Purpose: Actinic keratoses (AK) diagnosis, billing, and pharmacy codes have not been validated among people living with human immunodeficiency virus (HIV), preventing use in epidemiologic and clinical research. We aimed to calculate the positive predictive value of AK diagnosis codes, procedural codes for destruction of pre-malignant lesions, and pharmacy codes for topical 5-fluorouracil. Methods: Patients diagnosed with HIV within the Infectious Disease clinic at the Atlanta Veterans Affairs Medical Center from 1/1/2002 to 8/5/2017 were eligible. Patients were included if they had any of the following: encounters with a diagnosis for AK (International Classification of Diseases-9: 702.0; ICD-10: L57.0), procedural codes for destruction of premalignant lesions (Current Procedural Terminology (CPT): 17000, 17003, and 17004), and prescriptions for topical 5-fluorouracil. PPV and binomial 95% confidence intervals were calculated. Results: PPV was 91.9% (89.1–94.7) for 369 encounters with an AK diagnosis. For procedural codes, PPV was 52.6% (48.1–57.2) for 454 encounters with destruction of 1 pre-malignant lesion, 63.7% (58.4–68.9) for 322 encounters with destruction of 2–14 lesions, and 57.7% (38.7–76.7) for 26 encounters with destruction of 15+ lesions. PPV was 72.9% (63.5–82.4) for 85 encounters with a prescription of topical 5-fluorouracil. Conclusion: AK diagnosis codes are appropriate to use in epidemiologic and health policy research among people living with HIV and may be more reliable than destruction of pre-malignant lesion CPT codes.

Purpose: The U.S. HIV epidemic has become a public health issue that increasingly affects men who have sex with men (MSM), including those residing in nonurban areas. Increasing access to pre-exposure prophylaxis (PrEP) in nonurban areas will prevent HIV acquisition and could address the growing HIV epidemic. No studies have quantified the associations between PrEP access and PrEP use among nonurban MSM. Methods: Using 2020 PrEP Locator data and American Men’s Internet Survey data, we conducted multilevel log-binomial regression to examine the association between area-level geographic accessibility of PrEP-providing clinics and individual-level PrEP use among MSM residing in nonurban areas in the U.S. Findings: Of 4,792 PrEP-eligible nonurban MSM, 20.1% resided in a PrEP desert (defined as more than a 30-minute drive to access PrEP), and 15.2% used PrEP in the past 12 months. In adjusted models, suburban MSM residing in PrEP deserts were less likely to use PrEP in the past year (adjusted prevalence ratio (aPR) = 0.35; 95% confidence interval (CI) = 0.15, 0.80) than suburban MSM not residing in PrEP deserts, and other nonurban MSM residing in PrEP deserts were less likely to use PrEP in the past year (aPR = 0.75; 95% CI = 0.60, 0.95) than other nonurban MSM not residing in PrEP deserts. Conclusions: Structural interventions designed to decrease barriers to PrEP access that are unique to nonurban areas in the U.S. are needed to address the growing HIV epidemic in these communities.

Background: The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards. Methods: We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population. Findings: Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35·8 years (95% CI 35·2–36·4) of life left if they started ART before 2015, and 39·0 years (38·5–39·5) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34·5 years (33·8–35·2) and 37·0 (36·5–37·6). Women with CD4 counts of fewer than 49 cells per μL at the start of follow-up had an estimated 19·4 years (18·2–20·5) of life left at age 40 years if they started ART before 2015 and 24·9 years (23·9–25·9) left if they started ART after 2015. The corresponding estimates for men were 18·2 years (17·1–19·4) and 23·7 years (22·7–24·8). Women with CD4 counts of at least 500 cells per μL at the start of follow-up had an estimated 40·2 years (39·7–40·6) of life left at age 40 years if they started ART before 2015 and 42·0 years (41·7–42·3) left if they started ART after 2015. The corresponding estimates for men were 38·0 years (37·5–38·5) and 39·2 years (38·7–39·7). Interpretation: For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV. Funding: US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.

Background: Delay discounting has been found to be associated with numerous health-related outcomes, including risky sexual behaviour. To date, it is unclear whether delay discounting measured in different domains is associated within individuals. The goal of this study was to assess the concordance of monetary and sexual delay discounting in men who have sex with men. Methods: Participants completed an online survey, including the Monetary Choice Questionnaire and the Sexual Discounting Task. Linear regression models were used to assess the association between monetary and sexual discount rates. Results: Sexual discount rates did not predict monetary discount rates. There was a substantial amount of clustering of sexual discount rates, requiring sexual discounting data to be categorised. Conclusions: Monetary and sexual delay discounting are distinct processes that are not necessarily associated within individuals, and monetary delay discounting is not an appropriate proxy measure for sexual impulsivity. Data from the Sexual Discounting Task are typically rank-transformed for analysis. These data suggest that this might be an invalid method of analysis. Future studies should investigate the distribution of their data to determine if it is appropriate to analyse sexual discounting data as a continuous measure.

