Questioning risk compensation: pre-exposure prophylaxis (PrEP) and sexually transmitted infections among men who have sex with men, capital region of Denmark, 2019 to 2022.

BackgroundPre-exposure prophylaxis (PrEP) effectively prevents HIV, but its association with sexually transmitted infections (STIs) has raised concerns about risk compensation, potentially impacting the expansion of PrEP programmes.AimWe examined the relationship between PrEP and the incidence of chlamydia, gonorrhoea and syphilis.MethodsIn this prospective cohort study, we compared STI rates before and after PrEP initiation among users in the capital region of Denmark (2019-2022), calculating incidence rate ratios adjusted for age and testing frequency (aIRR). To pinpoint when increases began, we plotted weekly STI rates, adjusting the timeline to correspond with PrEP initiation.ResultsThe study included 1,326 PrEP users with a median age of 35 years. The STI incidence rate per 100,000 person-years rose from 35.3 before to 81.2 after PrEP start, with an aIRR of 1.35 (95% CI: 1.18-1.56). Notably, this increase preceded PrEP initiation by 10-20 weeks. Specific aIRR for chlamydia, gonorrhoea and syphilis were 1.23 (95% CI: 1.03-1.48), 1.24 (95% CI: 1.04-1.47) and 1.15 (95% CI: 0.76-1.72), respectively. In subanalyses for anatomical sites aIRR was 1.26 (95% CI: 1.01-1.56) for rectal chlamydia and 0.66 (95% CI: 0.45-0.96) for genital gonorrhoea.ConclusionWe found a 35% increase in STI incidence associated with PrEP use. It started before PrEP initiation, challenging the assumption that PrEP leads to risk compensation. Instead, the data suggest that individuals seek PrEP during periods of heightened sexual risk-taking. Consequently, PrEP programmes should include sexual health consultations, STI testing, treatment and prevention strategies to prevent HIV and improve sexual health.

Rapid Quantitative Point-Of-Care Diagnostic Test for Post COVID-19 Vaccination Antibody Monitoring.

Point-of-care (POC) quantification of antibody responses against SARS-CoV-2 spike protein can enable decentralized monitoring of immune responses after infection or vaccination. We evaluated a novel POC microfluidic cartridge-based device (ViroTrack Sero COVID-19 Total Ab) for quantitative detection of total antibodies against SARS-CoV-2 spike trimeric spike protein compared to standard laboratory chemiluminescence (CLIA)-based tests. Antibody responses of 101 individuals were measured on capillary blood, venous whole blood, plasma, and diluted plasma samples directly on the POC. Results were available within 7 min. As the reference, plasma samples were analyzed on DiaSorin LIAISON XL CLIA analyzer using LIAISON SARS-CoV-2 IgM, LIAISON SARS-CoV-2 S1/S2 IgG, and LIAISON SARS-CoV-2 TrimericS IgG assays. The Spearman rank's correlation coefficient between ViroTrack Sero COVID-19 Total Ab and LIAISON SARS-CoV-2 S1/S2 IgG and LIAISON SARS-CoV-2 TrimericS IgG assays was found to be 0.83 and 0.89, respectively. ViroTrack Sero COVID-19 Total Ab showed high correlation between the different matrixes. Agreement for determination of samples of >230 binding antibody units (BAU)/mL on POC and CLIA methods is estimated to be around 90%. ViroTrack Sero Covid Total Ab is a rapid and simple-to-use POC test with high sensitivity and correlation of numerical results expressed in BAU/mL compared to those of a commercial CLIA assay. IMPORTANCE Serological testing is an important diagnostic support tool in the fight against COVID-19. So far, serological testing has been performed on either lateral flow assays, which perform only qualitatively and can be difficult for the individual to read, or standard laboratory assays, which are time- and resource-consuming. The purpose of the study was to evaluate the performance of a new POC microfluidic cartridge-based device based on immunomagnetic agglutination assay that can provide an accurate numerical quantification of the total antibodies within only 7 min from a single drop of capillary blood. We demonstrated a high level of correlation between the POC and the two CLIA laboratory-based immunoassays from Diasorin, thus allowing a potentially wider use of quantitative serology tests in the COVID-19 pandemic.

