer in more recent years (P < .001). Retention in care did not significantly change. Conclusions:In San Francisco new HIV diagnoses have declined and HIV care indicators have improved during the Getting to Zero era. Continued success requires attention to vulnerable populations and monitoring to adjust programmatic priorities.

Kaposi sarcoma (KS) remains common among HIV-infected persons. To better understand KS etiology and to help target prevention efforts, we comprehensively examined a variety of CD4 T-cell count and HIV-1 RNA viral load (VL) measures, as well as antiretroviral therapy (ART) use, to determine independent predictors of KS risk.North American AIDS Cohort Collaboration on Research and Design.We followed HIV-infected persons during 1996-2009 from 18 cohorts. We used time-updated Cox regression to model relationships between KS risk and recent, lagged, trajectory, and cumulative CD4 count or VL measures, as well as ART use. We used Akaike's information criterion and global P values to derive a final model.In separate models, the relationship between each measure and KS risk was highly significant (P0.0001). Our final mutually adjusted model included recent CD4 count [hazard ratio (HR) for50 vs. ≥500 cells/μL = 12.4; 95% confidence interval (CI): 6.5 to 23.8], recent VL (HR for ≥100,000 vs. ≤500 copies/mL = 3.8; 95% CI: 2.0 to 7.3), and cumulative (time-weighted mean) VL (HR for ≥100,000 vs. ≤500 copies/mL = 2.5; 95% CI: 1.0 to 5.9). Each P-trend was0.0001. After adjusting for these measures, we did not detect an independent association between ART use and KS risk.Our results suggested a multifactorial etiology for KS, with early and late phases of development. The cumulative VL effect suggested that controlling HIV replication promptly after HIV diagnosis is important for KS prevention. We observed no evidence for direct anti-KS activity of ART, independent of CD4 count and VL.

To estimate the incidence of invasive cervical cancer (ICC) across up to 21 years of follow-up among women with human immunodeficiency virus (HIV) and to compare it to that among HIV-uninfected women, we reviewed ICC diagnoses from a 20-year multi-site U.S. cohort study of HIV infected and uninfected women who had Pap testing every 6 months. Incidence rates were calculated and compared to those in HIV-negative women. Incidence ratios standardized to age-, sex-, race-, and calendar-year specific population rates were calculated. After a median follow-up of 12.3 years, four ICCs were confirmed in HIV seropositive women, only one in the last 10 years of observation, and none in seronegative women. The ICC incidence rate did not differ significantly by HIV status (HIV seronegative: 0/100,000 person-years vs. HIV seropositive: 19.5/100,000 person-years; p = 0.53). The standardized incidence ratio for the HIV-infected WIHS participants was 3.31 (95% CI: 0.90, 8.47; p = 0.07). Although marginally more common in women without HIV, for those with HIV in a prevention program, ICC does not emerge as a major threat as women age.

ObjectiveSan Francisco, California, has experienced a 44% reduction in new HIV diagnoses since 2013 supported by its 'Getting to Zero' initiative; however, the age-adjusted mortality rate in people with HIV (PWH) has not decreased. We sought to identify factors associated with death among PWH in San Francisco.DesignPopulation-based incidence-density case-control study.MethodsAmong PWH in the San Francisco HIV surveillance registry, a random sample of 48 decedents from 1 July 2016 to 31 May 2017 were each matched to two to three controls who were alive at the date of death (108 controls matched on age and time since diagnosis). Covariates included demographics, substance use, housing status, medical conditions, and care indicators from the study population. We used matched-pair conditional logistic regression to examine factors associated with mortality.ResultsOf the 156 PWH in the study, 14% were African-American, 14% Latino, and 8% female sex. In adjusted analysis, factors associated with higher odds of death included: homelessness at HIV diagnosis [adjusted odds ratio (AOR) = 27.4; 95% confidence interval (CI) = 3.0-552.1], prior-year IDU (AOR = 10.2; 95% CI = 1.7-128.5), prior-year tobacco use (AOR = 7.2; 95% CI = 1.7-46.9), being off antiretroviral therapy at any point in the prior year (AOR = 6.8; 95% CI = 1.1-71.4), and being unpartnered vs. married/partnered (AOR = 4.7; 95% CI = 1.3-22.0).ConclusionPeople homeless at HIV diagnosis had 27-fold higher odds of death compared with those with housing; substance use and retention on antiretroviral therapy in the prior year are other important intervenable factors. New strategies to address these barriers, and continued investment in supportive housing and substance use treatment, are needed.

BACKGROUND The comparative effectiveness of pre- and post-exposure prophylaxis (PrEP and PEP) for men who have sex with men (MSM) is unclear. SETTING We conducted a case-control study of MSM who were initially HIV-uninfected during September 1, 2012-June 30, 2016 at San Francisco's only municipal sexually transmitted diseases (STDs) clinic. METHODS Each case was matched with up to 3 controls based on age, baseline visit date, and follow-up time. The primary dependent variable was HIV seroconversion; the primary independent variable was exposure to PrEP, PEP, or neither. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. RESULTS Of 638 MSM (161 cases and 477 controls), 137 reported ever taking PrEP, 98 reported taking PEP-only, and 403 took neither. PrEP takers had more non-HIV sexually transmitted diseases during the analysis (72.3% vs. 55.1% vs. 42.4% P < 0.01) and were more likely to report receptive anal sex in the past 3 months (86.5% vs. 80.4% vs. 73.0%; P < 0.01). In the adjusted model, PrEP was associated with lower odds of HIV seroconversion (odds ratio 0.24; 95% confidence interval: 0.13 to 0.46) while PEP use had no effect on HIV acquisition compared with taking neither. CONCLUSIONS MSM who ever used PrEP demonstrated equal or higher sexual risk compared with those using neither PrEP nor PEP but had 76% lower odds of HIV seroconversion. MSM who used PEP but never PrEP were no less likely to seroconvert than those using neither. MSM should be offered PrEP. PEP users with ongoing risk of HIV infection should be connected to PrEP after PEP.

