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Background: It is unclear whether use of contemporary protease inhibitors pose a similar risk of chronic kidney disease (CKD) as use of older protease inhibitors.Methods: Participants in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study were followed up until the earliest occurrence of CKD, the last visit plus 6 months, or 1 February 2016. Adjusted Poisson regression was used to assess associations between CKD and the use of ritonavir-boosted atazanavir (ATV/r) or ritonavir-boosted darunavir (DRV/r).Results: The incidence of CKD (10.0/1000 person-years of follow-up; 95% confidence interval, 9.5-10.4/1000 person-years of follow-up) increased gradually with increasing exposure to ATV/r, but the relation was less clear for DRV/r. After adjustment, only exposure to ATV/r (adjusted incidence rate ratio, 1.4; 95% confidence interval, 1.2-1.6), but not exposure to DRV/r (1.0; .8-1.3), remained significantly associated with CKD.Conclusion: While DRV/r use was not significantly associated with CKD an increasing incidence with longer ATV/r use was confirmed. [ABSTRACT FROM AUTHOR]

Background Cancers are a major source of morbidity and mortality for human immunodeficiency virus (HIV)–infected persons, but the clinical benefits of smoking cessation are unknown. Methods Participants were followed from 1 January 2004 until first cancer diagnosis, death, or 1 February 2016. Smoking status was defined as ex-smoker, current smoker, and never smoker. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression, adjusting for demographic and clinical factors. Results In total 35442 persons from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study contributed 309803 person-years of follow-up. At baseline, 49% were current smokers, 21% were ex-smokers, and 30% had never smoked. Incidence of all cancers combined (n = 2183) was highest <1 year after smoking cessation compared to never smokers (aIRR, 1.66 [95% confidence interval {CI}, 1.37–2.02]) and not significantly different from never smokers 1–1.9 years after cessation. Lung cancer incidence (n = 271) was elevated <1 year after cessation (aIRR, 19.08 [95% CI, 8.10–44.95]) and remained 8-fold higher 5 years after smoking cessation (aIRR, 8.69 [95% CI, 3.40–22.18]). Incidence of other smoking-related cancers (n = 622) was elevated in the first year after cessation (aIRR, 2.06 [95% CI, 1.42–2.99]) and declined to a level similar to nonsmokers thereafter. Conclusions Lung cancer incidence in HIV-infected individuals remained elevated >5 years after smoking cessation. Deterring uptake of smoking and smoking cessation efforts should be prioritised to reduce future cancer risk. [ABSTRACT FROM AUTHOR]

Individuals with HIV are at a higher risk of stroke compared to uninfected populations. The role of HIV-related immunosuppression in stroke mechanism is uncertain. Our aim is to test the hypothesis that stroke mechanisms among HIV+ individuals vary according to preceding CD4 counts. We carried out a retrospective chart review of inpatient admissions for ICD-9 defined ischemic events (TIA or stroke) in HIV+ individuals from 2002 to 2016 at a tertiary care center. Stroke mechanisms were ascertained based on radiographic and clinical presentation, and adjudicated by the treating team and confirmed separately by a vascular neurologist. Vascular risk factors, use of antiretroviral drugs (ARVs), nadir CD4 and current CD4 counts (cells/mm3) were captured to build logistic regressions and generalized linear models to calculate the odds ratios (OR) and beta estimates with their respective 95% confidence intervals. We found that among 115 cases (median age 52, 64% men), stroke mechanisms were 22% due to large artery atherosclerosis (LAA), 17% small artery disease, 16% infectious, 8% cardioembolic, 21% cryptogenic, and 16% other etiologies. The median nadir CD4-count was 153 (IQR 22-274), and 312 (IQR 88-518) at the time of stroke, and 53% were on ARVs. LAA was more common with longer HIV infection (OR 1.1 per year, 1.0-1.2) and nadir CD4 counts <200 (OR 6.7, 1.4-31.9). Stroke due to LAA was associated with higher CD4 count the year prior to stroke (B = 0.009, P = 0.06 for the interaction) independent of CD4 nadir <200 (B = 1.88, P = 0.035). We concluded that in this sample, LAA was the most frequent stroke mechanism among HIV+ individuals with nadir CD4 < 200 but higher CD4 counts near the time of stroke. Determining the association between pre-stroke immune status and stroke mechanisms may allow a targeted approach to stroke prevention. [ABSTRACT FROM AUTHOR]