Evaluation of commercially available immuno-magnetic agglutination in comparison to enzyme-linked immunosorbent assays for rapid point-of-care diagnostics of COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Fast, accurate, and simple blood-based assays for quantification of anti-SARS-CoV-2 antibodies are urgently needed to identify infected individuals and keep track of the spread of disease. METHODS: The study included 33 plasma samples from 20 individuals with confirmed COVID-19 by real-time reverse-transcriptase polymerase chain reaction and 40 non-COVID-19 plasma samples. Anti-SARS-CoV-2 immunoglobulin M (IgM)/immunoglobulin A (IgA) or immunoglobulin G (IgG) antibodies were detected by a microfluidic quantitative immunomagnetic assay (IMA) (ViroTrack Sero COVID IgM + IgA/IgG Ab, Blusense Diagnostics) and compared to an enzyme-linked immunosorbent assay (ELISA) (EuroImmun Medizinische Labordiagnostika). RESULTS: Of the 33 plasma samples from the COVID-19 patients, 28 were positive for IgA/IgM or IgG by IMA and 29 samples were positive by ELISA. Sensitivity for only one sample per patient was 68% for IgA + IgM and 75% IgG by IMA and 80% by ELISA. For samples collected 14 days after symptom onset, the sensitivity of both IMA and ELISA was around 91%. The specificity of the IMA reached 100% compared to 95% for ELISA IgA and 97.5% for ELISA IgG. CONCLUSION: IMA for COVID-19 is a rapid simple-to-use point-of-care test with sensitivity and specificity similar to a commercial ELISA.

Similar long-term survival of consecutive in-hospital and out-of-hospital cardiac arrest patients treated with targeted temperature management.

OBJECTIVE: The long-term survival of in-hospital cardiac arrest (IHCA) patients treated with targeted temperature management (TTM) is poorly described. The aim of this study was to compare the outcomes of consecutive IHCA with out-of-hospital cardiac arrest (OHCA) patients treated with TTM. DESIGN SETTING AND PATIENTS: Retrospectively collected data on all consecutive adult patients treated with TTM at a university tertiary heart center between 2005 and 2011 were analyzed. MEASUREMENTS: Primary endpoints were survival to hospital discharge and long-term survival. Secondary endpoint was neurological outcome assessed using the Pittsburgh cerebral performance category (CPC). RESULTS: A total of 282 patients were included in this study; 233 (83%) OHCA and 49 (17%) IHCA. The IHCA group presented more often with asystole, received bystander cardiopulmonary resuscitation (CPR) in all cases, and had shorter time to return of spontaneous circulation (ROSC). Survival to hospital discharge was 54% for OHCA and 53% for IHCA (adjusted odds ratio 0.98 [95% confidence interval {CI}; 0.43-2.24]). Age ≤60 years, bystander CPR, time to ROSC ≤10 min, and shockable rhythm at presentation were associated with survival to hospital discharge. Good neurologic outcome among survivors was achieved by 86% of OHCA and 92% of IHCA (P=0.83). After a median follow-up time of >5 years, 83% of OHCA and 77% of IHCA were alive (adjusted hazard ratio [HR] 1.51 [95% CI; 0.59-3.91]). Age ≤60 years was the only factor associated with long-term survival (adjusted HR 2.73 [95% CI; 1.36-5.52]). CONCLUSION: There was no difference in short- and long-term survival and no difference in neurologic outcome to hospital discharge between IHCA and OHCA patients treated with TTM despite higher frequency of asystole in IHCA.

Effectiveness of antiretroviral therapy in individuals who for economic reasons were switched from a once-daily single-tablet regimen to a triple-tablet regimen.

BACKGROUND: To assess the impact on virological outcomes of a switch from branded single-tablet regimen (STR) including tenofovir, efavirenz, and emtricitabine (STR-TEE) to generic triple-tablet regimen (TTR), including tenofovir, efavirenz, and lamivudine (TTR-TEL), which was implemented on April 1, 2011 to obtain economic savings. METHODS AND FINDINGS: From the Capital Region of Denmark (covering two-thirds of the Danish HIV patients), we included combination antiretroviral therapy (cART)-naive patients who administered STR-TEE from April 1, 2010 to March 31, 2011 (n = 111) or TTR-TEL from April 1, 2011 to March 31, 2012 (n = 56) and cART-experienced HIV patients who were on STR-TEE from April 1, 2010 (n = 356) or were switched from STR-TEE to TTR-TEL after April 1, 2011 (n = 512). We estimated the fraction with detectable HIV-RNA, development of the 184V/I resistance mutations, and time to switch of cART. Approximately 96.2% of cART-experienced patients on STR-TEE were shifted to TTR-TEL after April 1, 2011. For the naive STR-TEE and TTR-TEL patients, the fractions with detectable HIV-RNA at week 48 were 7.0% and 8.3% and for the cART experienced 4.0% and 4.4%, respectively. The 184V/I resistance mutation was detected in 1 cART-experienced patient on TTR-TEL with virological failure. The risk of switch to a new cART regimen was slightly increased in the cART-experienced population (difference in 1-year risk: 1.5%; 95% confidence interval: -2.4% to 5.4%). CONCLUSIONS: In settings comparable with the Danish health care system, the estimated economic savings from a switch from STR-TEE to TTR-TEL can be realized with negligible short-term risk of adverse outcomes.

Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery.

BACKGROUND: Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. METHODS: We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. RESULTS: Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death. CONCLUSIONS: Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.

Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population.

BACKGROUND: Due to the success of antiretroviral therapy (ART), it is relevant to ask whether death rates in optimally treated HIV are higher than the general population. The objective was to compare mortality rates in well controlled HIV-infected adults in the SMART and ESPRIT clinical trials with the general population. METHODS: Non-IDUs aged 20-70 years from the continuous ART control arms of ESPRIT and SMART were included if the person had both low HIV plasma viral loads (≤400 copies/ml SMART, ≤500 copies/ml ESPRIT) and high CD4(+) T-cell counts (≥350 cells/µl) at any time in the past 6 months. Standardized mortality ratios (SMRs) were calculated by comparing death rates with the Human Mortality Database. RESULTS: Three thousand, two hundred and eighty individuals [665 (20%) women], median age 43 years, contributed 12,357 person-years of follow-up. Sixty-two deaths occurred during follow up. Commonest cause of death was cardiovascular disease (CVD) or sudden death (19, 31%), followed by non-AIDS malignancy (12, 19%). Only two deaths (3%) were AIDS-related. Mortality rate was increased compared with the general population with a CD4(+) cell count between 350 and 499 cells/µl [SMR 1.77, 95% confidence interval (CI) 1.17-2.55]. No evidence for increased mortality was seen with CD4(+) cell counts greater than 500 cells/µl (SMR 1.00, 95% CI 0.69-1.40). CONCLUSION: In HIV-infected individuals on ART, with a recent undetectable viral load, who maintained or had recovery of CD4(+) cell counts to at least 500 cells/µl, we identified no evidence for a raised risk of death compared with the general population.

Renal function and incidence of chronic kidney disease in HIV patients: a Danish cohort study.

BACKGROUND: Impaired renal function is of major concern in human immunodeficiency virus (HIV)-infected patients. METHODS: We used a mixed effects linear regression model to determine estimated glomerular filtration rates (eGFRs) in a population-based cohort of incident Danish HIV patients and stratified on baseline eGFR (eGFR(B)) < 90 and ≥ 90 ml/min per 1.73 m(2). Incidence rate ratios (IRRs) for chronic kidney disease (CKD) - 2 consecutive eGFR values < 60 ml/min per 1.73 m(2) measured > 3 months apart - were estimated (time-updated Cox-regression model). RESULTS: The effect of time with HIV on eGFR was small in both strata (- 0.09 (95% confidence interval (CI) - 0.27, 0.09) and - 0.46 (95% CI - 0.64, - 0.27) ml/min per 1.73 m(2) per y). Treatment with tenofovir and indinavir was associated with lower eGFR in both strata: tenofovir - 2.00 (95% CI - 3.45, - 0.56) and - 1.94 (95% CI - 3.43, - 0.44) ml/min per 1.73 m(2) and indinavir - 2.14 (95% CI - 3.63, - 0.64) and - 3.29 (95% CI - 5.25, - 1.32) ml/min per 1.73 m(2). Nevirapine, atazanavir, and the combination of tenofovir and atazanavir were associated with lower eGFR in patients with eGFR(B) < 90 ml/min per 1.73 m(2). Highly active antiretroviral therapy (HAART) and exposure to tenofovir and atazanavir in combination were associated with CKD in patients with eGFR(B) < 90 ml/min per 1.73 m(2) (adjusted IRRs 6.08 (95% CI 2.76-13.41) and 26.75 (95% CI 9.54-75.05)). CONCLUSION: Tenofovir and indinavir reduce eGFR, while time with HIV only has a modest effect on this parameter. Low eGFR(B) is associated with an increased risk of CKD, especially when receiving HAART regimens containing the combination tenofovir/atazanavir.

Late presenters, repeated testing, and missed opportunities in a Danish nationwide HIV cohort.