BackgroundResearch is needed to better understand relations between immunosuppression and HIV viraemia and risk for non-Hodgkin lymphoma, a common cancer in people living with HIV. We aimed to identify key CD4 count and HIV RNA (viral load) predictors of risk for non-Hodgkin lymphoma, overall and by subtype.MethodsWe studied people living with HIV during 1996-2014 from 21 Canadian and US cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. To determine key independent predictors of risk for non-Hodgkin lymphoma, we assessed associations with time-updated recent, past, cumulative, and nadir or peak measures of CD4 count and viral load, using demographics-adjusted, cohort-stratified Cox models, and we compared models using Akaike's information criterion.FindingsOf 102 131 people living with HIV during the study period, 712 people developed non-Hodgkin lymphoma. The key independent predictors of risk for overall non-Hodgkin lymphoma were recent CD4 count (ie, lagged by 6 months

Background Monitoring cancer risk among HIV-infected people in the modern antiretroviral therapy (ART) era is critical given their elevated risk for many cancers and prolonged survival with immunosuppression, ART exposure, and aging. Our study described cancer risk in HIV-infected people in the United States relative to the general population. Methods Utilizing data from linked population-based HIV and cancer registries (nine areas; 1996–2012), we calculated standardized incidence ratios (SIRs). We tested SIR differences by AIDS status and over time using Poisson regression. Findings Among 448,258 HIV-infected people, risk was elevated (p

Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer., International Agency for Research on Cancer

Background: HIV-positive women are at substantial risk of HPV-associated cervical neoplasia caused by high-risk (HR) HPVs. Methylation of the HPV genome is associated with cervical intraepithelial neoplasia grade 3 (CIN3) in HIV-negative women, yet it is unknown whether this holds true for HIV-positive women. Methods: We designed a case–control study within the Women's Interagency HIV Study (WIHS) cohort comparing HIV-positive CIN3 cases (N = 72) to HIV-positive controls without detectable CIN2+. The unit of analysis and matching was HPV-type infection. Cases with ≥2 HR-HPV types (N = 23; 32%) had a separate control for each HR-HPV type. We developed and utilized next-generation sequencing (NGS) methylation assays for 12 different HR-HPVs, focusing on CpG sites in the L1/L2 regions. Results: Significant case–control differences in individual CpG site methylation levels were observed for multiple alpha-9 (HPV16/31/35/58) and alpha-7 HPV (HPV18/39/45) types, based on dichotomization of tertile levels (T3 vs. T1 and T2). Analyses combining homologous CpG sites [e.g., HPV16-L1-5608/HPV31-L1-5521/HPV35-L2L1-5570; OR = 7.28; 95% confidence interval (CI): 2.75–19.3], and (e.g., HPV18-L1-7062/HPV45-L1-7066; OR = 6.94; 95% CI: 1.23–39.3) were significant in separate case–control comparisons. In cases with multiple HR-HPVs, we tested and confirmed the hypothesis that one HR-HPV type would have higher methylation than other types detected, consistent with there being a single HR-HPV causally related to a lesion. Conclusions: CIN3 is associated with elevated L1/L2 CpG methylation levels in HIV-positive women. Impact: HPV DNA CpG methylation is a promising triage option in HIV-positive women testing positive for HR-HPV types and provides risk attribution in women with multiple HPV type infections.

Summary Background Cancer survivors are at increased risk for subsequent primary cancers. People living with HIV are at increased risk for AIDS-defining and non-AIDS-defining cancers, but little is known about their risk of first versus second primary cancers. We identified first and second primary cancers that occurred in above population expected numbers among people diagnosed with HIV in San Francisco, and compared first and second cancer incidence across five time periods that corresponded to important advances in antiretroviral therapy. Methods In this population-based study, we used the San Francisco HIV/AIDS case registry to identify people aged 16 years and older who were diagnosed with HIV/AIDS in San Francisco (CA, USA) between Jan 1, 1990, and Dec 31, 2010. We computer-matched records from the registry with the California Cancer Registry to identify primary cancers diagnosed between Jan 1, 1985, and Dec 31, 2013. We calculated year, age, sex, and race adjusted standardised incidence ratios with exact 95% CIs and trends in incidence of first and second AIDS-defining and non-AIDS-defining cancers from 1985 to 2013. Findings Of the 22 623 people diagnosed with HIV between Jan 1, 1990, and Dec 31, 2010, we identified 5655 incident primary cancers. We excluded 48 cancers with invalid cancer sequence numbers and 1062 in-situ anal cancers, leaving 4545 incident primary cancers, comprising 4144 first primary cancers, 372 second primary cancers, 26 third primary cancers, and three fourth or later primary cancers. First primary cancer standardised incidence ratios were elevated for Kaposi sarcoma (127, 95% CI 121–132), non-Hodgkin lymphoma (17·2, 16·1–18·4), invasive cervical cancer (8·0, 4·1–11·9), anal cancer (46·7, 39·7–53·6), vulvar cancer (13·3, 6·1–20·6), Hodgkin's lymphoma (10·4, 8·4–12·5), eye and orbit cancer (4·2, 1·4–6·9), lip cancer (3·8, 1·3–6·2), penile cancer (3·8, 1·4–6·1), liver cancer (3·0, 2·3–3·7), miscellaneous cancer (2·3, 1·7–3·0), testicular cancer (2·0, 1·4–2·6), tongue cancer (1·9, 1·1–2·7), and lung cancer (1·3, 95% CI 1·1–1·6). Second primary cancer risks were increased for Kaposi sarcoma (28·0, 95% CI 20·2–35·9), anal cancer (17·0, 10·2–23·8), non-Hodgkin lymphoma (11·1, 9·3–12·8), Hodgkin's lymphoma (5·4, 1·1–9·7), and liver cancer (3·6, 1·4–5·8). We observed lower first primary cancer standardised incidence ratios for prostate cancer (0·6, 95% CI 0·5–0·7), colon cancer (0·6, 0·4–0·8), and pancreatic cancer (0·6, 0·3–1·0), and lower second primary cancer standardised incidence ratios for testicular cancer (0·3, 0·0–0·9), kidney cancer (0·4, 0·0–0·9), and prostate cancer (0·6, 0·2–0·9). First and second primary AIDS-defining cancer incidence declined, and second primary non-AIDS-defining cancer incidence increased over time. Interpretation Because of an increased risk for both first and second primary cancers, enhanced cancer prevention, screening, and treatment efforts are needed for people living with HIV both before and after initial cancer diagnosis. Funding University of California San Francisco and US Centers for Disease Control and Prevention.

