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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., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes., Methods: We included participants receiving care in academic and community-based outpatient HIV clinical cohorts in the USA and Canada from Jan 1, 2000, to Dec 31, 2014, who contributed to the North American AIDS Cohort Collaboration on Research and Design and who had validated non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, or end-stage renal disease outcomes. Traditional risk factors were tobacco smoking, hypertension, elevated total cholesterol, type 2 diabetes, renal impairment (stage 4 chronic kidney disease), and hepatitis C virus and hepatitis B virus infections. HIV-related risk factors were low CD4 count (<200 cells per μL), detectable plasma HIV RNA (>400 copies per mL), and history of a clinical AIDS diagnosis. PAFs and 95% CIs were estimated to quantify the proportion of outcomes that could be avoided if the risk factor was prevented., Findings: In each of the study populations for the four outcomes (1405 of 61 500 had non-AIDS-defining cancer, 347 of 29 515 had myocardial infarctions, 387 of 35 044 had end-stage liver disease events, and 255 of 35 620 had end-stage renal disease events), about 17% were older than 50 years at study entry, about 50% were non-white, and about 80% were men. Preventing smoking would avoid 24% (95% CI 13-35) of these cancers and 37% (7-66) of the myocardial infarctions. Preventing elevated total cholesterol and hypertension would avoid the greatest proportion of myocardial infarctions: 44% (30-58) for cholesterol and 42% (28-56) for hypertension. For liver disease, the PAF was greatest for hepatitis C infection (33%; 95% CI 17-48). For renal disease, the PAF was greatest for hypertension (39%; 26-51) followed by elevated total cholesterol (22%; 13-31), detectable HIV RNA (19; 9-31), and low CD4 cell count (13%; 4-21)., Interpretation: The substantial proportion of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes that could be prevented with interventions on traditional risk factors elevates the importance of screening for these risk factors, improving the effectiveness of prevention (or modification) of these risk factors, and creating sustainable care models to implement such interventions during the decades of life of adults living with HIV who are receiving care., Funding: National Institutes of Health, US Centers for Disease Control and Prevention, the US Agency for Healthcare Research and Quality, the US Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long Term Care, and the Government of Alberta., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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. <35 mW/m = 1.62, 95% CI = 0.99 to 2.65). Current, lagged, and cumulative CD4 and HIV RNA were not associated with melanoma incidence. Melanoma incidence was higher among people ART-treated for a larger proportion of time in the previous 720 days (aHR per 10% increase = 1.16, 95% CI = 1.03 to 1.30)., Conclusions: These results suggest that HIV-induced immune dysfunction does not influence melanoma development. The association between ART and melanoma risk may be due to increased skin surveillance among PWH engaged in clinical care. Associations with age and UVB confirmed those established in the general population.

Background: Viral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non-AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses., Objective: To determine whether viral suppression is associated with decreased cancer risk., Design: Prospective cohort., Setting: Department of Veterans Affairs., Participants: HIV-positive veterans (n = 42 441) and demographically matched uninfected veterans (n = 104 712) from 1999 to 2015., Measurements: Standardized cancer incidence rates and Poisson regression rate ratios (RRs; HIV-positive vs. uninfected persons) by viral suppression status (unsuppressed: person-time with HIV RNA levels ≥500 copies/mL; early suppression: initial 2 years with HIV RNA levels <500 copies/mL; long-term suppression: person-time after early suppression with HIV RNA levels <500 copies/mL)., Results: Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 [95% CI, 2.19 to 2.51]), lower among persons with early suppression (RR, 1.99 [CI, 1.87 to 2.12]), and lowest among persons with long-term suppression (RR, 1.52 [CI, 1.44 to 1.61]). This trend was strongest for ADC (unsuppressed: RR, 22.73 [CI, 19.01 to 27.19]; early suppression: RR, 9.48 [CI, 7.78 to 11.55]; long-term suppression: RR, 2.22 [CI, 1.69 to 2.93]), much weaker for NADC caused by viruses (unsuppressed: RR, 3.82 [CI, 3.24 to 4.49]; early suppression: RR, 3.42 [CI, 2.95 to 3.97]; long-term suppression: RR, 3.17 [CI, 2.78 to 3.62]), and absent for NADC not caused by viruses., Limitation: Lower viral suppression thresholds, duration of long-term suppression, and effects of CD4+ and CD8+ T-cell counts were not thoroughly evaluated., Conclusion: Antiretroviral therapy resulting in long-term viral suppression may contribute to cancer prevention, to a greater degree for ADC than for NADC. Patients with long-term viral suppression still had excess cancer risk., Primary Funding Source: National Cancer Institute and National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.

Introduction: Despite major progress in controlling HIV disease through antiretroviral therapy, changes in immune phenotype and function persist in individuals with chronic HIV, raising questions about accelerated aging of the immune system., Methods: We conducted a cross-sectional study (2005-2007) of HIV-infected (n = 111) and uninfected (n = 114) men from the Veterans Aging Cohort Study. All HIV-infected subjects were on antiretroviral therapy with VL <400 copies/mL for at least 3 years. T-cell markers were examined using flow cytometry. We evaluated the impact of HIV serostatus and age on T-cell phenotypes (expressed as percentages of the total CD4 and CD8 T-cell population) using multivariate linear regression, adjusted for smoking, alcohol, and race/ethnicity. We tested for interactions between HIV and age by including interaction terms., Results: Among both HIV-infected and uninfected subjects, increasing age was associated with a decreased proportion of naive CD4 T cells (P = 0.014) and CD8 T cells (P < 0.0001). Both HIV infection and increasing age were associated with higher proportions of effector memory CD4 T cells (P < 0.0001 for HIV; P = 0.04 for age) and CD8 T cells (P = 0.0001 for HIV; P = 0.0004 for age). HIV infection, but not age, was associated with a higher proportion of activated CD8 T cells (P < 0.0001). For all T-cell subsets tested, there were no significant interactions between HIV infection and age., Conclusions: Age and HIV status independently altered the immune system, but we found no conclusive evidence that HIV infection and advancing age synergistically result in accelerated changes in age-associated T-cell markers among virally suppressed individuals.

