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.

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.

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.

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.

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.

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.

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.

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.

Trends in the San Francisco Human Immunodeficiency Virus Epidemic in the "Getting to Zero" Era.

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.

Loneliness in Older Adults Living with HIV.

We conducted a cross-sectional study among HIV-positive adults age ≥ 50 in San Francisco to evaluate the frequency of loneliness, characteristics of those who reported loneliness, and the association of loneliness with functional impairment and health-related quality of life (HRQoL). Participants (N = 356) were predominately male (85%); 57% were white; median age was 56. 58% reported any loneliness symptoms with 24% reporting mild, 22% moderate and 12% severe loneliness. Lonely participants were more likely to report depression, alcohol and tobacco use, and have fewer relationships. In unadjusted models, loneliness was associated with functional impairment and poor HRQoL. In adjusted models, low income and depression remained associated with poor HRQoL, while low income, higher VACS index and depression were associated with functional impairment. A comprehensive care approach, incorporating mental health and psychosocial assessments with more traditional clinical assessments, will be needed to improve health outcomes for the aging HIV-positive population.

RESUMEN: Realizamos un estudio transversal en adultos mayores de 50 años con VIH en San Francisco para evaluar la frecuencia de la soledad, características de aquellos que reportan soledad, y la asociación de la soledad con el deterioro funcional y la calidad de vida relacionada con la salud (HRQoL). Los participantes (N = 356) fueron principalmente hombres (85%); 57% de raza blanca, la mediana de edad fue 56 años. El 58% reportó cualquier síntoma de soledad con un 24% reportando soledad leve, 22% soledad moderada, y 12% soledad severa. En los participantes que refirieron soledad era más probable que reportaran depresión, consumo de tabaco o alcohol, y menos relaciones sociales. En modelos sin ajustar, la soledad estaba asociada con deterioro funcional y baja calidad de vida relacionada con la salud. En modelos ajustados, tener bajos ingresos y depresión continuaron teniendo asociación con una baja calidad de vida relacionada con la salud, mientras que tener bajos ingresos, un índice más alto de VACS y depresión estaban asociados con deterioro funcional. Un sistema de cuidado integral, incorporando la salud mental y valoraciones psicológicas y sociales con evaluaciones médicas tradicionales, serán necesarios para poder mejorar los índices de salud de las personas VIH positivas que envejecen.

Prevalence, Comorbidity, and Correlates of Psychiatric and Substance Use Disorders and Associations with HIV Risk Behaviors in a Multisite Cohort of Women Living with HIV.

We used the World Health Organization's Composite International Diagnostic Interview to determine the prevalence, comorbidity, and correlates of lifetime and 12-month behavioral health disorders in a multisite cohort of 1027 women living with HIV in the United States. Most (82.6%) had one or more lifetime disorders including 34.2% with mood disorders, 61.6% with anxiety disorders, and 58.3% with substance use disorders. Over half (53.9%) had at least one 12-month disorder, including 22.1% with mood disorders, 45.4% with anxiety disorders, and 11.1% with substance use disorders. Behavioral health disorder onset preceded HIV diagnosis by an average of 19 years. In multivariable models, likelihood of disorders was associated with women's race/ethnicity, employment status, and income. Women with 12-month behavioral health disorders were significantly more likely than their counterparts to engage in subsequent sexual and substance use HIV risk behaviors. We discuss the complex physical and behavioral health needs of women living with HIV.

HIV Infection, Immunosuppression, and Age at Diagnosis of Non-AIDS-Defining Cancers.

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 <200 cells/µL (vs ≥500) was associated with a younger age at lung cancer diagnosis (difference = 4; P = .006). Conclusions: Among PLWH, most cancers are not diagnosed at younger ages. However, this study strengthens evidence that lung cancer, anal cancer, and myeloma are diagnosed at modestly younger ages, and also shows younger ages at diagnosis of oral cavity/pharynx and kidney cancers, possibly reflecting accelerated cancer progression, etiologic heterogeneity, or risk factor exposure in PLWH.

Cervical cancer incidence after up to 20 years of observation among women with HIV.

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.

Food Insecurity and Aging Outcomes in Older Adults Living with HIV.

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.

Menstrual cycle phase and single tablet antiretroviral medication adherence in women with HIV.

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 <23. In conditional logistic regression analyses of the crossover data (N=184), having childcare responsibilities was associated with greater odds of ≤95% adherence. Menstrual cycle phase was not associated with STR adherence in either the cross-sectional or crossover analyses. The lack of association between phase of the menstrual cycle and adherence to an STR in HIV-infected women means attention can be given to other more important risk factors for suboptimal adherence, such as depression, level of education, and childcare responsibilities.