The increased life expectancy among HIV-infected persons treated with combination antiretroviral therapy (ART), risk behaviors, and co-morbidities associated with ART place HIV-infected persons at risk for non-HIV-related causes of death. We used the San Francisco HIV/AIDS registry to identify deaths that occurred from January 1996 through December 2011. Temporal trends in AIDS- and non-AIDS-related mortality rates, the proportion of underlying and contributory causes of death, and the ratio of observed deaths in the study population to expected number of deaths among California men aged 20-79 (standardized mortality ratio [SMR]) of underlying causes of death were examined. A total of 5338 deaths were identified. The annual AIDS-related death rate (per 100 deaths) declined from 10.8 in 1996 to 0.9 in 2011 (p0.0001), while the annual death rate from non-AIDS-related causes declined from 2.1 in 1996 to 0.9 in 2011 (p0.0001). The proportion of deaths due to all types of heart disease combined, all non-AIDS cancers combined, mental disorders resulting from substance abuse, drug overdose, suicide and chronic obstructive pulmonary disease increased significantly over time. The SMRs for liver diseased decreased significantly over time but remained elevated. Our data highlight the importance of age-related causes of death as well as deaths from causes that are, at least in part, preventable.

Background Antiretroviral therapy (ART) has reduced AIDS-defining cancer (ADC) mortality, but its effect on non-AIDS-defining cancer (NADC) mortality is unclear. To help inform cancer prevention and screening, we evaluated trends in NADC mortality among people with AIDS (PWA) in the ART era. Methods This retrospective cohort study analyzed AIDS surveillance data, including causes of death from death certificates, for PWA in San Francisco who died in 1996–2013. Proportional mortality ratios (PMRs), and year, age, race, sex-adjusted standardized mortality ratios (SMRs) were calculated for 1996–1999, 2000–2005, and 2006–2013, corresponding to advances in ART. Results The study included 5822 deceased PWA of whom 90% were male and 68% were aged 35–54 at time of death. Over time, the PMRs significantly decreased for ADCs (2.6%, 1.4%, 1.2%) and increased for NADCs (4.3%, 7.0%, 12.3%). For all years combined (1996–2013) and compared to the California population, significantly elevated SMRs were observed for these cancers: all NADCs combined (2.1), anal (58.4), Hodgkin lymphoma (10.5), liver (5.2), lung/larynx (3.0), rectal (5.2), and tongue (4.7). Over time, the SMRs for liver cancer (SMR 19.8, 11.2, 5.0) significantly decreased while the SMRs remained significantly elevated over population levels for anal (SMR 123, 48.2, 45.5), liver (SMR 19.8, 11.2, 5.0), and lung/larynx cancer (SMR 5.3, 4.7, 3.6). Conclusion A decline in ADC PMRs and increase in NADC PMRs represent a shift in the cancer burden, likely due to ART use. Moreover, given their elevated SMRs, anal, liver, and lung/larynx cancer remain targets for improved cancer prevention, screening, and treatment.

Little is known about food insecurity and its association with geriatric outcomes in older people living with HIV (PLWH). This was a cross-sectional study of 230 HIV-infected patients aged 50 and older recruited in December 2012 through June 2016. Poisson logistic regression models estimated the prevalence ratio (PR) and 95% confidence intervals (CI) for the association between food insecurity and the following geriatric outcomes: frailty, physical health and function, social support, mental health and cognition, and behavioral health. 157 (68%) participants were food secure, 35 (15%) had low food security, and 38 (17%) had very low food security. After adjusting the analyses for other significant covariates, at risk alcohol or drug use (PR = 3.14; 95% CI 1.75–5.64), being sedentary (PR = 3.30; 95% CI 1.09–10.00) depressive symptoms (PR = 1.77; 95% CI 1.13–2.76), and dependent instrumental activities of daily living (PR = 2.46; 95% CI 1.13–5.36) were significantly associated with very low food security. These results highlight a need for structural HIV interventions that incorporate targeted food assistance strategies for older PLWH.