Background: Monitoring cancer risk among HIV-infected people in the modern antiretroviral therapy (ART) era is essential given their elevated risk for many cancers and prolonged survival with immunosuppression, ART exposure, and ageing. We aimed to examine cancer risk in HIV-infected people in the USA as compared with that in the general population., Methods: We did a registry-linkage study with data from population-based HIV and cancer registries in the USA (the HIV/AIDS Cancer Match Study). We assessed a cohort of HIV-infected people identified in HIV registries in Colorado, Connecticut, Georgia, Maryland, Michigan, New Jersey, New York, Puerto Rico, and Texas from 1996 to 2012. Follow-up started 3 months after either the latest of the beginning of systematic name-based state HIV registration, HIV report date (or AIDS diagnosis, if this was earlier), start of cancer registration, or Jan 1, 1996, and ended at the earliest of either death, end of cancer-registry coverage, or Dec 31, 2012. We identified diagnoses of cancer in this population through linkage with corresponding cancer registries and calculated standardised incidence ratios (SIRs) to measure cancer risk in people with HIV compared with the USA general population, by dividing the observed number of cases in people with HIV by the expected number (estimated by applying general population cancer-incidence rates to person-time in the HIV population based on sex, age, race or ethnic group, calendar year, and registry). We tested SIR differences by AIDS status and over time using Poisson regression., Findings: Among 448 258 people with HIV (who contributed 3 093 033 person-years), 21 294 incident cancers were diagnosed during 1996-2012. In these people, compared with the general population, risk was elevated (p<0·0001 for all) for cancer overall (SIR 1·69, 95% CI 1·67-1·72), AIDS-defining cancers (Kaposi's sarcoma [498·11, 477·82-519·03], non-Hodgkin lymphoma [11·51, 11·14-11·89], and cervix [3·24, 2·94-3·56]), most other virus-related cancers (eg, anus [19·06, 18·13-20·03], liver [3·21, 3·02-3·41], and Hodgkin's lymphoma [7·70, 7·20-8·23]), and some virus-unrelated cancers (eg, lung [1·97, 1·89-2·05]), but not for other common cancers. Risk for several cancers was higher after AIDS onset and declined across calendar periods. After multivariable adjustment, SIRs decreased significantly across 1996-2012 for Kaposi's sarcoma, two subtypes of non-Hodgkin lymphoma, and cancer of the anus, liver, and lung, but remained elevated. SIRs did not increase over time for any cancer., Interpretation: For several virus-related cancers and lung cancer, declining risks over time in HIV-infected people probably reflect the expansion of ART since 1996. Additional efforts aimed at cancer prevention and screening in people with HIV are warranted., Funding: National Cancer Institute., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Cancer remains an important cause of morbidity and mortality in people with human immunodeficiency virus (PWHIV) on effective antiretroviral therapy (ART). Estimates of cancer-attributable mortality can inform public health efforts., Methods: We evaluated 46956 PWHIV receiving ART in North American HIV cohorts (1995-2009). Using information on incident cancers and deaths, we calculated population-attributable fractions (PAFs), estimating the proportion of deaths due to cancer. Calculations were based on proportional hazards models adjusted for age, sex, race, HIV risk group, calendar year, cohort, CD4 count, and viral load., Results: There were 1997 incident cancers and 8956 deaths during 267145 person-years of follow-up, and 11.9% of decedents had a prior cancer. An estimated 9.8% of deaths were attributable to cancer (cancer-attributable mortality rate 327 per 100000 person-years). PAFs were 2.6% for AIDS-defining cancers (ADCs, including non-Hodgkin lymphoma, 2.0% of deaths) and 7.1% for non-AIDS-defining cancers (NADCs: lung cancer, 2.3%; liver cancer, 0.9%). PAFs for NADCs were higher in males and increased strongly with age, reaching 12.5% in PWHIV aged 55+ years. Mortality rates attributable to ADCs and NADCs were highest for PWHIV with CD4 counts <100 cells/mm3. PAFs for NADCs increased during 1995-2009, reaching 10.1% in 2006-2009., Conclusions: Approximately 10% of deaths in PWHIV prescribed ART during 1995-2009 were attributable to cancer, but this fraction increased over time. A large proportion of cancer-attributable deaths were associated with non-Hodgkin lymphoma, lung cancer, and liver cancer. Deaths due to NADCs will likely grow in importance as AIDS mortality declines and PWHIV age., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: 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., Setting: North American AIDS Cohort Collaboration on Research and Design., Methods: 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., Results: In separate models, the relationship between each measure and KS risk was highly significant (P < 0.0001). Our final mutually adjusted model included recent CD4 count [hazard ratio (HR) for <50 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 was <0.0001. After adjusting for these measures, we did not detect an independent association between ART use and KS risk., Conclusions: 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.

