Non-nucleoside reverse transcriptase inhibitors(Johnson & Johnson)

Drug resistance compromises the effectiveness of antiretroviral therapy (ART). Resistance testing prior to initiating therapy is recommended in guidelines in many high‐income countries, and it has been shown to improve outcomes after first‐line ART regimen failure. There is limited evidence on its role in treatment‐naïve individuals. We sought to investigate the association between resistance testing and viral suppression and mortality in people living with HIV initiating treatment in Ontario, Canada, where resistance testing became standard of care in 2014.

We conducted a retrospective cohort study from 2005 to 2018 using Ontario health administrative databases linked to the Ontario HIV Treatment Network (OHTN) Cohort Study (OCS). Eligible cohort participants were those who had complete data within the follow‐up time range. We used logistic regression to compare the odds of viral suppression (<200 copies/mL, at 6–18 months) and death between people living with HIV who had a record of resistance testing prior to treatment and those who did not. We adjusted for age, sex, year ART was started, race, sexual orientation, level of education, income, adherence, anchor drug, immigration status, injection drug use, viral load and baseline CD4 count.

Of 1806 eligible participants, 716 were analysed for death, of which 3.7% had died at the end of follow‐up. Six hundred and ninety‐nine (699) were analysed for viral suppression, of which 94.6% achieved viral suppression. Resistance testing prior to ART initiation had no significant association with viral suppression (odds ratio [OR] 1.13; 95% confidence interval [CI] 0.58–2.22) or death (OR 1.06 95% CI 0.49–2.28) in the covariate‐adjusted models. Viral suppression was more likely in older age and in people who started treatment with non‐nucleoside reverse transcriptase inhibitors compared to protease inhibitors, and in people with a higher baseline CD4 count. The odds of death were higher in individuals who were older.

Resistance testing was not associated with viral suppression and death. Outcomes were associated with clinical and demographic factors, notably regimen, baseline CD4 count and age.

Highly active antiretroviral therapy (HAART), consisting of three or more antiretroviral drugs, is recommended for patients with HIV infection. HAART effectively reduces HIV RNA levels, lowers the risk of opportunistic infections, and improves immune function and survival rates. However, it is also associated with an increased risk of liver injury in HIV‐infected individuals. This review aims to summarize the mechanisms underlying HAART‐induced liver injury. A comprehensive search was conducted in PubMed and EMBASE using keywords such as “Antiretroviral/ARV drugs and drug‐induced liver injury (DILI),” “HAART and DILI,” “Antiretroviral therapy and DILI,” and “HIV infection and DILI.” Relevant papers published before March 2024 were included. Experimental studies have demonstrated that zidovudine and efavirenz can cause structural alterations in mitochondria, impair the respiratory chain, generate free radicals, and deplete mitochondrial DNA, leading to oxidative and endoplasmic reticulum stress, as well as the accumulation of advanced glycation end products in liver tissue. Zidovudine disrupts lipid homeostasis by increasing fatty acid synthesis and reducing metabolism. Efavirenz and its metabolite, 8‐hydroxyefavirenz, induce hepatocellular death and activate proapoptotic markers through c‐Jun N‐terminal kinase signaling. Additionally, lamivudine has been shown to induce liver injury and oxidative stress in rats. Clinically, approximately 50% of HIV patients on HAART regimens containing non‐nucleoside reverse transcriptase inhibitors experience mild to moderate liver injury. HAART regimens that include efavirenz, lamivudine, and tenofovir impair glucose and lipid homeostasis in rats, highlighting the need for caution in HIV patients with fatty liver disease. Patients with viral hepatitis coinfection, those taking antitubercular drugs or cotrimoxazole, and those on nevirapine‐containing regimens are at particularly high risk. Regular monitoring of liver function is essential to prevent liver damage associated with HAART in HIV‐infected patients. While HAART significantly improves survival rates in HIV patients, it also poses a considerable risk of liver injury, necessitating careful monitoring and management.