Smoking increases the risk of morbidity and mortality and is particularly harmful to HIV-infected people.To explore smoking trends and longitudinal factors associated with smoking cessation and recidivism among participants in the Women's Interagency HIV Study.From 1994 through 2011, a total of 2,961 HIV-infected and 981 HIV-uninfected women were enrolled and underwent semi-annual interviews and specimen collection. Smoking prevalence was evaluated annually and risk factors associated with time to smoking cessation and recidivism were analyzed in 2013 using survival models.The annual cigarette smoking prevalence declined from 57% in 1995 to 39% in 2011 (p-trend0.0001). Among smokers, factors significantly associated with a longer time to smoking cessation included less education, alcohol use, having health insurance,10-year smoking duration, self-reported poor health rating, and having hypertension. Pregnancy in the past 6 months was associated with a shorter time to cessation. Among HIV-infected women, additional risk factors for longer time to cessation included lower household income, use of crack/cocaine/heroin, CD4 cell count ≤200, and highly active antiretroviral therapy (HAART) use. Predictors of smoking recidivism included marijuana use, enrollment in 1994-1996, and not living in one's own place. Among HIV-infected women, enrollment in 2001-2002 and crack/cocaine/heroin use were associated with a shorter time to recidivism, whereas older age and HAART use were associated with a longer time to recidivism.Despite declining rates of cigarette smoking, integrated interventions are needed to help women with and at risk for HIV infection to quit smoking and sustain cessation.

OBJECTIVE AIDS-related primary central nervous system lymphoma (AR-PCNSL) has a poor prognosis. Improved understanding of specific patient, infectious, diagnostic, and treatment-related factors that affect overall survival (OS) is required to improve outcomes. DESIGN Population-based registry linkage study. METHODS Adult cases from the San Francisco AIDS registry (1990-2000) were matched with the California Cancer Registry (1985-2002) to ascertain AR-PCNSL data. Survival time was assessed through 31 December 2007. Risk factors and temporal trends for death were measured using two-sided Kaplan-Meier and Cox analyses. RESULTS Two hundred and seven AR-PCNSL patients were identified: 68% were white, 20% Hispanic, 10% African-American, and 2% Asian. Nineteen percent of patients had central nervous system (CNS) opportunistic infections diagnosed prior to AR-PCNSL. Fifty-seven percent of patients received radiation and/or chemotherapy and 12% used HAART prior to or within 30 days of AR-PCNSL diagnosis. One hundred and ninety-nine patients died (34 deaths/100 person-years). In adjusted analysis, prior CNS opportunistic infection diagnosis increased risk of death (hazard ratio 1.9, P = 0.0006) whereas radiation and/or chemotherapy decreased risk (hazard ratio 0.6, P

Cardiovascular disease (CVD) is increasingly common among women with HIV, but literature on nonlipid CVD risk factor management is lacking. We examined semiannual trends from 2006 to 2014 in hypertension treatment and control (blood pressure

Background: There is increasing evidence that chronic immune activation predisposes to non-Hodgkin lymphoma (NHL). Whether this association exists among women representative of the current HIV epidemic in the United States who are at high risk of HIV-associated NHL (AIDS-NHL), remains to be determined. Methods: We conducted a nested case–control study within the Women's Interagency HIV Study with longitudinally collected risk factor data and sera. Cases were HIV-infected women with stored sera collected at three time-windows 3 to 5 years, 1 to 3 years, and 0 to 1 year before AIDS-NHL diagnosis (n = 22). Three to six HIV-infected controls, without AIDS-NHL, were matched to each case on age, race, CD4+ T-cell count, and study follow-up time (n = 78). ORs and 95% confidence intervals (CI) for the association between one unit increase in log-transformed biomarker levels and AIDS-NHL were computed using random effect multivariate logistic regression models. Results: Elevated levels of sCD27 (OR = 7.21; 95% CI, 2.62–19.88), sCD30 (OR = 2.64; 95% CI, 1.24–5.64), and CXCL13 (OR = 2.56; 95% CI, 1.32–4.96) were associated with subsequent diagnosis of AIDS-NHL overall. Elevated sCD23 was associated with a two to three-fold increased risk of AIDS-NHL in certain subgroups, whereas elevated interleukin 6 was associated with a two-fold increased risk in the 0 to 1 year time-window, only. Conclusions: These findings support the hypothesis that chronic B-cell activation contributes to the development of AIDS-NHL in women. Impact: Soluble CD23 (sCD23), sCD27, sCD30, and CXCL13 may serve as biomarkers for AIDS-NHL. Cancer Epidemiol Biomarkers Prev; 22(11); 2084–93. ©2013 AACR.

By comparing younger to older participants enrolled in a HIV vaccine efficacy trial, we aimed to gain insights into the inclusion of adolescents in future trials. This was a sub-analysis of a multisite HIV vaccine randomized clinical trial in South Africa, conducted January–September 2007. Motivations for trial enrolment, social harms, adverse events and loss to follow-up were compared between younger (18–20 years old) and older participants (21–35 years old). Both younger (n = 238) and older participants (n = 563) were equally likely to report enrolling for altruistic reasons. Younger females were less likely than older participants to join for trial reimbursement (p = 0.005), while younger males were more likely to enrol because the vaccine may provide protection from HIV-acquisition (p

Objective HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic HPV infection – the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women.