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., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: HIV infection is independently associated with risk of lung cancer, but few data exist for the relation between longitudinal measurements of immune function and lung-cancer risk in people living with HIV., Methods: We followed up participants with HIV from the Veterans Aging Cohort Study for a minimum of 3 years between Jan 1, 1998, and Dec 31, 2012, and used cancer registry data to identify incident cases of lung cancer. The index date for each patient was the later of the date HIV care began or Jan 1, 1998. We excluded patients with less than 3 years' follow-up, prevalent diagnoses of lung cancer, or incomplete laboratory data. We used Cox regression models to investigate the relation between different time-updated lagged and cumulative exposures (CD4 cell count, CD8 cell count, CD4/CD8 ratio, HIV RNA, and bacterial pneumonia) and risk of lung cancer. Models were adjusted for age, race or ethnicity, smoking, hepatitis C virus infection, alcohol use disorders, drug use disorders, and history of chronic obstructive pulmonary disease and occupational lung disease., Findings: We identified 277 cases of incident lung cancer in 21 666 participants with HIV. In separate models for each time-updated 12 month lagged, 24 month simple moving average cumulative exposure, increased risk of lung cancer was associated with low CD4 cell count (p trend=0·001), low CD4/CD8 ratio (p trend=0·0001), high HIV RNA concentration (p=0·004), and more cumulative bacterial pneumonia episodes (12 month lag only; p trend=0·0004). In a mutually adjusted model including these factors, CD4/CD8 ratio and cumulative bacterial pneumonia episodes remained significant (p trends 0·003 and 0·004, respectively)., Interpretation: In our large HIV cohort in the antiretroviral therapy era, we found evidence that dysfunctional immune activation and chronic inflammation contribute to the development of lung cancer in the setting of HIV infection. These findings could be used to target lung-cancer prevention measures to high-risk groups., Funding: US National Institutes of Health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Utilizing the Veterans Aging Cohort Study, the largest HIV cohort in North America, we conducted one of the few comprehensive comparisons of cancer incidence time trends in HIV-infected (HIV+) versus uninfected persons during the antiretroviral therapy (ART) era., Design: Prospective cohort study., Methods: We followed 44 787 HIV+ and 96 852 demographically matched uninfected persons during 1997-2012. We calculated age-, sex-, and race/ethnicity-standardized incidence rates and incidence rate ratios (IRR, HIV+ versus uninfected) over four calendar periods with incidence rate and IRR period trend P values for cancer groupings and specific cancer types., Results: We observed 3714 incident cancer diagnoses in HIV+ and 5760 in uninfected persons. The HIV+ all-cancer crude incidence rate increased between 1997-2000 and 2009-2012 (P trend = 0.0019). However, after standardization, we observed highly significant HIV+ incidence rate declines for all cancer (25% decline; P trend <0.0001), AIDS-defining cancers (55% decline; P trend <0.0001), nonAIDS-defining cancers (NADC; 15% decline; P trend = 0.0003), and nonvirus-related NADC (20% decline; P trend <0.0001); significant IRR declines for all cancer (from 2.0 to 1.6; P trend <0.0001), AIDS-defining cancers (from 19 to 5.5; P trend <0.0001), and nonvirus-related NADC (from 1.4 to 1.2; P trend = 0.049); and borderline significant IRR declines for NADC (from 1.6 to 1.4; P trend = 0.078) and virus-related NADC (from 4.9 to 3.5; P trend = 0.071)., Conclusion: Improved HIV care resulting in improved immune function most likely contributed to the HIV+ incidence rate and the IRR declines. Further promotion of early and sustained ART, improved ART regimens, reduction of traditional cancer risk factor (e.g. smoking) prevalence, and evidence-based screening could contribute to future cancer incidence declines among HIV+ persons.

Objective: The burden of cancer among persons living with HIV/AIDS (PLWHA) is substantial and increasing. We assessed the prevalence of modifiable cancer risk factors among adult PLWHA in Western high-income countries since 2000., Design: Meta-analysis., Methods: We searched PubMed to identify articles published in 2011-2013 reporting prevalence of smoking, alcohol consumption, overweight/obesity, and infection with human papillomavirus (HPV), hepatitis C virus (HCV) and hepatitis B virus (HBV) among PLWHA. We conducted random effects meta-analyses of prevalence for each risk factor, including estimation of overall, sex-specific, and HIV-transmission-group-specific prevalence. We compared prevalence in PLWHA with published prevalence estimates in US adults., Results: The meta-analysis included 113 publications. Overall summary prevalence estimates were current smoking, 54% [95% confidence interval (CI) 49-59%] versus 20-23% in US adults; cervical high-risk HPV infection, 46% (95% CI 34-58%) versus 29% in US females; oral high-risk HPV infection, 16% (95% CI 10-23%) versus 4% in US adults; anal high-risk HPV infection (men who have sex with men), 68% (95% CI 57-79%), with no comparison estimate available; chronic HCV infection, 26% (95% CI 21-30%) versus 0.9% in US adults; and HBV infection, 5% (95% CI 4-5%) versus 0.3% in US adults. Overweight/obesity prevalence (53%; 95% CI 46-59%) was below that of US adults (68%). Meta-analysis of alcohol consumption prevalence was impeded by varying assessment methods. Overall, we observed considerable study heterogeneity in prevalence estimates., Conclusion: Prevalence of smoking and oncogenic virus infections continues to be extraordinarily high among PLWHA, indicating a vital need for risk factor reduction efforts.

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.