BACKGROUND: We aimed to estimate the incidence and predictors of late presentation among human immunodeficiency virus (HIV)-infected individuals in Denmark. METHODS: Incidence rates (IR) of presentation with advanced HIV (CD4 < 200 cells/µl and/or acquired immune deficiency syndrome (AIDS)) and late presentation (CD4 < 350 cells/µl and/or AIDS) were calculated per 100,000 population aged 16-60 y. Mortality rate ratios (MRR) were estimated using Poisson regression analysis. RESULTS: Three thousand and twenty-seven individuals were diagnosed with HIV in 1995-2009; 34.7% presented with advanced HIV and 51.2% were late presenters. The IR of HIV was stable (6.2/100,000 population), but IR of presentation with advanced HIV declined during the study period from 2.2 (95% confidence interval (CI) 1.8-2.8) to 1.1 (95% CI 0.8-1.5). Age >50 y, heterosexuals of non-Danish origin, 'other' route of transmission, and diagnosis before 2002 were associated with an increased risk of presenting with advanced HIV, whereas a negative HIV test prior to diagnosis was associated with a significantly reduced risk. A total of 414 individuals (40.0%) had attended a hospital 1-3 y before presenting with advanced HIV. After 2002 the proportion of men who have sex with men with a negative HIV test prior to diagnosis increased (incidence rate ratio (IRR) 1.3, 95% CI 1.1-1.6), coinciding with a reduction in IR of presentation with advanced HIV. Mortality rates were increased the first 2 y following presentation with advanced HIV (MRR 5.9, 95% CI 3.6-9.4 and MRR 2.5, 95% CI 1.4-4.1, respectively). CONCLUSION: In a setting with a low HIV prevalence, the rate of presentation with advanced HIV can potentially be reduced by repeated HIV testing of individuals with a continuous high risk of transmission and by adhering to guidelines for targeted HIV testing.

Retention in a public healthcare system with free access to treatment: a Danish nationwide HIV cohort study.

OBJECTIVE: We aimed to assess retention of HIV-infected individuals in the Danish healthcare system over a 15-year period. METHODS: Loss to follow-up (LTFU) was defined as 365 days without contact to the HIV care system. Data were obtained from the nationwide Danish HIV Cohort study, The Danish National Hospital Registry and The Danish Civil Registration System. Incidence rates, risk factors for LTFU and return to care and mortality rate ratios (MRRs) were estimated using Poisson regression analyses. RESULTS: We included 4745 HIV patients who were followed for 36,692 person-years. Patients were retained in care 95.0% of person-years under observation, increasing to 98.1% after initiation of highly active antiretroviral treatment (HAART). The overall incidence rate/100 person-years for first episode of LTFU was 2.6 [95% confidence interval (CI) 2.5-2.8] and was significantly lower after initiation of HAART [1.2 (95% CI 1.0-1.3)]. Five years after LTFU the probability of return to care was 0.87 (95% CI 0.84-0.90). The risk of death was significantly increased after LTFU [MRR 1.9 (95% CI 1.6-2.6)] and 6 months or less after return to care [MRR 10.9 (95% CI 5.9-19.9)]. CONCLUSION: Retention in care of Danish HIV patients is high, especially after initiation of HAART. Absence from HIV care is associated with increased mortality. We conclude that high rates of retention can be achieved in a healthcare system with free access to treatment and is associated with a favorable outcome.

Head and neck cancer in HIV patients and their parents: a Danish cohort study.

BACKGROUND: The mechanism for the increased risk of head and neck cancer (HNC) observed in HIV patients is controversial. We hypothesized that family-related risk factors increase the risk of HNC why we estimated the risk of this type of cancer in both HIV patients and their parents. METHODS: We estimated the cumulative incidence and incidence rate ratios (IRRs) of HNC in 1) a population of all Danish HIV patients identified from the Danish HIV Cohort Study (n = 5053) and a cohort of population controls matched on age and gender (n = 50,530) (study period; 1995-2009) and 2) the parents of HIV patients and population controls (study period 1978-2009). To assess the possible impact of human papilloma virus (HPV)-associated cancers, the sites of squamous cell HNCs were categorized as HPV related, potentially HPV related, and potentially HPV unrelated. RESULTS: Seventeen (0.3%) HIV patients vs 80 (0.2%) population controls were diagnosed with HNC cancer in the observation period. HIV patients had an increased risk of HNC (IRR 3.05 [95% CI 1.81-5.15]). The IRR was considerably increased in HIV patients older than 50 years (adjusted IRR; 4.58 [95% CI 2.24-9.35]), diagnosed after 1995 (adjusted IRR 6.31 [95% CI 2.82-14.08]), previous or current smoker (adjusted IRR 4.51 [95% CI 2.47-8.23]), with baseline CD4 count 350 cells/µL (adjusted IRR; 3.89 [95% CI 1.95-7.78]), and men heterosexually infected with HIV (adjusted IRR 5.54 [95% CI 1.96-15.66]). Fifteen (83%) of the HIV patients diagnosed with HNC were current or former smokers. The IRR of squamous cell HNC in HIV patients was high at HPV-relate sites, potentially HPV-related sites, and potentially HPV-unrelated sites. Both fathers and mothers of HIV patients had an increased risk of HNC (adjusted IRR for fathers 1.78 [95% CI 1.28-2.48], adjusted IRR for mothers 2.07 [95% CI 1.05-4.09]). CONCLUSION: HIV appears to be a marker of behavioral or family-related risk factors that affect the incidence of HNC in HIV patients.