OBJECTIVES To perform geriatric assessments in older HIV-infected adults in San Francisco and examine the association with age and the Veterans Aging Cohort Study (VACS) index scores. METHODS A cross-sectional study was conducted from 2012 to 2014 among HIV-infected patients ≥50 years at 2 San Francisco-based HIV clinics. We evaluated 4 health domains: (1) physical health and function (activities of daily living), instrumental activities of daily living (IADL), falls, gait speed, (2) social support (physical and perceived support, loneliness), (3) mental health (depression, anxiety, posttraumatic stress disorder) and cognition, and (4) behavioral and general health (antiretroviral adherence and quality of life). Contingency table and rank-sum analyses examined associations between these domains with age and VACS index scores. RESULTS Three hundred fifty-nine patients completed assessments (median age 57; 85% male; 57% white; 72% >high school education). On functional assessment, 39% reported dependence with ≥1 IADL, and 40% reported falls in the previous year. Fifty-eight percent experienced loneliness, 60% the lowest levels of perceived social support, 55% depression, and 12% posttraumatic stress disorder. Forty percent had possible mild cognitive impairment. Thirty percent reported poor or fair quality of life. Older age was associated with lower CD4 counts, balance problems, slower gait, lower anxiety, poorer general health, and higher antiretroviral adherence. VACS Index score was associated with dependence in ≥1 IADL and antiretroviral adherence. CONCLUSION In a large sample of older HIV-infected adults, multiple significant aging-related conditions were identified. Integrating geriatric assessment tools into HIV/AIDS clinical care may help target interventions to optimize clinical care and quality of life for older HIV-infected individuals.

Background: It is unclear whether immunosuppression leads to younger ages at cancer diagnosis among people living with human immunodeficiency virus (PLWH). A previous study found that most cancers are not diagnosed at a younger age in people with AIDS, with the exception of anal and lung cancers. This study extends prior work to include all PLWH and examines associations between AIDS, CD4 count, and age at cancer diagnosis. Methods: We compared the median age at cancer diagnosis between PLWH in the North American AIDS Cohort Collaboration on Research and Design and the general population using data from the Surveillance, Epidemiology and End Results Program. We used statistical weights to adjust for population differences. We also compared median age at cancer diagnosis by AIDS status and CD4 count. Results: After adjusting for population differences, younger ages at diagnosis (P < .05) were observed for PLWH compared with the general population for lung (difference in medians = 4 years), anal (difference = 4), oral cavity/pharynx (difference = 2), and kidney cancers (difference = 2) and myeloma (difference = 4). Among PLWH, having an AIDS-defining event was associated with a younger age at myeloma diagnosis (difference = 4; P = .01), and CD4 count

BackgroundCancer is increasingly common among persons with HIV.ObjectiveTo examine calendar trends in cumulative cancer incidence and hazard rate by HIV status.DesignCohort study.SettingNorth American AIDS Cohort Collaboration on Research and Design during 1996 to 2009.Participants86 620 persons with HIV and 196 987 uninfected adults.MeasurementsCancer type-specific cumulative incidence by age 75 years and calendar trends in cumulative incidence and hazard rates, each by HIV status.ResultsCumulative incidences of cancer by age 75 years for persons with and without HIV, respectively, were as follows: Kaposi sarcoma, 4.4% and 0.01%; non-Hodgkin lymphoma, 4.5% and 0.7%; lung cancer, 3.4% and 2.8%; anal cancer, 1.5% and 0.05%; colorectal cancer, 1.0% and 1.5%; liver cancer, 1.1% and 0.4%; Hodgkin lymphoma, 0.9% and 0.09%; melanoma, 0.5% and 0.6%; and oral cavity/pharyngeal cancer, 0.8% and 0.8%. Among persons with HIV, calendar trends in cumulative incidence and hazard rate decreased for Kaposi sarcoma and non-Hodgkin lymphoma. For anal, colorectal, and liver cancer, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (-9% per year), allowing greater opportunity to be diagnosed. Despite decreasing hazard rate trends for lung cancer, Hodgkin lymphoma, and melanoma, cumulative incidence trends were not seen because of the compensating effect of the declining mortality rate.LimitationSecular trends in screening, smoking, and viral co-infections were not evaluated.ConclusionCumulative cancer incidence by age 75 years, approximating lifetime risk in persons with HIV, may have clinical utility in this population. The high cumulative incidences by age 75 years for Kaposi sarcoma, non-Hodgkin lymphoma, and lung cancer support early and sustained antiretroviral therapy and smoking cessation.

Objectives: To assess the impact of HAART use on AIDS-defining Kaposi’s sarcoma and non-Hodgkin lymphoma (NHL) among adults with AIDS. Design: Registry linkage study. Methods: Adults diagnosed with AIDS from 1990 to 2000 in the San Francisco AIDS case registry were matched with cancer cases diagnosed from 1985 to 2002 in the California Cancer Registry. Multivariate Cox proportional hazard models were used to evaluate the risk and survival of AIDS-related Kaposi’s sarcoma, systemic NHL, and primary central nervous system (CNS) lymphoma. Results: Of the 14183 adults with AIDS, 3028 were diagnosed with Kaposi’s sarcoma, 776 with systemic NHL, and 254 with CNS NHL. After adjustment for potential confounders, more recent calendar period and use of HAART were significantly associated with a decreased risk of Kaposi’s sarcoma, whereas HAART use but not calendar period was significantly associated with systemic and CNS NHL. In adjusted analysis of Kaposi’s sarcoma survival time, there was strong evidence of a reduced risk of death associated with HAART use and more recent calendar period. In contrast, in adjusted analyses of systemic NHL survival time, HAART use was not associated with improved survival time; however, calendar period was associated with longer survival. In adjusted analysis of CNS NHL survival time, only cancer treatment was associated with a longer survival time. Conclusion: After controlling for calendar period and other confounders, use of HAART decreased the risk of Kaposi’s sarcoma, systemic NHL, and CNS NHL. Use of HAART also increased Kaposi’s sarcoma survival time but not NHL survival time. 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2011, 25:463‐471

Objective To estimate changes in high risk women’s knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination since introduction and marketing of HPV vaccines.