Cumulative Incidence of Cancer Among Persons With HIV in North America: A Cohort Study.

BACKGROUND: Cancer is increasingly common among persons with HIV. OBJECTIVE: To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status. DESIGN: Cohort study. SETTING: North American AIDS Cohort Collaboration on Research and Design during 1996 to 2009. PARTICIPANTS: 86 620 persons with HIV and 196 987 uninfected adults. MEASUREMENTS: Cancer type-specific cumulative incidence by age 75 years and calendar trends in cumulative incidence and hazard rates, each by HIV status. RESULTS: Cumulative 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. LIMITATION: Secular trends in screening, smoking, and viral co-infections were not evaluated. CONCLUSION: Cumulative 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.

Cervical Precancer Risk in HIV-Infected Women Who Test Positive for Oncogenic Human Papillomavirus Despite a Normal Pap Test.

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 <350, 350-499, and ≥500 cells/µL, respectively, whereas it was 10% (95% CI, 0%-21%) in those without HIV. For CIN-3+, the cumulative risk averaged 4% (95% CI, 1%-8%) in HIV-infected oncHPV-positive women, and 10% (95% CI, 0%-23%) among those positive for HPV type 16. In HIV-infected women with LSIL, CIN-3+ risk was 7% (95% CI, 3%-11%). In multivariate analysis, HIV-infected HPV16-positive women had 13-fold (P = .001) greater CIN-3+ risk than oncHPV-negative women (referent), and HIV-infected women with LSIL had 9-fold (P < .0001) greater risk. CONCLUSIONS: HIV-infected women with a normal Pap result who test HPV16 positive have high precancer risk (similar to those with LSIL), possibly warranting immediate colposcopy. Repeat screening in 1 year may be appropriate if non-16 oncHPV is detected.

Trends and disparities in antiretroviral therapy initiation and virologic suppression among newly treatment-eligible HIV-infected individuals in North America, 2001-2009.

BACKGROUND: Since the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes. METHODS: We analyzed data on HIV-infected individuals newly clinically eligible for ART (ie, first reported CD4+ count<350 cells/µL or AIDS-defining illness, based on treatment guidelines during the study period) from 17 North American AIDS Cohort Collaboration on Research and Design cohorts. Outcomes included timely ART initiation (within 6 months of eligibility) and virologic suppression (≤500 copies/mL, within 1 year). We examined time trends and considered differences by geographic location, age, sex, transmission risk, race/ethnicity, CD4+ count, and viral load, and documented psychosocial barriers to ART initiation, including non-injection drug abuse, alcohol abuse, and mental illness. RESULTS: Among 10,692 HIV-infected individuals, the cumulative incidence of 6-month ART initiation increased from 51% in 2001 to 72% in 2009 (Ptrend<.001). The cumulative incidence of 1-year virologic suppression increased from 55% to 81%, and among ART initiators, from 84% to 93% (both Ptrend<.001). A greater number of psychosocial barriers were associated with decreased ART initiation, but not virologic suppression once ART was initiated. We found significant heterogeneity by state or province of residence (P<.001). CONCLUSIONS: In the last decade, timely ART initiation and virologic suppression have greatly improved in North America concurrent with the development of better-tolerated and more potent regimens, but significant barriers to treatment uptake remain, both at the individual level and systemwide.

Alcohol consumption trajectory patterns in adult women with HIV infection.

HIV-infected women with excessive alcohol consumption are at risk for adverse health outcomes, but little is known about their long-term drinking trajectories. This analysis included longitudinal data, obtained from 1996 to 2006, from 2,791 women with HIV from the Women's Interagency HIV Study. Among these women, the proportion in each of five distinct drinking trajectories was: continued heavy drinking (3 %), reduction from heavy to non-heavy drinking (4 %), increase from non-heavy to heavy drinking (8 %), continued non-heavy drinking (36 %), and continued non-drinking (49 %). Depressive symptoms, other substance use (crack/cocaine, marijuana, and tobacco), co-infection with hepatitis C virus (HCV), and heavy drinking prior to enrollment were associated with trajectories involving future heavy drinking. In conclusion, many women with HIV change their drinking patterns over time. Clinicians and those providing alcohol-related interventions might target those with depression, current use of tobacco or illicit drugs, HCV infection, or a previous history of drinking problems.