{"id":42544,"date":"2022-04-01T07:38:28","date_gmt":"2022-04-01T07:38:28","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=42544"},"modified":"2023-07-23T19:41:55","modified_gmt":"2023-07-23T19:41:55","slug":"croi-2022-risk-factors-for-nafld-and-proteinuria-in-hiv-positive-people-on-art-in-reprieve-study","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/42544","title":{"rendered":"CROI 2022: Risk factors for NAFLD and proteinuria in HIV positive people on ART in the REPRIEVE study"},"content":{"rendered":"
Kirk Taylor, HIV i-Base<\/span><\/strong><\/div>\n
\n

\"CROIREPRIEVE is a large international clinical study of cardiovascular disease (CVD) risk factors in people with HIV (PWH). Participants were randomised to daily statins or placebo. A sub-study recently reported increased ECG abnormalities for 44% of participants. [1]<\/b><\/p>\n<\/div>\n

Two further REPRIEVE sub-studies that assessed non-alcoholic fatty liver disease (NAFLD) and proteinuria were presented at CROI 2022.<\/p>\n

NAFLD was identified in 20% of sub-study participants. Risk factors for NAFLD were BMI >30 kg\/m2<\/sup>, metabolic syndrome and being male. [2]<\/p>\n

Relative risk of kidney disease was elevated in women, living in lower income countries, hypertension and TDF use. [3]<\/p>\n

The double-blind REPRIEVE trial (NCT02344290) enrolled 7,770 people living with HIV on ART, aged between 40 to 75 years. Participants were randomised to daily pitavastatin (4 mg QD) or placebo.<\/p>\n

Several sub-studies are embedded within the trial to evaluate CVD risk.<\/p>\n

NAFLD reported for 1 in 5 participants in sub-study<\/h2>\n

NAFLD is common in people living with HIV and associated with increased CVD risk. Data from the mechanistic sub-study reported risk factors for NAFLD and inflammatory markers. [2]<\/p>\n

Participants undergoing non-contrast CT scans were included in the study (n=655).<\/p>\n

Clinical criteria for NAFLD were hepatic steatosis <40 HU or liver to spleen ratio <1.0. Steatosis was recorded in 21% of participants (139\/655). Exclusion of participants that reported drinking >1 to 2 units per day, led to NAFLD diagnosis for 1 in 5 participants (97\/477).<\/p>\n

Participants in the NAFLD group were male (82%) and aged >40. Ethnicity was White (63%), Black or African American (20%), Hispanic or Latinx (34%).<\/p>\n

BMI was 25 to 29.9 kg\/m2<\/sup> in 42% of participants and >30 kg\/m2<\/sup> in 45%; 51% had elevated waist circumference.<\/p>\n

Average ASCVD risk scores in the NAFLD group were 5.8 (95% CI: 3.3 to 7.7, p=0.002). Scores indicated borderline or intermediate risk of atherosclerotic disease in 60% of participants.<\/p>\n

The NAFLD group also had elevated liver enzymes (ALT; 45% vs 25%, p=0.001) and were more likely to have history of an AIDS-defining event.<\/p>\n

NAFLD risk factors were BMI >30 kg\/m2<\/sup> (RR: 1.76; 95% CI: 1.21 to 2.57) and metabolic syndrome (RR: 1.56, 95% CI: 1.06 to 2.30), whilst females had reduced risk (RR: 0.47, 95% CI: 0.26 to 0.86).<\/p>\n

Time since HIV diagnosis, CD4 count, CD4 nadir and viral load were not predictors of NAFLD risk.<\/p>\n

Markers of arterial disease (LpPLA-2) and general inflammation (CRP) were modestly elevated in the NAFLD group but remained within the normal range.<\/p>\n

NAFLD was not associated with ART or HIV-specific measures.<\/p>\n

NAFLD or MAFLD?<\/h2>\n

Guaraldi and colleagues presented data from two cross-sectional studies showing a significant overlap of NAFLD and MAFLD (metabolic dysfunction-associated fatty liver disease) in HIV positive participants. [4]<\/p>\n

MAFLD is emerging as a more sensitive criteria for liver disease than NAFLD. [5]<\/p>\n

Uptake of MAFLD criteria may therefore lead to earlier detection of liver disease in the HIV population.<\/p>\n

Women over 50 with previous TDF use have increased chance of proteinuria<\/h2>\n

People living with HIV have a greater chance of chronic kidney disease, compared to HIV negative people.<\/p>\n

Risk factors for kidney disease (proteinuria and albuminuria) are being evaluated in the REPRIEVE kidney ancillary sub-study are assessing risk factors for kidney disease. [3]<\/p>\n

Participants were split into three groups by proteinuria: normal to mildly increased (n=1963), moderately increased (n=655) or severely increased (n=74).\u00a0Participants were women (38%) and median age was 49 years (IQR: 44 to 54). Ethnicity was Black (48%), White (31%) and Asian (17%). Viral load was <400 copies\/mL (98%) and CD4 counts ranged from 443 to 629 cells\/mm3<\/sup>.<\/p>\n