Purpose Prior reports of an increased risk of lung cancer in HIV-infected individuals have not always included control groups, nor considered other risk factors such as tobacco exposure. We sought to determine the role of HIV infection and highly active antiretroviral therapy (HAART) on lung cancer incidence in 2,651 HIV-infected and 898 HIV-uninfected women from the Women's Interagency HIV Study (WIHS). Methods A prospective study of the incidence rates of lung cancer was conducted, with cases identified through medical records, death certificates, and state cancer registries. Standardized incidence ratios (SIRs) were calculated to compare lung cancer incidence among HIV-infected and uninfected WIHS participants, with population-based expectations using the Surveillance, Epidemiology, and End Results registry. Behavioral characteristics in the WIHS were compared to US women by age and race adjusting the population-based data from the National Health and Nutritional Examination Survey (NHANES) III. Results Incidence rates of lung cancer were similar among HIV-infected and uninfected WIHS women. Lung cancer SIRs were increased in both HIV-infected and -uninfected women compared with population expectations, but did not differ by HIV status. Among HIV-infected women, lung cancer incidence rates were similar in pre-HAART and HAART eras. All WIHS women with lung cancer were smokers; the risk of lung cancer increased with cumulative tobacco exposure. WIHS women were statistically more likely to smoke than US women studied in NHANES III. Conclusion HIV infection is strongly associated with smoking behaviors that increase lung cancer risk. The role of HIV itself remains to be clarified.

Background:To assess trends in mortality and cause of death for women with HIV, we studied deaths over a 10-year period among participants in the Women's Interagency HIV Study, a representative US cohort.Methods:Deaths were ascertained by National Death Index Plus match, and causes of death determin

BACKGROUND: The objective of this study was to estimate the incidence of invasive cervical cancer (ICC) in women with human immunodeficiency virus (HIV) and compare it with the incidence in HIV-uninfected women. METHODS: In a cohort study of HIV-infected and uninfected women who had Papanicolaou tests obtained every 6 months, pathology reports were retrieved for women who had biopsy results or a self-report of ICC. Histology was reviewed when reports confirmed ICC. Incidence rates were calculated and compared with those in HIV-negative women. RESULTS: After a median follow-up of 10.3 years, 3 ICCs were confirmed in HIV-seropositive women, and none were confirmed in HIV-seronegative women. The ICC incidence rate was not found to be associated significantly with HIV status (HIV-negative women [0 of 100,000 person-years] vs HIV-positive women [21.4 of 100,000 person-years]; P = .59). A calculated incidence rate ratio standardized to expected results from the Surveillance Epidemiology and End Results database that was restricted to HIV-infected Women's Interagency HIV Study participants was 1.32 (95% confidence interval, 0.27-3.85; P = 0.80). CONCLUSIONS: Among women with HIV in a prospective study that incorporated cervical cancer prevention measures, the incidence of ICC was not significantly higher than that in a comparison group of HIV-negative women. Cancer 2009. Published 2009 by the American Cancer Society.

To study anal intraepithelial neoplasia and its associations with anal and cervical human papillomavirus (HPV), cervical neoplasia, host immune status, and demographic and behavioral risk factors in women with and at risk for HIV infection.Point-prevalence analysis nested within a prospective study of women seen at three clinical centers of the Women's Interagency HIV Study.In 2001-2003 participants were interviewed, received a gynecological examination, anal and cervical cytology testing and, if abnormal, colposcopy-guided or anoscopy-guided biopsy of visible lesions. Exfoliated cervical and anal specimens were assessed for HPV using PCR and type-specific HPV probing. Logistic regression analyses were performed, and odds ratios (ORs) estimated risks for anal intraepithelial neoplasia.Four hundred and seventy HIV-infected and 185 HIV-uninfected women were enrolled. Low-grade anal intraepithelial neoplasia was present in 12% of HIV-infected and 5% of HIV-uninfected women. High-grade anal intraepithelial neoplasia was present in 9% of HIV-infected and 1% of HIV-uninfected women. In adjusted analyses among HIV-infected women, the risk factors for low-grade anal intraepithelial neoplasia were younger age [OR = 0.59, 95% confidence interval (CI) = 0.36-0.97], history of receptive anal intercourse (OR = 3.2, 95% CI = 1.5-6.8), anal HPV (oncogenic types only OR = 11, 95% CI = 1.2-103; oncogenic and nononcogenic types OR = 11, 95% CI = 1.3-96), and cervical HPV (oncogenic and nononcogenic types OR = 3.5, 95% CI = 1.1-11). In multivariable analyses among HIV-infected women, the only significant risk factor for high-grade anal intraepithelial neoplasia was anal HPV infection (oncogenic and nononcogenic types OR = 7.6, 95% CI = 1.5-38).Even in the era of highly active antiviral therapy, the prevalence of anal intraepithelial neoplasia was 16% in HIV-infected women. After controlling for potential confounders, several risk factors for low-grade anal intraepithelial neoplasia differed from risk factors for high-grade anal intraepithelial neoplasia.

To assess risk factors for macrosomic infant birth among Latina women. Prospective study of Latina women recruited during pregnancy from prenatal clinic at San Francisco General Hospital. Information was obtained through a structured interview and review of medical records. A total of 11% of women delivered macrosomic infants (birth weight >4000 g). In unadjusted analyses, significant risk factors for macrosomia included older maternal age, increasing gravidity, previous history of macrosomic birth and pre-pregnancy overweight. After adjusting for confounders using multivariate analyses, older mothers (10-year increments) had an elevated risk of macrosomia (odds ratio (OR) 2.59; 95% confidence interval (CI) 1.28 to 5.24). Efforts to reduce macrosomia in Latina women should focus on older mothers.

