Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies.

BACKGROUND: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. METHODS: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. RESULTS: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. CONCLUSIONS: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

Age-Specific Prevalence of Anal and Cervical Human Papillomavirus Infection and High-Grade Lesions in 11 177 Women by Human Immunodeficiency Virus Status: A Collaborative Pooled Analysis of 26 Studies.

BACKGROUND: Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention. METHODS: We centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology. RESULTS: In HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+. CONCLUSIONS: Age-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

Development of a curriculum integrating biostatistics and study design with core sciences in an organ system block.

INTRODUCTION: The objectives of this study were to develop and evaluate a curriculum that integrated biostatistics and research design content with core sciences content within a pharmacy course. METHODS: An inquiry curriculum was developed in 2019 and included lectures on biostatistics and research design with small group discussions of clinical research papers directly related to the core sciences content. Students' perceptions and pass rates between students who did (2019 cohort) and did not (2018 cohort) undergo the curriculum were compared. Test scores taken approximately one year after completion of each cohort's course were also compared. RESULTS: Of 127 students in the 2019 cohort, 120 (94%) responded. Over 90% agreed or strongly agreed that inquiry and core sciences contents were integrated well. The 2019 cohort had a significantly higher pass rate than the 2018 cohort on two of three assessment questions evaluated: one multiple choice question (P = .037) and one short answer question (P = .013). After adjustments for baseline characteristics, retention study volunteers from the 2019 cohort had a significantly higher percent test score than those from the 2018 cohort (parameter estimate = 8.48%; P = .026). CONCLUSIONS: An inquiry curriculum consisting of select biostatistics and research design topics can be integrated with a core sciences curriculum in a large integrated pharmacy course. Inclusion of this content increased student academic performance and retention of knowledge and skills.

Effect of Social Determinants of Health on Uncontrolled Human Immunodeficiency Virus (HIV) Infection Among Persons With HIV in San Francisco, California.

Background: In 2010-2014, the San Francisco Department of Public Health (SFDPH) established programs to rapidly link people with human immunodeficiency virus (PWH) to care and offer antiretroviral therapy (ART) at human immunodeficiency virus (HIV) diagnosis. Such programs reduced the number of PWH out of care or with detectable HIV viral load (ie, uncontrolled HIV infection). We investigated the role of social determinants of health (SDH) on uncontrolled HIV. Methods: Cross-sectional data from adult PWH diagnosed and reported to the SFDPH as of December 31, 2019, prescribed ART, and with confirmed San Francisco residency during 2017-2019 were analyzed in conjunction with SDH metrics derived from the American Community Survey 2015-2019. We focused on 5 census tract-level SDH metrics: percentage of residents below the federal poverty level, with less than a high school diploma, or uninsured; median household income; and Gini index. We compared uncontrolled HIV prevalence odds ratios (PORs) across quartiles of each metric independently using logistic regression models. Results: The analysis included 7486 PWH (6889 controlled HIV; 597 uncontrolled HIV). Unadjusted PORs of uncontrolled HIV rose with increasingly marginalized quartiles, compared to the least marginalized quartile for each metric. Adjusting for demographics and transmission category, the POR for uncontrolled HIV for PWH in the most marginalized quartile remained significant across metrics for poverty (POR = 2.0; confidence interval [CI] = 1.5-2.6), education (POR = 2.4; CI = 1.8-3.2), insurance (POR = 1.8; CI = 1.3-2.5), income (POR = 1.8; CI = 1.4-2.3), and income inequality (POR = 1.5; CI = 1.1-2.0). Conclusions: Beyond demographics, SDH differentially affected the ability of PWH to control HIV. Despite established care programs, PWH experiencing socioeconomic marginalization require additional support to achieve health outcome goals.

Disparities in Integrase Inhibitor Usage in the Modern HIV Treatment Era: A Population-Based Study in a US City.

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.

Sensitivity and Specificity of the National Death Index for Multiple Causes of Death in People With HIV.

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.

Timing of Antiretroviral Therapy Initiation and Risk of Cancer Among Persons Living With Human Immunodeficiency Virus.

