HIV-Related Neuropathology, 1985 to 1999: Rising Prevalence of HIV Encephalopathy in the Era of Highly Active Antiretroviral Therapy

Abstract

Postmortem neuropathologic reports for a consecutive series of 436 HIV-seropositive patients who died between 1985 and 1999 were matched with clinical data for 371 of them. Cases were divided into four groups depending on the date of death. The chosen time periods reflected the type of antiretroviral therapy available: before 1987 (before zidovudine); 1987-1992, the period of monotherapy (nucleoside analog reverse transcriptase inhibitors [NRTIs]); 1993-1995, the era of the use of dual NRTI combinations; and 1996-1999, the era of highly active antiretroviral therapy (HAART) containing protease inhibitors. Fifty-seven percent of our cases in this group had been prescribed HAART. In our study population, accessibility to the latest antiretroviral therapy was widespread. The total number of HIV autopsies declined after the advent of combination therapy. The prevalence of opportunistic infections-cytomegalovirus, toxoplasmosis, cryptococcosis, and central nervous system lymphoma-decreased over time. Cerebral tuberculosis, aspergillosis, herpes, and progressive multifocal leukoencephalopathy showed a downward trend, but the numbers were too low for statistical analyses. The incidence of HIV encephalopathy increased over time (p =.014). The rising prevalence of HIV encephalopathy at time of death may reflect a longer survival time after initial HIV infection in the HAART era. Although combination therapies decrease overall mortality and prevalence of CNS opportunistic infections, these therapies may be less active in preventing direct HIV-1 effects on the brain.

Rapidly Progressed Acquired Immunodeficiency Syndrome Dementia Complex as an Initial Manifestation

“…Although the incidence of all opportunistic infections has declined dramatically in the era of potent antiretroviral therapy, the prevalence of HIV-associated brain disease or encephalopathy is rising despite supportive antiretroviral therapy (8). On the other hand, marked improvement in survival following onset of ADC in the era of potential antiviral therapy also has been reported (9).…”

Alterações cognitivas na infecção pelo HIV e Aids

“…Esta taxa não foi alterada pela HAART 28 . Ao contrário, Neuenburg et al (2002) 29 encontraram aumento da incidência de encefalopatia pelo HIV com o passar do tempo.…”

“…A HAART prolonga a vida e restaura a resposta imune para patógenos não-HIV, mas não previne a patologia direta relacionada ao HIV no cérebro, apesar de diminuir a gravidade dos achados anátomo-patológicos em autópsias 29 . Nos últimos anos ocorreu diminuição da incidência de doenças neurológicas, tanto as secundárias (oportunísticas), quanto as primárias (demência ligada ao HIV).…”

“…Nos últimos anos ocorreu diminuição da incidência de doenças neurológicas, tanto as secundárias (oportunísticas), quanto as primárias (demência ligada ao HIV). No entanto, a demência associada ao HIV continua a ser a causa mais comum de demência em jovens com idade inferior a 40 anos 25,[29][30][31] .…”

“…Com a HAART, a incidência da demência associada ao HIV vem diminuindo 26,29,32 , mas a prevalência aumentando devido a maior sobrevida dos pacientes infectados pelo HIV e o aparecimento de formas mais leves de dano cognitivo 33 .…”