Background: Although it has been shown that human immunodeficiency virus (HIV)-infected adults are at greater risk for aging-associated events, it remains unclear as to whether these events happen at similar, or younger ages, in HIV-infected compared with uninfected adults. The objective of this study was to compare the median age at, and risk of, incident diagnosis of 3 age-associated diseases in HIV-infected and demographically similar uninfected adults., Methods: The study was nested in the clinical prospective Veterans Aging Cohort Study of HIV-infected and demographically matched uninfected veterans, from 1 April 2003 to 31 December 2010. The outcomes were validated diagnoses of myocardial infarction (MI), end-stage renal disease (ESRD), and non-AIDS-defining cancer (NADC). Differences in mean age at, and risk of, diagnosis by HIV status were estimated using multivariate linear regression models and Cox proportional hazards models, respectively., Results: A total of 98 687 (31% HIV-infected and 69% uninfected) adults contributed >450 000 person-years and 689 MI, 1135 ESRD, and 4179 NADC incident diagnoses. Mean age at MI (adjusted mean difference, -0.11; 95% confidence interval [CI], -.59 to .37 years) and NADC (adjusted mean difference, -0.10 [95% CI, -.30 to .10] years) did not differ by HIV status. HIV-infected adults were diagnosed with ESRD at an average age of 5.5 months younger than uninfected adults (adjusted mean difference, -0.46 [95% CI, -.86 to -.07] years). HIV-infected adults had a greater risk of all 3 outcomes compared with uninfected adults after accounting for important confounders., Conclusions: HIV-infected adults had a higher risk of these age-associated events, but they occurred at similar ages than those without HIV., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To examine the risk and trends of HPV-related and HPV-unrelated Head and Neck Squamous Cell Carcinoma (HNSCC) in HIV-infected individuals and assess whether immunosuppression (measured through CD4 cell count) and other risk factors impact HNSCC risk., Materials and Methods: Incident HNSCCs at HPV-related and HPV-unrelated anatomic sites were detected in HIV-infected participants from pooled data from 17 prospective studies in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) between 1996 and 2009. HNSCC cases were validated using chart review or cancer registry matching. Risk factors for incident HPV-related and HPV-unrelated HNSCC were explored using mixed effects Poisson regression in a full prospective analysis, and the effect of CD4 prior to cancer diagnosis was examined in a nested case control analysis., Results: 66 HPV-related and 182 HPV-unrelated incident HNSCCs were detected among 82,375 HIV-infected participants. Standardized incidence ratios (SIRs) for both HPV-related (SIR=3.2, 95%CI=2.5-3.4) and HPV-unrelated (SIR=3.0, 95%CI=2.5-4.1) HNSCC were significantly elevated in HIV-infected individuals compared with the US general population. Between 1996 and 2009, the age-standardized HPV-related HNSCC incidence increased non-significantly from 6.8 to 11.4per 100,000 person-years (p-trend=0.31) while the age-standardized incidence of HPV-unrelated HNSCC decreased non-significantly from 41.9 to 29.3 per 100,000 person-years (p-trend=0.16). Lower CD4 cell count prior to cancer diagnosis was significantly associated with increased HPV-related and HPV-unrelated HNSCC risk., Conclusion: The standardized incidence of HPV-related and HPV-unrelated HNSCC are both elevated in HIV-infected individuals. Immunosuppression may have a role in the development of both HPV-related and HPV-unrelated HNSCC., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The incidence and determinants of hepatic decompensation have been incompletely examined among patients co-infected with HIV and hepatitis C virus (HCV) in the antiretroviral therapy (ART) era, and few studies have compared outcome rates with those of patients with chronic HCV alone., Objective: To compare the incidence of hepatic decompensation between antiretroviral-treated patients co-infected with HIV and HCV and HCV-monoinfected patients and to evaluate factors associated with decompensation among co-infected patients receiving ART., Design: Retrospective cohort study., Setting: Veterans Health Administration., Patients: 4280 co-infected patients who initiated ART and 6079 HCV-monoinfected patients receiving care between 1997 and 2010. All patients had detectable HCV RNA and were HCV treatment-naive., Measurements: Incident hepatic decompensation, determined by diagnoses of ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage., Results: The incidence of hepatic decompensation was greater among co-infected than monoinfected patients (7.4% vs. 4.8% at 10 years; P < 0.001). Compared with HCV-monoinfected patients, co-infected patients had a higher rate of hepatic decompensation (hazard ratio [HR] accounting for competing risks, 1.56 [95% CI, 1.31 to 1.86]). Co-infected patients who maintained HIV RNA levels less than 1000 copies/mL still had higher rates of decompensation than HCV-monoinfected patients (HR, 1.44 [CI, 1.05 to 1.99]). Baseline advanced hepatic fibrosis (FIB-4 score >3.25) (HR, 5.45 [CI, 3.79 to 7.84]), baseline hemoglobin level less than 100 g/L (HR, 2.24 [CI, 1.20 to 4.20]), diabetes mellitus (HR, 1.88 [CI, 1.38 to 2.56]), and nonblack race (HR, 2.12 [CI, 1.65 to 2.72]) were each associated with higher rates of decompensation among co-infected patients., Limitation: Observational study of predominantly male patients., Conclusion: Despite receiving ART, patients co-infected with HIV and HCV had higher rates of hepatic decompensation than HCV-monoinfected patients. Rates of decompensation were higher for co-infected patients with advanced liver fibrosis, severe anemia, diabetes, and nonblack race., Primary Funding Source: National Institutes of Health.

India's National AIDS Control Organization provides free antiretroviral treatment (ART) to people living with HIV (PLHIV), including members of marginalized groups such as injecting drug users (IDUs). To help inform development of interventions to enhance ART access, we explored barriers to free ART access at government ART centers for IDUs living with HIV in Chennai by conducting three focus groups (n = 19 IDUs) and four key informant interviews. Data were explored using framework analysis to identify categories and derive themes. We found interrelated barriers at the family and social, health-care system, and individual levels. Family and social level barriers included lack of family support and fear of societal discrimination, as well as unmet basic needs, including food and shelter. Health-care system barriers included actual or perceived unfriendly hospital environment and procedures such as requiring proof of address and identity from PLHIV, including homeless IDUs; provider perception that IDUs will not adhere to ART, resulting in ART not being initiated; actual or perceived inadequate counseling services and lack of confidentiality; and lack of effective linkages between ART centers, needle/syringe programs, and drug dependence treatment centers. Individual-level barriers included active drug use, lack of self-efficacy in ART adherence, low motivation to initiate ART stemming from a fatalistic attitude, and inadequate knowledge about ART. These findings indicate that to facilitate IDUs gaining access to ART, systemic changes are needed, including steps to make the environment and procedures at government ART centers more IDU-friendly and steps to decrease HIV- and drug use-related stigma and discrimination faced by IDUs from the general public and health-care providers. Housing support for homeless IDUs and linkage of IDUs with drug dependence treatment are also essential.