Background: The effects of HIV infection, highly active antiretroviral therapy (HAART), and specific antiretroviral agents on lipoproteins in women are not well described. Methods: In a cross-sectional substudy of the Women's Interagency HIV Study with 623 HIV-negative and 1556 HIV-positive women (636 untreated, 419 on non-protease inhibitor [PI] HAART, and 501 on PI-containing HAART), we performed multivariate analyses of associations among fasting lipoprotein levels, HIV infection, and HAART. Results: Untreated HIV-positive women had lower high-density lipoprotein cholesterol (HDL-C) and higher triglycerides (TGs) but not lower low-density lipoprotein cholesterol (LDL-C) than HIV-negative women and were the most likely to have unfavorable HDL-C by National Cholesterol Education Program (NCEP) guidelines. PI HAART users had higher LDL-C than untreated HIV-infected women (107 vs. 100 mg/dL, P = 0.0006) and were the most likely to have unfavorable LDL-C and TGs by NCEP guidelines. HIV-negative women and non-PI HAART users had similar HDL-C levels (55 and 53 mg/dL, respectively), which were higher than those in untreated HIV-infected women and PI HAART users (42 and 49 mg/dL, respectively; P < 0.001 for all). Lamivudine, didanosine, nevirapine, and efavirenz were independently associated with higher HDL-C (P < 0.001 for all). Ritonavir, indinavir/ritonavir, and nelfinavir were associated with higher LDL-C (P < 0.01 for all). Stavudine, abacavir, and all ritonavir-containing regimens were associated with higher TGs (P < 0.05 for all), and tenofovir was associated with lower TGs (P = 0.009). Conclusions: A dyslipidemic pattern was associated with HIV infection itself, was more severe in users of PI-containing HAART, but was not present in women taking non-PI HAART.

Suboptimal adherence to antiretroviral (ARV) therapy among HIV-infected individuals is associated with increased risk of progression to AIDS and the development of HIV resistance to ARV medications. To examine whether the luteal phase of the menstrual cycle is independently associated with suboptimal adherence to single tablet regimen (STR) ARV medication, data were analyzed from a multicenter cohort study of HIV-infected women who reported regular menstrual cycles and were taking an STR. In a cross-sectional analysis, suboptimal adherence to an STR among women in their follicular phase was compared with suboptimal adherence among women in their luteal phase. In two-way crossover analyses, whereby the same woman was assessed for STR medication adherence in both her follicular and luteal phases, the estimated exact conditional odds of non-adherence to an STR was measured. In adjusted logistic regression analysis of the cross-sectional data (N=327), women with ≤12 years of education were more than three times more likely to have suboptimal adherence (OR=3.6, p=.04) compared to those with >12 years of education. Additionally, women with Center for Epidemiological Studies Depression Scale (CES-D) scores ≥23 were 2.5-times more likely to have suboptimal adherence (OR=2.6, p=.02) compared to those with CES-D scores

ObjectivesTo determine the lung cancer incidence and survival time among HIV-infected and uninfected women and men.DesignTwo longitudinal studies of HIV infection in the United States.MethodsData from 2549 women in the Women's Interagency HIV Study (WIHS) and 4274 men in the Multicenter AIDS Cohort Study (MACS), all with a history of cigarette smoking, were analyzed. Lung cancer incidence rates and incidence rate ratios were calculated using Poisson regression analyses. Survival time was assessed using Kaplan-Meier and Cox proportional-hazard analyses.ResultsThirty-seven women and 23 men developed lung cancer (46 HIV-infected and 14 HIV-uninfected) during study follow-up. In multivariable analyses, the factors that were found to be independently associated with a higher lung cancer incidence rate ratios were older age, less education, 10 or more pack-years of smoking, and a prior diagnosis of AIDS pneumonia (vs. HIV-uninfected women). In an adjusted Cox model that allowed different hazard functions for each cohort, a history of injection drug use was associated with shorter survival, and a lung cancer diagnosis after 2001 was associated with longer survival. In an adjusted Cox model restricted to HIV-infected participants, nadir CD4 lymphocyte cell count less than 200 was associated with shorter survival time.ConclusionsOur data suggest that pulmonary damage and inflammation associated with HIV infection may be causative for the increased risk of lung cancer. Encouraging and assisting younger HIV-infected smokers to quit and to sustain cessation of smoking is imperative to reduce the lung cancer burden in this population.

Purpose To describe changes in knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination among women at high risk for cervical cancer in the first five years after introduction of HPV vaccination. Methods In 2007, 2008–9, and 2011, women in a multicenter U.S. cohort study completed 44-item self-report questionnaires assessing knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results across time were assessed for individuals, and three study enrollment cohorts were compared. Knowledge scores were correlated with demographic variables, measures of education and attention, and medical factors. Associations were assessed in multivariable models. Results In all, 974 women completed three serial questionnaires; most were minority, low income, and current or former smokers. The group included 652 (67%) HIV infected and 322 (33%) uninfected. Summary knowledge scores (possible range 0–24) increased from 2007 (12.8, S.D. 5.8) to 2008–9 (13.9, S.D. 5.3, P, Highlights • Women at high risk for cervical cancer have substantial knowledge gaps about prevention. • Knowledge gaps improved after an intervention, but little additional improvement followed. • Poor and less educated women have lower knowledge scores despite higher cancer risk.