Data on the interaction between methicillin-resistant Staphylococcus aureus (MRSA) colonization and clinical infection are limited. During 2007-2008, we enrolled HIVinfected adults in Atlanta, Georgia, USA, in a prospective cohort study. Nares and groin swab specimens were cultured for S. aureus at enrollment and after 6 and 12 months. MRSA colonization was detected in 13%-15% of HIV-infected participants (n = 600, 98% male) at baseline, 6 months, and 12 months. MRSA colonization was detected in the nares only (41%), groin only (21%), and at both sites (38%). Over a median of 2.1 years of follow-up, 29 MRSA clinical infections occurred in 25 participants. In multivariate analysis, MRSA clinical infection was significantly associated with MRSA colonization of the groin (adjusted risk ratio 4.8) and a history of MRSA infection (adjusted risk ratio 3.1). MRSA prevention strategies that can effectively prevent or eliminate groin colonization are likely necessary to reduce clinical infections in this population.

After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts.Please see later in the article for the Editors' Summary.High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.

Background. Patterns of cause-specific mortality in individuals infected with human immunodeficiency virus type 1 (HIV-1) are changing dramatically in the era of antiretroviral therapy (ART). Methods. Sixteen cohorts from Europe and North America contributed data on adult patients followed from the start of ART. Procedures for coding causes of death were standardized. Estimated hazard ratios (HRs) were adjusted for transmission risk group, sex, age, year of ART initiation, baseline CD4 count, viral load, and AIDS status, before and after the first year of ART. Results. A total of 4237 of 65 121 (6.5%) patients died (median, 4.5 years follow-up). Rates of AIDS death decreased substantially with time since starting ART, but mortality from non-AIDS malignancy increased (rate ratio, 1.04 per year; 95% confidence interval [CI], 1.0-1.1). Higher mortality in men than women during the first year of ART was mostly due to non-AIDS malignancy and liver-related deaths. Associations with age were strongest for cardiovascular disease, heart/vascular, and malignancy deaths. Patients with presumed transmission through injection drug use had higher rates of all causes of death, particularly for liver-related causes (HRs compared with men who have sex with men: 18.1 [95% CI, 6.2-52.7] during the first year of ART and 9.1 [95% CI, 5.8-14.2] thereafter). There was a persistent role of CD4 count at baseline and at 12 months in predicting AIDS, non-AIDS infection, and non-AIDS malignancy deaths. Lack of viral suppression on ART was associated with AIDS, non-AIDS infection, and other causes of death. Conclusions. Better understanding of patterns of and risk factors for cause-specific mortality in the ART era can aid in development of appropriate care for HIV-infected individuals and inform guidelines for risk factor management.

Introduction: HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation. Methods: We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model. Results: The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL). Conclusions: In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.

Background. We investigated whether CD4:CD8 ratio and CD8 count were prognostic for all-cause, AIDS, and non-AIDS mortality in virologically suppressed patients with high CD4 count. Methods. We used data from 13 European and North American cohorts of human immunodeficiency virus-infected, antiretroviral therapy (ART)-naive adults who started ART during 1996-2010, who were followed from the date they had CD4 count ≥350 cells/μL and were virologically suppressed (baseline). We used stratified Cox models to estimate unadjusted and adjusted (for sex, people who inject drugs, ART initiation year, and baseline age, CD4 count, AIDS, duration of ART) all-cause and cause-specific mortality hazard ratios for tertiles of CD4:CD8 ratio (0-0.40, 0.41-0.64 [reference], >0.64) and CD8 count (0-760, 761-1138 [reference], >1138 cells/μL) and examined the shape of associations using cubic splines. Results. During 276 526 person-years, 1834 of 49 865 patients died (249 AIDS-related; 1076 non-AIDS-defining; 509 unknown/ unclassifiable deaths). There was little evidence that CD4:CD8 ratio was prognostic for all-cause mortality after adjustment for other factors: The adjusted hazard ratio (aHR) for lower vs middle tertile was 1.11 (95% confidence interval [CI], 1.00-1.25). The association of CD8 count with all-cause mortality was U-shaped: AHR for higher vs middle tertile was 1.13 (95% CI, 1.01-1.26). AIDSrelated mortality declined with increasing CD4:CD8 ratio and decreasing CD8 count. There was little evidence that CD4:CD8 ratio or CD8 count was prognostic for non-AIDS mortality. Conclusions. In this large cohort collaboration, the magnitude of adjusted associations of CD4:CD8 ratio or CD8 count with mortality was too small for them to be useful as independent prognostic markers in virally suppressed patients on ART.

Background:An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV-uninfected individuals more likely and whether restoration depends on gender, age, and other individual characteristics.Methods:We determined median and quartile reference values for CD4 and CD8 cell counts and their ratio using cross-sectional data from 2309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed-effects models.Results:When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first 2 years, median CD8 cell counts converged toward median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with <250 CD4 cells/mm 3 . Median CD4:CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm 3 .Discussion:Starting ART with a CD4 cell count of ≥500 cells/mm 3 makes reaching median reference CD4 cell counts more likely. However, median CD4:CD8 ratio trajectories remained below the median levels of HIV-negative individuals because of persisting high CD8 cell counts. To what extent these subnormal immunological responses affect specific clinical endpoints requires further investigation.