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.

Risk of smoking-related cancers among women and men living with and without HIV.

OBJECTIVES: We 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. DESIGN: Data 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. METHODS: Incidence rates, relative risks, and adjusted population attributable fractions (PAFs) were calculated for smoking-related cancers. RESULTS: During 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 < 0.01) and higher for people living with HIV (PLWH, 348/100 000) than for those without HIV (162/100 000; P < 0.01). Unadjusted incidence rates in PLWH were higher than in those without HIV when stratifying by cumulative pack-years of smoking (all P values <0.01). In adjusted interaction models, the effects of cumulative pack-years of smoking were significantly stronger in women. The adjusted PAFs for smoking-related cancers were nonsignificantly higher in the women than in the men (39 vs. 28%; P = 0.35). CONCLUSION: HIV looks to be an independent risk factor for smoking-related cancers and women appear to have a greater risk than men. These results highlight the need for interventions to help PLWH, especially women, quit smoking and sustain cessation to reduce their risk of smoking-related cancers.

Decreased Time From Human Immunodeficiency Virus Diagnosis to Care, Antiretroviral Therapy Initiation, and Virologic Suppression during the Citywide RAPID Initiative in San Francisco.

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 < .0001) and from first care visit to ART initiation decreased from 28 to 1 (96%; P < .0001). By 2017, 28% of new diagnoses had a rapid start, which was independently associated with Latinx ethnicity (AOR, 1.73; 95% CI, 1.15-2.60) and recent year of diagnosis (2017; AOR, 16.84; 95% CI, 8.03-35.33). Persons with a rapid ART start were more likely to be virologically suppressed within 12 months of diagnosis than those with a non-rapid start (RR, 1.17; 95% CI, 1.10-1.24). 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.

Primary HPV and Molecular Cervical Cancer Screening in US Women Living With Human Immunodeficiency Virus.

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.

Beyond Overdose: Drug-Related Deaths in People With and Without HIV in San Francisco, 2007-2018.

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.

Epidemiological evidence that common HPV types may be common because of their ability to evade immune surveillance: Results from the Women's Interagency HIV study.

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 (PHIV+ = a*PHIV- + b*PHIV- 2 ; R2 = 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.

Functional deficits and other psychiatric associations with abnormal scores on the Montreal Cognitive Assessment (MoCA) in older HIV-infected patients.

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 older. MEASUREMENTS: Unadjusted 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. RESULTS: Thirty-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.

Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia With Anal Cancer Risk in Persons Living With HIV in the United States and Canada.

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 <50 vs ≥500 cells/µL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/µL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6). 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.

A longitudinal study assessing differences in causes of death among housed and homeless people diagnosed with HIV in San Francisco.

BACKGROUND: San Francisco has implemented several programs addressing the needs of two large vulnerable populations: people living with HIV and those who are homeless. Assessment of these programs on health outcomes is paramount for reducing preventable deaths. METHODS: Individuals diagnosed with HIV/AIDS and reported to the San Francisco Department of Public Health HIV surveillance registry, ages 13 years or older, who resided in San Francisco at the time of diagnosis, and who died between January 1, 2002, and December 31, 2016 were included in this longitudinal study. The primary independent variable was housing status, dichotomized as ever homeless since diagnosed with HIV, and the dependent variables were disease-specific causes of death, as noted on the death certificate. The Cochran-Armitage test measured changes in the mortality rates over time and unadjusted and adjusted Poisson regression models measured prevalence ratios (PR) and 95% confidence intervals (CI) for causes of death. RESULTS: A total of 4158 deceased individuals were included in the analyses: the majority were male (87%), ages 40-59 years old at the time of death (64%), non-Hispanic White (60%), men who have sex with men (54%), had an AIDS diagnosis prior to death (87%), and San Francisco residents at the time of death (63%). Compared to those who were housed, those who were homeless were more likely to be younger at time of death, African American, have a history of injecting drugs, female or transgender, and were living below the poverty level (all p values < 0.0001). Among decedents who were SF residents at the time of death, there were declines in the proportion of deaths due to AIDS-defining conditions (p < 0.05) and increases in accidents, cardiomyopathy, heart disease, ischemic disease, non-AIDS cancers, and drug overdoses (p < 0.05). After adjustment, deaths due to mental disorders (aPR = 1.63, 95% CI 1.24, 2.14) were more likely and deaths due to non-AIDS cancers (aPR = 0.63, 95% CI 0.44, 0.89) were less likely among those experiencing homelessness. CONCLUSIONS: Additional efforts are needed to improve mental health services to homeless people with HIV and prevent mental-health related mortality.