Risk of cerebrovascular events in persons with and without HIV: a Danish nationwide population-based cohort study.

OBJECTIVE: To assess the risk of cerebrovascular events (CVEs) in HIV-infected individuals and evaluate the impact of proven risk factors, injection drug abuse (IDU), immunodeficiency, HAART and family-related risk factors. DESIGN: Nationwide, population-based cohort study. METHODS: The study population included all Danish HIV-infected individuals, a population-based comparison cohort and parents of both cohorts - all with no prior cerebral comorbidity. We computed incidence rate ratios (IRRs) of overall CVEs and CVEs with and without proven risk factors, stratifying the analyses on IDU. Impact of immunodeficiency, HAART, protease inhibitors, indinavir, didanosin, tenofovir and abacavir on risk of CVEs was analyzed using time-dependent Cox regression analyses. RESULTS: HIV-infected individuals had an increased risk of CVEs compared with the comparison cohorts [(non-IDU HIV adjusted IRR 1.60; 95% confidence interval [CI] 1.32-1.94), (IDU HIV adjusted IRR 3.94; 95% CI 2.16-7.16)]. The risk was increased with and without proven risk factors. A CD4 cell count of 200 cells/µl or less before the start of HAART and exposure to abacavir increased the risk of CVE [(adjusted IRR 2.26; 95% CI 1.05-4.86) and (adjusted IRR 1.66; 95% CI 1.03-2.68)]. Protease inhibitors, indinavir, didanosin, tenofovir and HAART in general had no impact. Risk of CVEs was only increased in the parents of IDU HIV-infected individuals. CONCLUSION: HIV-infected individuals have an increased risk of CVEs with and without proven risk factors. The risk is associated with IDU, low CD4 cell count and exposure to abacavir, but not with HAART. An association with family-related risk factors seems vague except for parents of IDU individuals.

Lung cancer in HIV patients and their parents: a Danish cohort study.

BACKGROUND: HIV patients are known to be at increased risk of lung cancer but the risk factors behind this are unclear. METHODS: We estimated the cumulative incidence and relative risk of lung cancer in 1) a population of all Danish HIV patients identified from the Danish HIV Cohort Study (n = 5,053) and a cohort of population controls matched on age and gender (n = 50,530) (study period; 1995 - 2009) and 2) their parents (study period; 1969 - 2009). Mortality and relative risk of death after a diagnosis of lung cancer was estimated in both populations. RESULTS: 29 (0.6%) HIV patients vs. 183 (0.4%) population controls were diagnosed with lung cancer in the observation period. HIV patients had an increased risk of lung cancer (adjusted incidence rate ratio (IRR); 2.38 (95% CI; 1.61 - 3.53)). The IRR was considerably increased in HIV patients who were smokers or former smokers (adjusted IRR; 4.06 (95% CI; 2.66 - 6.21)), male HIV patients with heterosexual route of infection (adjusted IRR; 4.19 (2.20 - 7.96)) and HIV patients with immunosuppression (adjusted IRR; 3.25 (2.01 - 5.24)). Both fathers and mothers of HIV patients had an increased risk of lung cancer (adjusted IRR for fathers; 1.31 (95% CI: 1.09 - 1.58), adjusted IRR for mothers 1.35 (95% CI: 1.07 - 1.70)). Mortality after lung cancer diagnose was increased in HIV patients (adjusted mortality rate ratio 2.33 (95%CI; 1.51 - 3.61), but not in the parents. All HIV patients diagnosed with lung cancer were smokers or former smokers. CONCLUSION: The risk was especially increased in HIV patients who were smokers or former smokers, heterosexually infected men or immunosuppressed. HIV appears to be a marker of behavioural or family related risk factors that affect the incidence of lung cancer in HIV patients.