Purpose of Review: To critically appraise recent published literature about factors associated with cancer risk likely to be influenced by combination antiretroviral therapy (cART) in HIV-infected individuals, and the potential of earlier cART initiation to reduce this risk., Recent Findings: Factors leading to increased risk of non-AIDS-defining malignancies (NADMs) in particular remain poorly understood. Immunodeficiency appears to be key, whereas evidence is emerging that a direct pro-oncogenic effect of HIV, activated inflammatory and coagulation pathways, and cART toxicity may also contribute. By reducing HIV replication, improving immune function, and limiting chronic inflammation, cART initiation at higher CD4 cell counts may, therefore, reduce NADM risk. However, cART only partly normalizes enhanced inflammation and coagulation seen during HIV infection and conflicting laboratory and epidemiological data have been reported as to whether (and how) cART affects NADM risk. Furthermore, secondary analyses of randomized controlled trials comparing early versus delayed cART initiation were inconclusive., Summary: Continuous epidemiological surveillance is warranted to monitor trends in cancer incidence among HIV-infected individuals and to better understand the impact of earlier cART on NADM risk. The role of adjuvant anti-inflammatory or antithrombotic therapies to reduce cancer risk deserves further investigation.

Background: We conducted a population-based study to evaluate whether non-small cell lung cancer (NSCLC) prognosis was worse in HIV-infected compared with HIV-uninfected patients., Methods: Using the Surveillance, Epidemiology and End Results (SEER) registry linked to Medicare claims, we identified 267 HIV-infected patients and 1428 similar controls with no evidence of HIV diagnosed with NSCLC between 1996 and 2007. We used conditional probability function (CPF) analyses to compare survival by HIV status accounting for an increased risk of non-lung cancer death (competing risks) in HIV-infected patients. We used multivariable CPF regression to evaluate lung cancer prognosis by HIV status adjusted for confounders., Results: Stage at presentation and use of stage-appropriate lung cancer treatment did not differ by HIV status. Median survival was 6 months (95% confidence interval (CI): 5-8 months) among HIV-infected NSCLC patients compared with 20 months (95% CI: 17-23 months) in patients without evidence of HIV. Multivariable CPF regression showed that HIV was associated with a greater risk of lung cancer-specific death after controlling for confounders and competing risks., Conclusion: NSCLC patients with HIV have a poorer prognosis than patients without evidence of HIV. NSCLC may exhibit more aggressive behaviour in the setting of HIV.

Objective: HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic human papillomavirus 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., Methods: Data were obtained from HIV-infected and -uninfected female participants in the North American AIDS Cohort Collaboration on Research and Design with no history of ICC at enrollment. Participants were followed from study entry or January 1996 through ICC, loss to follow-up, or December 2010. The relationship of HIV infection and CD4+ T-cell count with risk of ICC was assessed using age-adjusted Poisson regression models and standardized incidence ratios. All cases were confirmed by cancer registry records and/or pathology reports. Cervical cytology screening history was assessed through medical record abstraction., Results: A total of 13,690 HIV-infected and 12,021 HIV-uninfected women contributed 66,249 and 70,815 person-years of observation, respectively. Incident ICC was diagnosed in 17 HIV-infected and 4 HIV-uninfected women (incidence rate of 26 and 6 per 100,000 person-years, respectively). HIV-infected women with baseline CD4+ T-cells of ≥350, 200-349, and <200 cells per microliter had a 2.3, 3.0, and 7.7 times increase in ICC incidence, respectively, compared with HIV-uninfected women (P(trend) = 0.001). Of the 17 HIV-infected women, medical records for the 5 years before diagnosis showed that 6 had no documented screening, 5 had screening with low-grade or normal results, and 6 had high-grade results., Conclusions: This study found elevated incidence of ICC in HIV-infected compared with -uninfected women, and these rates increased with immunosuppression.

Purpose of Review: Combination antiretroviral therapy (ART) has turned HIV infection into a complex chronic disease. This article documents cancer risk among HIV-infected persons, reviews immune system effects of HIV infection in relation to cancer risk, discusses implications for cancer prevention, and suggests future research directions., Recent Findings: There has been a shift in the cancer spectrum from AIDS-defining cancers (ADC) to non-ADC, although the burden of ADC remains high. Although a high prevalence of non-HIV cancer risk factors among HIV-infected persons contributes to cancer risk, substantial evidence has accumulated in favor of an independent association between HIV-induced immunodeficiency and elevated risk of many specific cancer types, most of viral cause, although further work is needed to disentangle immunodeficiency and smoking effects for lung cancer, and immunodeficiency and hepatitis virus effects for liver cancer. Relationships between cancer risk and two other immune system hallmarks of HIV infection, chronic inflammation, and immune dysfunction/senescence, remain poorly understood., Summary: Early, sustained ART is a crucial component of cancer prevention. Continued epidemiologic monitoring is needed to detect possible effects on cancer risk of specific ART classes or medications, long-term exposure to systemic inflammation or immune dysfunction, or earlier or more effective ART.

Background: It is unclear whether the elevated rate of lung cancer among HIV-infected persons is due to biological effects of HIV, surveillance bias, or excess smoking. We compared the incidence of lung cancer between HIV-infected and demographically similar HIV-uninfected patients, accounting for smoking and stage of lung cancer at diagnosis., Design: Data from the Veterans Aging Cohort Study Virtual Cohort were linked to data from the Veterans Affairs Central Cancer Registry, resulting in an analytic cohort of 37,294 HIV-infected patients and 75,750 uninfected patients., Methods: We calculated incidence rates of pathologically confirmed lung cancer by dividing numbers of cases by numbers of person-years at risk. We used Poisson regression to determine incidence rate ratios (IRRs), adjusting for age, sex, race/ethnicity, smoking prevalence, previous bacterial pneumonia, and chronic obstructive pulmonary disease., Results: The incidence rate of lung cancer in HIV-infected patients was 204 cases per 100,000 person-years [95% confidence interval (CI) 167-249] and among uninfected patients was 119 cases per 100,000 person-years (95% CI 110-129). The IRR of lung cancer associated with HIV infection remained significant after multivariable adjustment (IRR 1.7; 95% CI 1.5-1.9). Lung cancer stage at presentation did not differ between HIV-infected and uninfected patients., Conclusion: In our cohort of demographically similar HIV-infected and uninfected patients, HIV infection was an independent risk factor for lung cancer after controlling for potential confounders including smoking. The similar stage distribution between the two groups indicated that surveillance bias was an unlikely explanation for this finding.