Homelessness at diagnosis is associated with death among people with HIV in a population-based study of a US city.

OBJECTIVE: San 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. DESIGN: Population-based incidence-density case-control study. METHODS: Among 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. RESULTS: Of 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). CONCLUSION: People 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.

HIV Seroconversion in the Era of Pharmacologic Prevention: A Case-Control Study at a San Francisco STD Clinic.

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.

Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis.

BACKGROUND: 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. METHODS: We did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL. FINDINGS: Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16·5, 95% CI 14·2-19·2, p<0·0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4·4, 3·7-5·3, p<0·0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% [101/228] for cervical cancer in HIV-negative women (PR vs normal cytology 14·1, 11·1-17·9, p<0·0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% [11/527] in cervical high-risk HPV-negative women up to 24% [33/138] in cervical HPV16-positive women; PR 12·9, 95% CI 6·7-24·8, p<0·0001) and HIV-positive women (from 8% [84/1094] to 17% [31/186]; 2·3, 1·6-3·4, p<0·0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% [5/498] in normal cytology up to 22% [59/273] in cervical HSIL; PR 23·1, 9·4-57·0, p<0·0001) and HIV-positive women (from 7% [105/1421] to 25% [25/101]; 3·6, 2·5-5·3, p<0·0001). Prevalence of HPV16-positive anal HSIL was 23-25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women). INTERPRETATION: HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women. FUNDING: International Agency for Research on Cancer.

Association of immunosuppression and HIV viraemia with non-Hodgkin lymphoma risk overall and by subtype in people living with HIV in Canada and the USA: a multicentre cohort study.

BACKGROUND: Research 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. METHODS: We 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. FINDINGS: Of 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; <50 cells per µL vs ≥500 cells per µL, hazard ratio [HR] 3·2, 95% CI 2·2-4·7) and average viral load during a 3-year window lagged by 6 months (a cumulative measure; ≥100 000 copies per mL vs ≤500 copies per mL, HR 9·6, 95% CI 6·5-14·0). These measures were also the key predictors of risk for diffuse large B-cell lymphoma (recent CD4 count <50 cells per µL vs ≥500 cells per µL, HR 2·4, 95% CI 1·4-4·2; average viral load ≥100 000 copies per mL vs ≤500 copies per mL, HR 7·5, 95% CI 4·5-12·7). However, recent CD4 count was the sole key predictor of risk for CNS non-Hodgkin lymphoma (<50 cells per µL vs ≥500 cells per µL, HR 426·3, 95% CI 58·1-3126·4), and proportion of time viral load was greater than 500 copies per mL during the 3-year window (a cumulative measure) was the sole key predictor for Burkitt lymphoma (100% vs 0%, HR 41·1, 95% CI 9·1-186·6). INTERPRETATION: Both recent immunosuppression and prolonged HIV viraemia have important independent roles in the development of non-Hodgkin lymphoma, with likely subtype heterogeneity. Early and sustained antiretroviral therapy to decrease HIV replication, dampen B-cell activation, and restore overall immune function is crucial for preventing non-Hodgkin lymphoma. FUNDING: National Institutes of Health, Centers for Disease Control and Prevention, US Agency for Healthcare Research and Quality, US Health Resources and Services Administration, Canadian Institutes of Health Research, Ontario Ministry of Health and Long Term Care, and the Government of Alberta.

Racial differences in human papilloma virus types amongst United States women with HIV and cervical precancer.

OBJECTIVE: Recent 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. DESIGN: Women 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). RESULTS: Among 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. CONCLUSION: HPV16 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.