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Non-AIDS-events in individuals with spontaneous
control of HIV-1: a systematic review
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Groenendijk, Albert L. MD1; Vos, Wilhelm A.J.W. MD2; dos Santos, Jéssica C. PHD4; Rokx, Casper MD PHD1,3; van der Ven, Andre J.A.M. MD PHD4; Verbon, Annelies MD PHD1
JAIDS Journal of Acquired Immune Deficiency Syndromes: August 15, 2022
Abstract
Background:
Despite antiretroviral treatment (ART), people living with HIV (PLHIV) are at increased risk for non-AIDS-defining events (nADEs), including cardiovascular events, non-AIDS malignances, hepatic disease and bacterial pneumonia.
Setting:
This systematic review seeks to answer the question: are PLHIV who spontaneously control HIV-1 subject to an increased risk of various nADEs relative to non-controlling PLHIV on ART and people without HIV?
Methods:
Databases were searched on June 9, 2021 with a search syntax focused on the elements ‘HIV’, ‘spontaneous control’ and ‘clinical outcomes’: Embase.com (includes Embase and Medline), Medline Ovid (includes PubMed), Cochrane library, Web of Science, Google Scholar. Included were studies reporting non-AIDS events in spontaneous controllers. Excluded were case reports, conference papers, editorials and reviews.
Results:
Of 1134 identified records, 34 were assessed for full-text and 12 studies were included in the qualitative synthesis: five cohorts, two cross-sectional prevalence studies, four cross-sectional imaging studies and one case series. Four of five cohort studies showed that spontaneous controllers have a similar risk to develop nADEs compared with PLHIV on suppressive ART, specifically cardiovascular events, non-AIDS-malignancies, hepatic disease and bacterial pneumonia. Cross-sectional imaging studies showed a higher presence of subclinical cardiovascular disease in spontaneous controllers, like in PLHIV on ART, than in people without HIV.
Conclusion:
individuals with spontaneous control of HIV-1 do not seem to be at a greater risk to develop different nADEs compared with PLHIV on suppressive ART. More data are needed, as the present conclusions are based on a limited number of studies that show a large heterogeneity among them.
A higher coronary artery plaque prevalence in EC compared with controls without HIV [78% (n=7/9) vs. 42% (n=21/49) p=0.03] was reported and a similar coronary artery plaque prevalence of 60% in PLHIV on suppressive ART.6 In another study carotid artery plaque prevalence was reported to be similar between EC, VC, PLHIV on suppressive ART and controls without HIV.32 Of note,
0% and 5% of male and female EC, respectively, and 67.2% and 23.7% of male and female VC
were ART-receiving at time of the different cardiovascular measurements. Coronary artery
calcium determined by CTA was not different between spontaneous controllers and PLHIV on
suppressive ART or people without HIV.6,32 Intima-media-thickness (IMT) in the common
carotid arteries varied from a greater IMT in EC than in controls without HIV (910μm vs. 720 μm; p<0.001)7 to a comparable IMT across EC, VC, PLHIV on suppressive ART and groups
without HIV (table 1B) 32.
PET-CT to determine target-to-background ratios as a measure of aortic inflammation and
cardiovascular disease has been widely used and validated in PLHIV.35,36 Aortic inflammation
on PET-CT was not different between EC relative to people without HIV and PLHIV on
suppressive ART controls (p>0.05).33
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