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Introduction: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation. Keywords: opportunistic infections; Pneumocystis jirovecii pneumonia; prophylaxis

Background. Low CD4+ T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4+ T-cell counts after triple-class virological failure.Methods. We included individuals from the COHERE database who started antiretroviral therapy from 1998 onward and who experienced triple-class virological failure. CD4+ T-cell counts obtained after triple-class virologic failure were analyzed using generalized estimating equations.Results. The analyses included 2424 individuals with a total of 23 922 CD4+ T-cell count measurements. In adjusted models (excluding current viral load and year), CD4+ T-cell counts were higher with regimens that included boosted protease inhibitors (increase, 22 cells/μL [95% confidence interval CI, 3.9-41]; P =. 017) or drugs from the new classes (increase, 39 cells/μL [95% CI, 15-62]; P =. 001), compared with nonnucleoside reverse-transcriptase inhibitor-based regimens. These associations disappeared when current viral load and/or calendar year were included. Compared with viral levels of 5.5 log10 copies/mL were associated with CD4+ T-cell count decreases of 51, 84, 137, and 186 cells/μL, respectively (P

Background Using data from a large European collaborative study, we aimed to identify the circumstances in which treated HIV-infected individuals will experience similar mortality rates to those of the general population. Methods Adults were eligible if they initiated combination anti-retroviral treatment (cART) between 1998 and 2008 and had one prior CD4 measurement within 6 months. Standardized mortality ratios (SMRs) and excess mortality rates compared with the general population were estimated using Poisson regression. Periods of follow-up were classified according to the current CD4 count. Results Of the 80 642 individuals, 70% were men, 16% were injecting drug users (IDUs), the median age was 37 years, median CD4 count 225/mm3 at cART initiation and median follow-up was 3.5 years. The overall mortality rate was 1.2/100 person-years (PY) (men: 1.3, women: 0.9), 4.2 times as high as that in the general population (SMR for men: 3.8, for women: 7.4). Among 35 316 individuals with a CD4 count ≥500/mm3, the mortality rate was 0.37/100 PY (SMR 1.5); mortality rates were similar to those of the general population in non-IDU men [SMR 0.9, 95% confidence interval (95% CI) 0.7-1.3] and, after 3 years, in women (SMR 1.1, 95% CI 0.7-1.7). Mortality rates in IDUs remained elevated, though a trend to decrease with longer durations with high CD4 count was seen. A prior AIDS diagnosis was associated with higher mortality. Conclusions Mortality patterns in most non-IDU HIV-infected individuals with high CD4 counts on cART are similar to those in the general population. The persistent role of a prior AIDS diagnosis underlines the importance of early diagnosis of HIV infection