Burden of Disease in PWH Harboring a Multidrug-Resistant Virus: Data From the PRESTIGIO Registry

Abstract

Background: Currently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population.

Methods: This was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Cox regression models evaluated factors associated with the risk of new clinical events/death.

Results: Among 148 PWH followed for a median (interquartile range) of 47 (32-84) months after 4DR evidence, 38 PWH had 62 new events or died from any cause (incidence rate, 9.12/100 person-years of follow-up; 95% CI = 6.85-11.39): 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADEs, 32 NADEs; 20 of the 38 NADEs (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95% CI, 3%-13%), and that of ≥1 event or death was 22% (95% CI, 16%-31%). A higher risk of new clinical events/death was more likely in PWH with previous clinical events (adjusted hazard ratio [aHR], 2.67; 95% CI, 1.07-6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR, 0.82; 95% CI, 0.65-1.02).

Conclusions: PWH harboring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio.

Keywords: 4-class drug resistance; AIDS-defining event; cancer; death; non-AIDS-defining event.

Figure 1.

Time to death from any cause. Twelve people with HIV died (incidence rate, 1.76/100 person-years of follow-up; 95% CI, 0.91–2.90): 6 AIDS-related deaths (1 wasting syndrome, 1 non-Hodgkin lymphoma [Burkitt], 1 tuberculous meningoencephalitis, 1 Pneumocystis jirovecii¸ 1 mycobacteriosis, 1 extrapulmonary Mycobacterium tuberculosis) and 6 non-AIDS-related deaths (2 major adverse cardiovascular events, 1 Hodgkin lymphoma, 1 bacterial pneumonia, 1 suicide, 1 unspecified non-AIDS event). Abbreviation: BL, baseline.

Figure 2.

Time to occurrence of new AIDS-related events or AIDS-related death. Fifteen people with HIV developed 24 new AIDS events or died an AIDS-related death (incidence rate, 3.52/100 person-years of follow-up; 95% CI, 2.12–4.94): 3 atypical mycobacteriosis, 3 pulmonary tuberculosis, 1 tuberculous meningoencephalitis, 2 non-Hodgkin lymphoma, 1 cutaneous Kaposi sarcoma, 2 esophageal candidiasis, 2 Pneumocystis jirovecii pneumonia, 1 disseminated herpes simplex, 1 wasting syndrome, 1 cryptococcal meningitis, 1 cytomegalovirus encephalitis, and 6 AIDS-related deaths. Abbreviation: BL, baseline.

Figure 3.

Time to occurrence of new non-AIDS-related events or non-AIDS-related death. Twenty-six people with HIV developed 38 non-AIDS events or died a non-AIDS related death (incidence rate, 5.59/100 person-years of follow-up; 95% CI, 3.81–7.37): 3 Hodgkin lymphoma, 4 anal cancer, 3 hepatocellular carcinoma, 2 prostate cancer, 1 lung cancer, 1 breast cancer, 1 laryngeal cancer, 1 conjunctival spinocellular carcinoma, 1 squamous cell skin cancer, 6 major adverse cardiovascular events, 6 chronic kidney disease, 3 cirrhosis, and 6 non-AIDS-related deaths. Abbreviation: BL, baseline.