Background: Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends., Methods: In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men)., Results: Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7-151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5-61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8-6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5-2.2). In comparison with the period 2000-2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3-.9) in 1996-1999 and 0.9 (95% CI, .6-1.2) in 2004-2007., Conclusions: Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.

The Indian government provides free antiretroviral treatment (ART) for people living with HIV. To assist in developing policies and programs to advance equity in ART access, we explored barriers to ART access among kothis (men who have sex with men [MSM] whose gender expression is feminine) and aravanis (transgender women, also known as hijras) living with HIV in Chennai. In the last quarter of 2007, we conducted six focus groups and four key-informant interviews. Data were explored using framework analysis to identify categories and derive themes. We identified barriers to ART access at the family/social-level, health care system-level, and individual-level; however, we found these barriers to be highly interrelated. The primary individual-level barrier was integrally linked to the family/social and health care levels: many kothis and aravanis feared serious adverse consequences if their HIV-positive status were revealed to others. Strong motivations to keep one's HIV-positive status and same-sex attraction secret were interconnected with sexual prejudice against MSM and transgenders, and HIV stigma prevalent in families, the health care system, and the larger society. HIV stigma was present within kothi and aravani communities as well. Consequences of disclosure, including rejection by family, eviction from home, social isolation, loss of subsistence income, and maltreatment (although improving) within the health care system, presented powerful disincentives to accessing ART. Given the multi-level barriers to ART access related to stigma and discrimination, interventions to facilitate ART uptake should address multiple constituencies: the general public, health care providers, and the kothi and aravani communities. India needs a national policy and action plan to address barriers to ART access at family/social, health care system, and individual levels for aravanis, kothis, other subgroups of MSM and other marginalized groups.

Background: Few studies have compared cancer risk between HIV-infected individuals and a demographically similar HIV-uninfected internal comparison group, adjusting for cancer risk factors., Methods: We followed 20,775 HIV-infected and 215,158 HIV-uninfected individuals enrolled in Kaiser Permanente (KP) California for incident cancer from 1996 to 2008. Rate ratios (RR) were obtained from Poisson models comparing HIV-infected (overall and stratified by recent CD4 count and HIV RNA) with HIV-uninfected individuals, adjusted for age, sex, race/ethnicity, calendar period, KP region, smoking, alcohol/drug abuse, and overweight/obesity., Results: We observed elevated RRs for Kaposi sarcoma (KS; RR = 199; P < 0.001), non-Hodgkin lymphoma (NHL; RR = 15; P < 0.001), anal cancer (RR = 55; P < 0.001), Hodgkin lymphoma (HL; RR = 19; P < 0.001), melanoma (RR = 1.8; P = 0.001), and liver cancer (RR = 1.8; P = 0.013), a reduced RR for prostate cancer (RR = 0.8; P = 0.012), and no increased risk for oral cavity/pharynx (RR = 1.4; P = 0.14), lung (RR = 1.2; P = 0.15), or colorectal (RR = 0.9; P = 0.34) cancers. Lung and oral cavity/pharynx cancers were elevated for HIV-infected subjects in models adjusted only for demographics. KS, NHL, anal cancer, HL, and colorectal cancer had significant (P < 0.05) trends for increasing RRs with decreasing recent CD4. The RRs for lung and oral cavity/pharynx cancer were significantly elevated with CD4 < 200 cells/μL and for melanoma and liver cancer with CD4 < 500 cells/μL. Only KS and NHL were associated with HIV RNA., Conclusion: Immunodeficiency was positively associated with all cancers examined except prostate cancer among HIV-infected compared with HIV-uninfected individuals, after adjustment for several cancer risk factors., Impact: Earlier antiretroviral therapy initiation to maintain high CD4 levels might reduce the burden of cancer in this population.

Background: Chronic inflammation caused by hepatitis B virus infection, hepatitis C virus infection, and/or heavy alcohol use can lead to fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). FIB-4 is an index score calculated from platelet count, alanine transaminase, aspartate transaminase, and age that predicts fibrosis and cirrhosis. We hypothesized that high FIB-4 would be associated with development of HCC in HIV-infected persons, who are at high risk due to high prevalence of viral hepatitis and alcohol consumption, and possibly due to HIV infection itself., Methods: Using proportional hazards models, we tested this hypothesis among 22,980 HIV-infected men from the Veterans Aging Cohort Study. We identified incident HCC cases from the Veterans Affairs Central Cancer Registry., Results: During follow-up, there were 112 incident HCC diagnoses. The age- and race/ethnic group-adjusted HR was 4.2 [95% confidence interval (CI), 2.4-7.4] for intermediate FIB-4 and 13.0 (95% CI, 7.2-23.4) for high FIB-4, compared with low FIB-4. After further adjustment for enrollment year, CD4 count, HIV-1 RNA level, antiretroviral therapy use, hepatitis B and C virus infection, alcohol abuse/dependency, and diabetes, FIB-4 remained a strong, significant, independent risk factor for HCC. The multivariate-adjusted HR was 3.6 (95% CI, 2.1-6.4) for intermediate FIB-4 and 9.6 (95% CI, 5.2-17.4) for high FIB-4., Conclusions: Calculated from routine, noninvasive laboratory tests, FIB-4 is a strong, independent HCC risk factor in HIV-infected patients., Impact: FIB-4 might prove valuable as an easily measured index to identify those at highest risk for HCC, even prior to development of clinical cirrhosis.

