Multidisciplinary Collaborative Integrated Management of Increasingly Prominent HIV Complications in the Post-cART Era

L Lin; TS Li


HIV Medicine. 2020;21(11):683-691. 

In This Article

Dementia is Associated With Changes in Cerebrovascular Elasticity

Despite the extensive use of cART, cognitive impairment remains prevalent in PLWH, potentially due to, in part, damage to small blood vessels in the brain.[15] Cerebrovascular endothelial dysfunction may be an independent factor, leading to cognitive impairment in PLWH. A simple auxiliary examination to determine cerebrovascular endothelial function may identify an individual's risk of cognitive dysfunction at an early stage and reduce dementia's irreversible loss. Cerebral vasoreactivity is an index of cerebrovascular endothelial function that can be non-invasively assessed by transcranial Doppler ultrasound and is associated with both cerebral small vessel disease and severe AS, which are two common stroke mechanisms in HIV infection. By utilizing the breath-holding challenge to measure cerebral vasoreactivity, poor cerebral vasoreactivity indicates poor cerebrovascular endothelial function. We concluded that women, a longer duration of HIV diagnosis, and higher high-sensitivity C-reactive protein were associated with poorer cognitive performance.[16] PLWH with low total cholesterol who received cART and had virological inhibition had poorer cerebral vasoreactivity than non-HIV-infected controls.[17] With increase in age, traditional vascular risk factors, such as dyslipidaemia, become increasingly common, which may play a more important role in the overall stroke risk, masking the impact of HIV infection. The corollary that should be emphasized is that PLWH without traditional vascular risk factors (such as elevated total cholesterol) may still have an increased cerebrovascular risk compared with uninfected individuals.

In addition to the direct effects of the virus, the effects of cART on the central nervous system also need to be evaluated. We found that lopinavir/ritonavir (LPV/r) use was associated with reduced cerebral vasoreactivity in 3TC combined with TDF or ZDV compared with EFV.[17] The CACT data showed that endothelial dysfunction associated with PI use might extend from the systemic vascular system to the brain and provide a possible mechanism to explain the higher risk of non-haemorrhagic stroke events associated with PI exposure in HIV-infected individuals and the pathology of cerebral small-vessel disease.[17] Although ZDV and NVP are no longer first-line recommended drugs, some patients in China still maintain the antiviral treatment of 3TC + ZDV + NVP. ZDV and NVP both have good cerebrospinal fluid permeability. For PLWH who have progressive multifocal leukoencephalopathy, the cART regimen could considerably be adjusted to contain ZDV, NVP or dolutegravir (DTG). The use of DTG should also refer to the patient's economic purchasing ability.

Efavirenz-based cART was included in China's first-line recommended antiviral therapy in 2011. A meta-analysis published in July 2014 in the Annals of Internal Medicine found that suicidal ideation and attempts were twice as common in the EFV group as in other cART regimens. The rapid increase in the rate of change and withdrawal of EFV during long-term follow-up may also be due to patients' psychological adverse reactions, which is the main reason for the decline in the long-term treatment effect. The CACT data showed that patients were grouped according to their body weight with 60 kg as the cut-off value, and the blood concentration of EFV in the low-weight group was significantly higher than that in the high-weight group. Plasma EFV concentration significantly negatively correlated with body weight and was higher in patients with low body weight.[18] Chinese patients with AIDS have higher concentrations of EFV. We further recommend that Chinese patients with AIDS, especially those of low weight, be given a 400 mg dose of EFV, which can significantly reduce neurological adverse reactions, thus updating this decision in the Chinese guidelines for diagnosis and treatment of HIV/AIDS 2018.[1]