Incidence, risk factors and mortality of tuberculosis in Danish HIV patients 1995-2007.

BACKGROUND: Human Immunodeficiency Virus (HIV) infection predisposes to tuberculosis (TB). We described incidence, risk factors and prognosis of TB in HIV-1 infected patients during pre (1995-1996), early (1997-1999), and late Highly Active Antiretroviral Therapy (HAART) (2000-2007) periods. METHODS: We included patients from a population-based, multicenter, nationwide cohort. We calculated incidence rates (IRs) and mortality rates (MRs). Cox's regression analysis was used to estimate risk factors for TB infection with HAART initiation included as time updated variable. Kaplan-Meier was used to estimate mortality after TB. RESULTS: Among 2,668 patients identified, 120 patients developed TB during the follow-up period. The overall IR was 8.2 cases of TB/1,000 person-years of follow-up (PYR). IRs decreased during the pre-, early and late-HAART periods (37.1/1000 PYR, 12.9/1000 PYR and 6.5/1000 PYR respectively). African and Asian origin, low CD4 cell count and heterosexual and injection drug user route of HIV transmission were risk factors for TB and start of HAART reduced the risk substantially. The overall MR in TB patients was 34.4 deaths per 1,000 PYR (95% Confidence Interval: 22.0-54.0) and was highest in the first two years after the diagnosis of TB. CONCLUSIONS: Incidence of TB still associated with conventional risk factors as country of birth, low CD4 count and route of HIV infection while HAART reduces the risk substantially. The mortality in this patient population is high in the first two years after TB diagnosis.

Long-term mortality in HIV patients virally suppressed for more than three years with incomplete CD4 recovery: a cohort study.

BACKGROUND: The mortality in patients with persistent low CD4 count despite several years of HAART with sustained viral suppression is poorly documented. We aimed to identify predictors for inadequate CD4 cell recovery and estimate mortality in patients with low CD4 count but otherwise successful HAART. METHOD: In a nationwide cohort of HIV patients we identified all individuals who started HAART before 1 January 2005 with CD4 cell count ≤ 200 cells/µL and experienced three years with sustained viral suppression. Patients were categorized according to CD4 cell count after the three years suppressed period (≤ 200 cells/µL; immunological non-responders (INRs), >200 cells/µL; immunological responders (IRs)). We used logistic regression and Kaplan-Meier analysis to estimated risk factors and mortality for INRs compared to IRs. RESULTS: We identified 55 INRs and 236 IRs. In adjusted analysis age > 40 years and > one year from first CD4 cell count ≤ 200 cells/µL to start of the virologically suppressed period were associated with increased risk of INR. INRs had substantially higher mortality compared to IRs. The excess mortality was mainly seen in the INR group with > one year of immunological suppression prior to viral suppression and injection drug users (IDUs). CONCLUSION: Age and prolonged periods of immune deficiency prior to successful HAART are risk factors for incomplete CD4 cell recovery. INRs have substantially increased long-term mortality mainly associated with prolonged immunological suppression prior to viral suppression and IDU.

Clinical, virological and immunological responses in Danish HIV patients receiving raltegravir as part of a salvage regimen.

BACKGROUND: Raltegravir is the first integrase inhibitor approved for treatment of HIV-infected patients harboring multiresistant viruses. METHODS: From a Danish population-based nationwide cohort of HIV patients we identified the individuals who initiated a salvage regimen including raltegravir and a matched cohort of HIV-infected patients initiating HAART for the first time. We compared these two cohorts for virological suppression, gain in CD4 count, and time to first change of initial regimen. RESULTS: We identified 32 raltegravir patients and 64 HIV patients who initiated HAART for the first time in the period 1 January 2006 to 1 July 2009. The virological and immunological responses in the raltegravir patients were comparable to those seen in the control cohort. No patients in the two cohorts died and no patients terminated raltegravir treatment in the observation period. Time to first change of initial regimen was considerably shorter for HAART-naïve patients. CONCLUSION: We conclude that salvage regimens including raltegravir have high effectiveness in the everyday clinical setting. The effectiveness of the regimens is comparable to that observed for patients initiating HAART for the first time. The risk of change in the salvage regimens after initiation of raltegravir is low.