Non-AIDS-defining cancers are a rising health concern among HIV-infected patients. Cancer screening is now an important component of health maintenance in HIV clinical practice. The decision to screen an HIV-infected patient for cancer should include an assessment of individualized risk for the particular cancer, life expectancy, and the harms and benefits associated with the screening test and its potential outcome. HIV-infected patients are at enhanced risk of several cancers compared to the general population; anal cancer, hepatocellular carcinoma, Hodgkin's lymphoma, and lung cancer all have good evidence demonstrating an enhanced risk in HIV-infected persons. A number of cancer screening interventions have shown benefit for specific cancers in the general population, but data on the application of these tests to HIV-infected persons are limited. Here we review the epidemiology and background literature relating to cancer screening interventions in HIV-infected persons. We then use these data to inform a conceptual model for evaluating HIV-infected patients for cancer screening.

Objective: To describe the prevalence and correlates of dual-contraceptive methods use (condoms and an effective pregnancy prevention method) and barriers to their use among married persons living with HIV (PLHIV) in India., Methods: We conducted a quantitative survey (93 men, 97 women), 25 in-depth interviews, seven focus groups, and five key informant interviews., Results: Prevalence of dual-contraceptive method use increased from 5% before HIV diagnosis to 23% after diagnosis (P < 0.001). Condoms were the most common contraceptive method, with prevalence increasing from 13% before diagnosis to 92% after diagnosis (P < 0.001). Barriers to using noncondom contraceptives were lack of discussion about noncondom contraceptives by health care providers, lack of acceptability of noncondom contraceptives among PLHIV, and lack of involvement of husbands in family planning counseling., Conclusion: There is a need for interventions, including training of health care providers, to increase dual-contraceptive methods use among married PLHIV.

This investigation examined sexual behaviors among heterosexual persons living with HIV (PLHIV) in India. Study participants (mostly married) were interviewed during August to November 2006 in five Indian states using a quantitative survey (n = 100 men and 100 women), eight focus groups (n = 58 participants), and in-depth interviews (n = 31). One third of men and one fourth of women reported inconsistent condom use with regular sexual partners. Facilitators of condom use with regular partners included a feeling of personal responsibility to protect the health of the partner, desire to prevent acquisition and/or transmission of sexually transmitted infections, and the belief that condoms are needed for antiretroviral therapy to be effective. Barriers to consistent condom use with regular partners included the belief that condoms are unnecessary in HIV-positive seroconcordant relationships; lack of sexual satisfaction with condoms; the desire to have a child; husband's alcohol use, depression, and anxiety; fear that disclosure of HIV status will bring marital discord and family shame; and inadequate counseling by health care providers. Positive prevention programs should include counseling about benefits of safer sex in HIV-positive seroconcordant relationships, counseling about integrating condom use with sexual satisfaction and intimacy, condom use self-efficacy and negotiation skills-building, family planning counseling, mental health and alcohol dependence treatment, and counseling and skills-building about disclosure. Health care providers must be trained to provide these services. Furthermore, efforts are needed to promote tolerance for family planning choices made by couples and to counter the stigma associated with HIV/AIDS and condoms in the broader society.

Acute/early HIV infection is a period of high risk for HIV transmission. Better understanding of behavioral aspects during this period could improve interventions to limit further transmission. Thirty-four participants with acute/early HIV infection from six US cities were assessed with the Mini International Diagnostic Interview, Beck Depression Inventory II, State-Trait Anxiety Inventory, Brief COPE, and an in-depth interview. Most had a pre-HIV history of alcohol or substance use disorder (85%); a majority (53%) had a history of major depressive or bipolar disorder. However, post-diagnosis coping was predominantly adaptive, with only mild to moderate elevations of anxious or depressive mood. Respondents described challenges managing HIV in tandem with pre-existing substance abuse problems, depression, and anxiety. Integration into medical and community services was associated with adaptive coping. The psychiatric context of acute/early HIV infection may be a precursor to infection, but not necessarily a barrier to intervention to reduce forward transmission of HIV among persons newly infected.

Acute/early HIV infection is a period of high HIV transmission. Consequently, early detection of HIV infection and targeted HIV prevention could prevent a significant proportion of new transmissions. As part of an NIMH-funded multisite study, we used in-depth interviews to explore understandings of acute HIV infection (AHI) among 34 individuals diagnosed with acute/early HIV infection in six US cities. We found a marked lack of awareness of AHI-related acute retroviral symptoms and a lack of clarity about AHI testing methods. Most participants knew little about the meaning and/or consequences of AHI, particularly that it is a period of elevated infectiousness. Over time and after the acute stage of infection, many participants acquired understanding of AHI from varied sources, including the Internet, HIV-infected friends, and health clinic employees. There is a need to promote targeted education about AHI to reduce the rapid spread of HIV associated with acute/early infection within communities at risk for HIV.

Acute/early HIV infection is a period of heightened HIV transmission and a window of opportunity for intervention to prevent onward disease transmission. The NIMH Multisite Acute HIV Infection (AHI) Study was an exploratory initiative aimed at determining the feasibility of recruiting persons with AHI into research, assessing their psychosocial and behavioral characteristics, and examining short-term changes in these characteristics. This paper reports on lessons learned in the study, including: (1) the need to establish the cost-effectiveness of AHI testing; (2) challenges to identifying persons with AHI; (3) the need to increase awareness of acute-phase HIV transmission risks; (4) determining the goals of behavioral interventions following AHI diagnosis; and (5) the need for "rapid response" public health systems that can move quickly enough to intervene while persons are still in the AHI stage. There are untapped opportunities for behavioral and medical science collaborations in these areas that could reduce the incidence of HIV infection.