Background: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk.Methods: Data from the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different associations with NHL and HL were identified using marginal Cox models. All statistical tests were two-sided.Results: Among 41 420 people followed for 337 020 person-years, 392 developed NHL (incidence rate = 1.17/1000 person-years of follow-up [PYFU], 95% confidence interval [CI] = 1.06 to 1.30) and 149 developed HL (incidence rate = 0.44/1000 PYFU, 95% CI = 0.38 to 0.52). Higher risk of both NHL and HL was associated with lower current CD4 cell count (adjusted HR [aHR] of NHL for CD4 <100 vs > 599 cells/mm3 = 8.08, 95% CI = 5.63 to 11.61; HL = 4.58, 95% CI = 2.22 to 9.45), whereas higher current HIV viral load (aHR of NHL for HIV-VL >1000 vs < 50 copies/mL = 1.97, 95% CI = 1.50 to 2.59) and higher AUC of HIV-VL (aHR of NHL for highest vs lowest quintile = 2.91, 95% CI = 1.92 to 4.41) were associated with NHL only. Both current and AUC of HIV-VL were factors that had different associations with NHL and HL, where the hazard ratio for NHL was progressively higher than for HL with increasing HIV-VL category. Lower current CD4 cell count had a strong but similar association with both NHL and HL.Conclusions: CD4 depletion increased risk of both types of lymphomas while current and accumulated HIV-VL was associated with NHL only. This suggests that NHL development is related to both CD4 cell depletion and added immune dysfunction derived from ongoing HIV replication. This latter factor was not associated with HL risk. [ABSTRACT FROM AUTHOR]

Background: The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study has developed predictive risk scores for cardiovascular disease (CVD) and chronic kidney disease (CKD, defined as confirmed estimated glomerular filtration rate [eGFR] ≤ 60 ml/min/1.73 m2) events in HIV-positive people. We hypothesized that participants in D:A:D at high (>5%) predicted risk for both CVD and CKD would be at even greater risk for CVD and CKD events.Methods and Findings: We included all participants with complete risk factor (covariate) data, baseline eGFR > 60 ml/min/1.73 m2, and a confirmed (>3 months apart) eGFR < 60 ml/min/1.73 m2 thereafter to calculate CVD and CKD risk scores. We calculated CVD and CKD event rates by predicted 5-year CVD and CKD risk groups (≤1%, >1%-5%, >5%) and fitted Poisson models to assess whether CVD and CKD risk group effects were multiplicative. A total of 27,215 participants contributed 202,034 person-years of follow-up: 74% male, median (IQR) age 42 (36, 49) years, median (IQR) baseline year of follow-up 2005 (2004, 2008). D:A:D risk equations predicted 3,560 (13.1%) participants at high CVD risk, 4,996 (18.4%) participants at high CKD risk, and 1,585 (5.8%) participants at both high CKD and high CVD risk. CVD and CKD event rates by predicted risk group were multiplicative. Participants at high CVD risk had a 5.63-fold (95% CI 4.47, 7.09, p < 0.001) increase in CKD events compared to those at low risk; participants at high CKD risk had a 1.31-fold (95% CI 1.09, 1.56, p = 0.005) increase in CVD events compared to those at low risk. Participants' CVD and CKD risk groups had multiplicative predictive effects, with no evidence of an interaction (p = 0.329 and p = 0.291 for CKD and CVD, respectively). The main study limitation is the difference in the ascertainment of the clinically defined CVD endpoints and the laboratory-defined CKD endpoints.Conclusions: We found that people at high predicted risk for both CVD and CKD have substantially greater risks for both CVD and CKD events compared with those at low predicted risk for both outcomes, and compared to those at high predicted risk for only CVD or CKD events. This suggests that CVD and CKD risk in HIV-positive persons should be assessed together. The results further encourage clinicians to prioritise addressing modifiable risks for CVD and CKD in HIV-positive people. [ABSTRACT FROM AUTHOR]