Risk factors for kidney disease were being female (RR: 1.71, 95%CI: 1.42 to 2.05), aged over 50 (RR: 1.28, 95% CI: 1.06 to 1.78), current smoker (RR: 1.34, 95% CI: 1.12 to 1.61) and history of TDF use (RR: 1.90, 95% CI: 1.43 to 2.67).<\/p>\n

Reduced risk of proteinuria was noted in Black participants and those with BMI <25 kg\/m2<\/sup>.<\/p>\n

Albuminuria was less common (9% of participants) and was associated with hypertension (RR: 1.56, 95% CI: 1.20 to 2.04). Participants on thymidine analogues had reduced risk (RR: 0.42, 95% CI: 0.19 to 0.97).<\/p>\n

Kidney disease was more common in participants recruited from lower income regions (e.g., sub-Saharan Africa and East Asia). This difference may be due to reduced access to prevention services and other factors not covered by this study.<\/p>\n

In summary, REPRIEVE sub-study data indicate associations between NAFLD and increased BMI, metabolic dysfunction, and male sex. Kidney disease was more common in women aged over 50 with history of TDF use.<\/p>\n

\n

comment<\/span><\/h3>\n<\/div>\n
\n

These data highlight CVD risk factors but have not been adjusted for statin use. It will be important to determine whether these associations persist in the unblinded datasets.<\/strong><\/p>\n<\/div>\n

\n

Dr Overton answered questions from Drs Hunt, Mallon and Kallianpur during the poster discussion. Their exchanges highlighted that higher, but non-significant, rates of kidney disease reported from lower income countries may be related to reduced access to treatment and prevention services.<\/strong><\/p>\n<\/div>\n

\n

Associations between women and kidney disease may partly be explained by higher numbers of female participants from lower income countries.<\/strong><\/p>\n<\/div>\n

\n

Finally, reduced risk of albuminuria with thymidine analogues may be related to PWH that did not experience side effects and were not switched onto alternatives, such as TDF.<\/strong><\/p>\n<\/div>\n

\n

A patient leaflet on NAFLD and HIV is available from i-Base. [6]<\/strong><\/p>\n<\/div>\n

\n

References<\/span><\/p>\n<\/div>\n

\n
    \n
  1. Collins S. ECG abnormalities reported by 44% of people older than 40 on ART: results from REPRIEVE study. (HTB 20 December 2021).
    \n<\/span>https:\/\/i-base.info\/htb\/41907<\/a><\/li>\n
  2. Fichtenbaum CJ. NAFLD is common and associated with cardiovascular risk in REPRIEVE participants. CROI 2022. 12-16 February 2022, virtual. Poster 520.
    \n    https:\/\/ww2.aievolution.com\/cro2201\/index.cfm?do=abs.viewAbs&abs=1391<\/a><\/li>\n
  3. Overton ET. Proteinuria is common among people with HIV with controlled viremia. CROI 2022. 12-16 February 2022, virtual. Poster 607.
    \n    https:\/\/www.croiconference.org\/abstract\/proteinuria-is-common-among-people-with-hiv-with-controlled-hiv-viremia<\/a><\/li>\n
  4. Guaraldi G. From NAFLD to MAFLD: implications of change in terminology for people with HIV. CROI 2022. 12-16 February 2022, virtual. Poster 521
    \n    https:\/\/www.croiconference.org\/abstract\/from-nafld-to-mafld-implications-of-change-in-terminology-in-pwh\/<\/a><\/li>\n
  5. Yamamura S. MAFLD identifies patients with significant hepatic fibrosis better than NAFLD. Liver International, Vol 40 (12) (3018-3030). DOI:10.1111\/liv.14675 (30 September 2020).
    \n    https:\/\/onlinelibrary.wiley.com\/doi\/epdf\/10.1111\/liv.14675<\/a><\/li>\n
  6. i-Base. NAFLD: HIV and fatty liver disease. (September 2019).
    \n    https:\/\/i-base.info\/guides\/side\/hiv-and-fatty-liver-disease<\/a>.<\/li>\n<\/ol>\n

    This report was first published on 17 March 2022.<\/em><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

    Kirk Taylor, HIV i-Base REPRIEVE is a large international clinical study of cardiovascular disease (CVD) risk factors in people with HIV (PWH). Participants were randomised to daily statins or placebo. A sub-study recently reported increased ECG abnormalities for 44% of …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,31],"tags":[318],"class_list":["post-42544","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-opportunistic-infections-coinfections-and-complications","tag-croi-2022"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/42544","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=42544"}],"version-history":[{"count":2,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/42544\/revisions"}],"predecessor-version":[{"id":45807,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/42544\/revisions\/45807"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=42544"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=42544"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=42544"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}