Acute/early HIV infection plays a critical role in onward HIV transmission. Detection of HIV infections during this period provides an important early opportunity to offer interventions which may prevent further transmission. In six US cities, persons with acute/early HIV infection were identified using either HIV RNA testing of pooled sera from persons screened HIV antibody negative or through clinical referral of persons with acute or early infections. Fifty-one cases were identified and 34 (68%) were enrolled into the study; 28 (82%) were acute infections and 6 (18%) were early infections. Of those enrolled, 13 (38%) were identified through HIV pooled testing of 7,633 HIV antibody negative sera and 21 (62%) through referral. Both strategies identified cases that would have been missed under current HIV testing and counseling protocols. Efforts to identify newly infected persons should target specific populations and geographic areas based on knowledge of the local epidemiology of incident infections.

Risk reductions behaviors are especially important during acute/early HIV infection, a period of high transmission risk. We examined how sexual behaviors changed following diagnosis of acute/early HIV infection. Twenty-eight individuals completed structured surveys and in-depth interviews shortly after learning of their infection and 2 months later. Quantitative analyses revealed significant changes after diagnosis, including reductions in total partners and decreases in the proportion of unprotected sex acts occurring with uninfected partners (serosorting). Qualitative findings indicated that these changes were motivated by concerns about infecting others. However, participants were less successful at increasing the frequency with which they used condoms. These results suggest that the initial diagnosis with HIV may constitute an important component of interventions to promote risk reduction during the acute/early stages of the disease.

India's National AIDS Control Organization (NACO) provides free first-line antiretroviral treatment (ART) at government centers for people living with HIV. To assist in developing policies and programs to ensure equity in ART access, we explored barriers to ART access among female sex workers (FSWs) living with HIV in Chennai. Between August and November 2007, we conducted three focus group discussions and two key informant interviews. Data were explored using framework analysis to identify categories and derive themes. We found interrelated barriers at the family/social, health care system/programmatic, and individual levels. Major barriers included fear of adverse consequences of disclosure of HIV status due to stigma and discrimination associated with HIV and sex work, lack of family support, negative experiences with health care providers, lack of adequate counseling services at government centers and by outreach workers employed by nongovernmental organizations (NGOs), perceived biased treatment of FSWs who are not referred by NGOs, lack of adequate knowledge about ART, and fatalism. Barriers can be addressed by: creating effective measures to reduce stigma associated with HIV/AIDS and sex work at the familial, societal, and health care system levels; incorporating information about ART into targeted interventions among FSWs; training counselors at government hospitals and NGO outreach workers on treatment issues; improving infrastructure and staffing levels at government centers to allow adequate time and privacy for counseling; and implementing government mass media campaigns on ART availability. Finally, it is crucial that NACO begin monitoring ART coverage of FSWs and other marginalized populations to ensure equitable ART access.

Acute HIV infection (AHI) is the earliest stage of HIV disease, when plasma HIV viremia, but not HIV antibodies, can be detected. Acute HIV infection often presents as a nonspecific viral syndrome. However, its diagnosis, which enables linkage to early medical care and limits further HIV transmission, is seldom made. We describe the experience of Yale's Center for Interdisciplinary Research on AIDS with AHI diagnosis in Connecticut, as a participating center in the National Institute of Mental Health Multisite AHI Study. We sought to identify AHI cases by clinical referrals and by screening for AHI at two substance abuse care facilities and an STD clinic. We identified one case by referral and one through screening of 590 persons. Screening for AHI is feasible and probably cost effective. Primary care providers should include AHI in the differential diagnosis when patients present with a nonspecific viral syndrome.

There are few peer-reviewed studies of HIV/AIDS-related knowledge, attitudes, beliefs and practices among adolescents in Central America. A population-based cross-sectional survey was conducted among 246 adolescents in León, Nicaragua, where there is reason for concern about a rise in HIV infections. In many respects, León adolescents were typical of those in other Latin American countries, with a mixture of correct and incorrect knowledge about transmission of HIV and sexually transmitted infections, a higher proportion of males than females reporting having had sex or using condoms, and inconsistent condom use. While some sexual attitudes conformed to the ideology of machismo, others did not, providing an opening for prevention interventions. Some dimensions of HIV/AIDS stigma were high, and most adolescents disapproved of same-sex sexual behaviour. Intervention against homosexuality-related stigma is particularly urgent because a concentrated HIV epidemic may be emerging in Nicaragua among men who have sex with men. Personal religious beliefs did not appear to pose a barrier to condom use. In a multivariate model, being out of school was a significant correlate of having had sex and of insufficient HIV/AIDS-related knowledge. Accordingly, HIV prevention interventions must reach adolescents both in and out of school. A multi-component approach to prevention is needed, including programmes based in schools, communities, the mass media and health facilities.

This study assessed the extent and correlates of the practice of engaging in unprotected intercourse for extra money among commercial sex workers (CSWs) in Kinshasa, Democratic Republic of the Congo. We conducted a cross-sectional survey using a structured, interviewer-administered questionnaire among a convenience sample of 136 CSWs. More than one-quarter of CSWs (26.5%) engaged in unprotected intercourse for extra money. These CSWs charged about 3.5 times more for unprotected intercourse than for protected intercourse. Multivariate logistic regression showed that CSWs who engaged in unprotected intercourse for extra money were significantly more likely to live or work in non-downtown (lower socioeconomic) areas of Kinshasa (odds ratio [OR] = 3.07), to have at least one child less than six years of age (OR = 2.95), and to know other CSWs who engaged in the same practice (OR = 9.38). We hypothesize that desperate socioeconomic conditions combined with peer/social norms drive the practice of engaging in unprotected intercourse for extra money. Additional circumstances under which Kinshasa CSWs engaged in unprotected intercourse included intercourse with clients who tore their condoms to increase sexual pleasure (58.8% of CSWs), episodes of condom failure (56.8% of CSWs), and unprotected intercourse with regular noncommercial partners (only 5.3% of CSWs with noncommercial partners always used condoms with these partners).