Author(s): Scott, Hyman M; Irvin, Risha; Wilton, Leo; Van Tieu, Hong; Watson, Chauncey; Magnus, Manya; Chen, Iris; Gaydos, Charlotte; Hussen, Sophia A; Mannheimer, Sharon; Mayer, Kenneth; Hessol, Nancy A; Buchbinder, Susan | Abstract: BackgroundBlack men who have sex with men (MSM) have a high prevalence of bacterial sexually transmitted infections (STIs), and individual risk behavior does not fully explain the higher prevalence when compared with other MSM. Using the social-ecological framework, we evaluated individual, social and sexual network, and structural factors and their association with prevalent STIs among Black MSM.MethodsThe HIV Prevention Trials Network 061 was a multi-site cohort study designed to determine the feasibility and acceptability of a multi-component intervention for Black MSM in six US cities. Baseline assessments included demographics, risk behavior, and social and sexual network questions collected information about the size, nature and connectedness of their sexual network. Logistic regression was used to estimate the odds of having any prevalent sexually transmitted infection (gonorrhea, chlamydia, or syphilis).ResultsA total of 1,553 Black MSM were enrolled in this study. In multivariate analysis, older age (aOR = 0.57; 95% CI 0.49-0.66, pl0.001) was associated with a lower odds of having a prevalent STI. Compared with reporting one male sexual partner, having 2-3 partners (aOR = 1.74; 95% CI 1.08-2.81, pl0.024) or more than 4 partners (aOR = 2.29; 95% CI 1.43-3.66, pl0.001) was associated with prevalent STIs. Having both Black and non-Black sexual partners (aOR = 0.67; 95% CI 0.45-0.99, p = 0.042) was the only sexual network factor associated with prevalent STIs.ConclusionsAge and the number and racial composition of sexual partners were associated with prevalent STIs among Black MSM, while other sexual network factors were not. Further studies are needed to evaluate the effects of the individual, network, and structural factors on prevalent STIs among Black MSM to inform combination interventions to reduce STIs among these men.

BACKGROUND Determining cervical precancer risk among human immunodeficiency virus (HIV)-infected women who despite a normal Pap test are positive for oncogenic human papillomavirus (oncHPV) types is important for setting screening practices. METHODS A total of 2791 HIV-infected and 975 HIV-uninfected women in the Women's Interagency HIV Study were followed semiannually with Pap tests and colposcopy. Cumulative risks of cervical intraepithelial neoplasia grade 2 or greater (CIN-2+; threshold used for CIN treatment) and grade 3 or greater (CIN-3+; threshold to set screening practices) were measured in HIV-infected and HIV-uninfected women with normal Pap tests, stratified by baseline HPV results, and also in HIV-infected women with a low-grade squamous intraepithelial lesion (LSIL; benchmark indication for colposcopy). RESULTS At baseline, 1021 HIV-infected and 518 HIV-uninfected women had normal Pap tests, of whom 154 (15%) and 27 (5%), respectively, tested oncHPV positive. The 5-year CIN-2+ cumulative risk in the HIV-infected oncHPV-positive women was 22% (95% confidence interval [CI], 9%-34%), 12% (95% CI, 0%-22%), and 14% (95% CI, 2%-25%) among those with CD4 counts

Objective: To determine the prevalence of infection with herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) among women with and at high risk for HIV infection, and to evaluate the effect of HAART on the recurrence of genital lesions. Methods: We evaluated the epidemiology and clinical manifestations associated with HSV-1 and HSV-2 among 1796 HIV-infected and 476 HIV-uninfected women enrolled in a multisite cohort study. Serum antibodies to HSV-1 and HSV-2 at baseline and self-reported history of genital herpes, reports of recent genital sores and presence of genital ulcers on examination, and use of HAART regimen at each study visit were analyzed. Results: Reactivity to HSV-1 only and HSV-2 only was detected in 18% and 20% of HIV-infected, and in 28% and 18% of HIV-uninfected participants respectively; 58% of HIV-infected women and 45% of HIV-uninfected women were seropositive for both HSV types. Reactivity to HSV-2 was associated with increasing age, more male sexual partners, earlier sexual debut, African-American race, Latina ethnicity, less education and lower income. HIV-uninfected women reported significantly fewer genital sores than HIV-infected women who had used HAART for at least 1 year and had optimal CD4 cell gain and viral suppression (adjusted odds ratio (OR), 0.19; 95% confidence interval (Cl), 0.13-0.28). Conclusion: Use of HAART and subsequent immune recovery does not completely eliminate the effect of HIV infection on genital lesions among women with concurrent HSV-2 infection.

Pre-exposure prophylaxis (PrEP) is a promising HIV prevention approach for men who have sex with men (MSM), however non-adherence could limit its effectiveness. Understanding the experiences of HIV-uninfected MSM taking routine medications can provide valuable insights into open label PrEP adherence in real world settings and guide development of PrEP adherence interventions. In this study, we examined self-reported medication-taking experiences and facilitators and barriers of medication adherence among a geographically-diverse online sample of HIV-uninfected US MSM. Among 1480 participants, 806 (54%) reported taking medications regularly, of whom 80% reported taking medications for treatment and 55% for prevention purposes. Facilitators of medication adherence included establishing a routine, keeping medication visible, and using a pill-box; barriers included forgetting, changes in routine, and being busy or away from home. Only 45% rated their medication-taking ability as excellent, and 36% reported not missing any doses in the past 30 days. In multivariable analyses, older men and those not reporting any adherence barriers were more likely to report excellent adherence, and men willing to use PrEP were more likely to report perfect 30-day adherence. Counseling strategies to build pill-taking routines and support younger MSM are suggested to maximize the public health impact of PrEP.