CD4/CD8 Ratio Outcome According to the Class of the Third Active Drug in Antiretroviral Therapy Regimens: Results From the Quebec Human Immunodeficiency Virus Cohort Study.

BACKGROUND: The impact of different therapeutic classes of drugs in antiretroviral therapy (ART) regimens on the CD4/CD8 ratio is not well documented in people treated for HIV. The objective of this study was to analyze the long-term effect of exposure to integrase strand transfer inhibitor (INSTI) on CD4/CD8 ratio compared with nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) among ART-treated persons with HIV (PWH). METHODS: Data from the Quebec HIV Cohort collected from 31 August 2017 were used. Our analysis included all patients in the cohort who received a first or subsequent ART regimen composed of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and a third active drug of a different class (NNRTI, PI, or INSTI) for at least 16 weeks. Marginal structural Cox models were constructed to estimate the effect of different therapeutic classes on the CD4/CD8 ratio outcome. RESULTS: Among the 3907 eligible patients, 972 (24.9%), 1996 (51.1%), and 939 (24.0%) were exposed to an ART regimen whose third active agent was an NNRTI, PI, or INSTI, respectively. The total follow-up time was 13 640.24 person-years. The weighted hazard ratio for the association between the third active class and CD4/CD8 ratio ≥1 was .56 (95% confidence interval [CI]: .48-.65) for patients exposed to NNRTI + 2 NRTIs and .41 (95% CI: .35-.47) for those exposed to PI + 2 NRTIs, compared with those exposed INSTI + 2 NRTIs. CONCLUSIONS: For people treated for HIV, INSTI-based ART appears to be associated with a higher CD4/CD8 ratio than NNRTI and PI-based ART.

Treatment Switch to Dolutegravir With 2 Nucleoside Reverse-Transcriptase Inhibitors (NRTI) in Comparison to Continuation With Protease Inhibitor/Ritonavir Among Patients With Human Immunodeficiency Virus at Risk for Prior NRTI Resistance: A Cohort Analysis of Real-World Data.

BACKGROUND: Switching antiretroviral regimens when human immunodeficiency virus (HIV) viremia is controlled for a new regimen is challenging when there is the potential for prior nucleoside reverse-transcriptase inhibitor (NRTI) resistance. The objective was to study virologic outcomes after switching to dolutegravir compared with remaining on a boosted protease inhibitor (protease inhibitor/ritonavir [PI/r]) regimen in people with HIV (PWH) with prior documented virologic failure and/or exposure to mono/dual NRTIs. METHODS: We used the Quebec HIV Cohort including 10 219 PWH whose data were collected at 4 sites in Montreal, Canada. We included all PWH with documented virologic failure or exposure to mono/dual NRTI therapy who were virologically suppressed on a PI/r-based regimen for at least 6 months on or after January 1, 2014 (n = 532). A marginal structural Cox model analysis was used to estimate the effect of the switch to dolutegravir on virologic outcome compared with remaining on PI/r. The outcome was defined as 2 consecutive viral loads (VLs) >50 copies/mL or 1 VL >50 copies/mL if it occurred at the last VL available. RESULTS: Among 532 eligible participants, 216 (40.6%) had their regimen switched to dolutegravir with 2 NRTIs, whereas 316 (59.4%) remained on the PI/r with 2 NRTIs. The weighted hazard ratio for the effect of dolutegravir switch on virologic failure compared with patients whose regimen remained on PI/r was 0.57 (95% confidence interval, 0.21-1.52). CONCLUSIONS: We did not find evidence of an increased risk for virologic failure after switching to dolutegravir from PI/r among patients with previous virologic failure or prior exposure to mono/dual NRTI.

Impact of previous HIV resistance and virologic failures on virologic outcome following a switch to dolutegravir with 2 NRTIs among people living with HIV.

There is uncertainty regarding the potential virologic outcome associated with a change in antiretroviral therapy (ARV) among PLHIV who had previous documented virologic failure or who have been exposure to mono/dual nucleoside reverse transcriptase inhibitors (NRTI) therapy. The objective was to measure the potential impact of exposure to previous virologic failure or mono/dual NRTI regimen on virologic outcome of PLHIV following a switch to dolutegravir with 2 NRTIs from a viremia suppressive ARV therapy.Data from the Quebec HIV Cohort including 10219 PLHIV were collected through routine clinical care at 4 clinical sites in Montreal, Canada. This study includes patients whose ARV therapy was switched to dolutegravir with 2 NRTIs since 2013 with undetectable viral load for ≥6 months before switch. The association between exposure and post-switch virologic outcome was measured by marginal hazard ratio estimated using the Inverse probability weighting Cox model.Among the 1199 eligible PLHIV, 478 (39.9%) previously experienced at least one virologic failure or were exposed to mono/dual therapy before dolutegravir switch. Post-switch virologic failure after 30 months occurred in 4.1% (95% CI 2.1-7.9) of exposed compared to 4.1% (95% CI 2.3-7.4) in unexposed participants. The adjusted hazard ratio for the association between exposure and post-switch virologic failure was 0.84 (95% CI 0.35-2.01).Our findings suggest that switch to dolutegravir with 2 NRTIs from a suppressive therapy is a safe option for PLHIV with documented virologic failure and/or previous exposure to mono/dual NRTI therapy.

Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis.

BACKGROUND & AIMS: Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear. METHODS: The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP >292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM] >7.1kPa), or transition to cirrhosis (LSM >12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression. RESULTS: A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection. CONCLUSION: HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to frequent metabolic disorders and the long-term effects of antiretroviral therapy. However, due to the invasiveness of liver biopsy, the traditional method of diagnosing fatty liver, there are few data regarding its frequency in people living with HIV. In this study, we used a non-invasive diagnostic tool to analyze the epidemiology of fatty liver in 726 HIV+ patients. We found that fatty liver affects over one-third of people living with HIV. When followed over time, we found that HIV+ patients without HCV co-infection develop fatty liver more frequently than those co-infected with HCV.

Nonalcoholic fatty liver disease diagnosed by transient elastography with controlled attenuation parameter in unselected HIV monoinfected patients.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. HIV-infected persons without viral hepatitis are at increased risk of NAFLD. Nevertheless, data on NAFLD in HIV monoinfection are scarce. DESIGN/METHODS: We prospectively investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography and associated controlled attenuation parameter (CAP) in unselected HIV-infected adults without significant alcohol intake or viral hepatitis coinfection. NAFLD was defined as CAP at least 238 dB/m. Significant liver fibrosis and cirrhosis were defined as transient elastography measurement at least 7.1 and 13 kPa, respectively. Predictors of NAFLD and significant liver fibrosis were determined using logistic regression analysis. RESULTS: A total of 300 consecutive patients (mean age 50 years, 77% men; mean CD4 cell count 570 cells/µl, 90% on antiretrovirals) were included as a part of a routine screening program. Transient elastography with CAP identified NAFLD and significant liver fibrosis in 48 and 15% of cases, respectively. NAFLD was independently associated with BMI more than 25 kg/m [adjusted odds ratio (aOR) 4.86, 95% confidence interval (CI) 2.55-9.26] and elevated alanine aminotransferase (ALT) (aOR 3.17, 95% CI 1.43-7.03). Independent predictors of significant liver fibrosis were diabetes (aOR 5.84, 95% CI 1.91-17.85), elevated ALT (aOR 3.30, 95% CI 1.27-8.59) and current use of protease inhibitors (aOR 3.96, 95% CI 1.64-9.54). CONCLUSION: NAFLD and significant liver fibrosis diagnosed by transient elastography with CAP are major comorbidities in unselected HIV monoinfected persons on antiretroviral therapy, particularly if metabolic conditions and elevated ALT coexist. Noninvasive screening for NAFLD should be implemented in this population to establish early interventions and prevent complications.

Incidence and predictors of hepatic steatosis and fibrosis by serum biomarkers in a large cohort of human immunodeficiency virus mono-infected patients.

Background. Longitudinal data on liver disease in human immunodeficiency virus (HIV) mono-infection are scarce. We used noninvasive serum biomarkers to study incidence and predictors of hepatic steatosis and fibrosis. Methods. Hepatic steatosis was diagnosed by hepatic steatosis index ≥36. Advanced liver fibrosis was diagnosed by fibrosis-4 index >3.25. Kaplan-Meier analysis was used to estimate incidences. Cox regression analysis was used to explore predictors of hepatic steatosis and fibrosis development. Results. In this retrospective observational study, 796 consecutive HIV mono-infected patients were observed for a median of 4.9 (interquartile range, 2.2-6.4) years. Incidence of hepatic steatosis was 6.9 of 100 per person-years (PY) (95% confidence interval [CI], 5.9-7.9). Incidence of advanced liver fibrosis was 0.9 of 100 PY (95% CI, 0.6-1.3). Development of hepatic steatosis was predicted by black ethnicity (adjusted hazard ratio [aHR] = 2.18; 95% CI, 1.58-3; P < .001) and lower albumin (aHR = 0.94; 95% CI, 0.91-0.97; P < .001). Development of advanced liver fibrosis was predicted by higher glucose (aHR = 1.22; 95% CI, 1.2-1.3; P < .001) and lower albumin (aHR = 0.89; 95% CI, 0.84-0.93; P < .001). Conclusions. Incident hepatic steatosis is frequent in HIV mono-infected patients, particularly in those of black ethnicity. These patients can also develop advanced liver fibrosis. Identification of at-risk individuals can help early initiation of hepatological monitoring and interventions, such as targeting euglycemia.