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More affirmation that HIV integrase inhibitor assay is associated with weight gain, and that bodies accretion added weight afterwards alpha assay with an integrase inhibitor than bodies demography added biologic classes, was presented this anniversary at the Appointment on Retroviruses and Opportunistic Infections (CROI 2019) in Seattle.

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Weight accretion on integrase inhibitor assay was aboriginal flagged up in backward 2018 and, back the aboriginal reports, added assay groups accept been attractive at weight accretion in a added ambit of accommodating groups.

The anatomy of weight accretion apparent in bodies starting integrase inhibitor assay is not the aforementioned as the fat redistribution syndrome, or lipodystrophy, empiric back the aboriginal bearing of protease inhibitors was acclimated in aggregate with nucleoside about-face transcriptase inhibitors (NRTIs) or back non-nucleoside about-face transcriptase inhibitors (NNRTIs) were acclimated in aggregate with earlier NRTIs, abnormally stavudine (d4T).

Whereas lipodystrophy complex accession of axial belly or belly fat, and accident of subcutaneous fat, weight accretion on avant-garde antiretroviral assay consists of accepted fat accretion – both subcutaneous and axial fat – with an access in waist circumference.

Weight accretion afterwards starting antiretroviral assay is a accepted event; accepting a bashful bulk of weight is normal, abnormally in bodies with added avant-garde HIV ache or low anatomy accumulation above-mentioned to treatment. It’s been dubbed ‘return to health’ weight gain.

However, what has been apparent with some biologic regimens – not aloof integrase inhibitors, but some protease inhibitors too – is added abundant weight gain. Some clinicians accept aloft apropos that weight accretion ability eventually access cardiovascular ache risks, claret burden and blazon 2 diabetes in populations which already accept a aerial prevalence of blubber and added accident factors for cardiovascular disease. The VACS abstraction showed that accepting bristles pounds (2.26kg) afterwards starting assay added the accident of diabetes by 14%, while the D:A:D accomplice begin that every assemblage of anatomy accumulation access afterwards starting antiretroviral assay aloft the accident of diabetes by 13%.

But is this weight accretion acquired by antiretroviral drugs or is it a artefact of environments that animate bodies to eat unhealthily and be physically inactive? Moderating a altercation on weight accretion afterwards starting treatment, Jane O’Halloran of Washington University, St Louis, acicular out that up to bisected of adults starting antiretroviral assay in the United States may already be obese. Weight accretion afterwards starting assay may be occurring in adults who already accept diets and lifestyles that activate them to added weight gain.

On the added hand, asked Carl Fichtenbaum of University of Cincinatti, what if weight accretion on regimens added than integrase inhibitors is actuality blunted by furnishings of assertive drugs on fat deposits?

Studies presented at CROI this anniversary attempted to afford added ablaze on the problem, specifically: whether integrase inhibitors annual added weight accretion than added drugs; how abundant weight is actuality acquired and over what period; who ability be at greater risk; and whether there is any aberration amid integrase inhibitors.

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The better abstraction to address on this question, the North American AIDS Accomplice Collaboration, begin that amid bodies starting assay for the aboriginal time, assay with dolutegravir or raltegravir was associated with greater weight accretion than assay with NNRTI-based treatment. The accomplice assay looked at 24,001 bodies who started assay amid 2007 and 2015. During that period, 4740 bodies started assay with an integrase inhibitor (1681 raltegravir, 2124 elvitegravir and 935 dolutegravir).

After bristles years on treatment, bodies demography an integrase inhibitor had acquired a boilerplate of 6kg, compared to 4.3kg for bodies who started an NNRTI (p < 0.001). There was no aberration in weight accretion amid bodies who started an integrase inhibitor or a protease inhibitor. (Bourgi)

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The Women’s Interagency Health Abstraction advised its accomplice of 1118 women who had ephemeral viral endless amid 2008 and 2017 on treatment, 234 of whom switched to an integrase inhibitor during that period. This accomplice had a aerial prevalence of blubber and a beggarly anatomy accumulation basis of aloof over 30 at baseline. There was no cogent aberration in anatomy weight by demographics or by biologic dieting at baseline, with beggarly weight of about 80kg. Women who switched to an integrase inhibitor acquired 2.14kg added than women who did not switch. (Kerchberger)

Dallas Parkland Hospital looked at 4048 patients who started assay amid 2009 and 2017, with boilerplate acknowledgment to antiretroviral assay of 6.7 years. They looked at differences in changes in anatomy accumulation basis afterwards starting assay amid bodies who started regimens based on an NNRTI, a protease inhibitor or an integrase inhibitor.

The boilerplate access in anatomy accumulation basis was greatest in the integrase inhibitor accumulation ( 0.32/m2 per year) and aboriginal in the NNRTI accumulation ( 0.22/mm2 per year). (Bedimo)

In summary, best studies did acquisition an affiliation amid integrase inhibitor assay and weight gain, in ahead basic bodies and in bodies switching from addition regimen.

One abstraction did not acquisition an association. An assay of dispensary databases in 21 US states, accoutrement 3468 bodies with suppressed viral amount for at atomic one year, looked at weight accretion amid 2013 and 2018. They begin that patients acquired an boilerplate of 3% a year in weight, but in a altercation on weight accretion research Grace McComsey acicular out that best bodies are not accepting abundant weight – “only 30% acquired added than 3%”.

Regression assay bootless to appearance an affiliation amid integrase inhibitor assay and weight gain. Instead, cogent predictors of weight accretion in this citizenry were low anatomy accumulation basis at baseline, actuality ample at baseline, hypogonadism (low testosterone), protease inhibitor treatment, and psychiatric disorder. (McComsey)

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The HIV blockage abstraction HPTN 077 looked at weight accretion in 199 HIV-negative bodies who accustomed articulate consecration assay and consecutive injectable cabotegravir. Weight was abstinent at anniversary abstraction appointment to anniversary 41 and no aberration in weight accretion was apparent amid those who accustomed cabotegravir or placebo – both groups acquired about 1kg. The board commented that an alternation amid HIV infection and integrase inhibitor assay may be an important contributor to weight accretion on antiretroviral treatment. (Landovitz)

A analysis of 972 bodies who switched to an integrase inhibitor in AIDS Clinical Trials Accumulation studies begin that in the two years afterwards switching, white or atramentous race, age 60 or over, or a pre-switching anatomy accumulation basis of 30 or aloft (obese) were associated with greater weight accretion in women. In men, alone age over 60 was associated with weight gain. Dolutegravir was associated with the greatest weight accretion and the assets in weight afterwards starting assay were beyond than those accepted for a person’s age. (Lake)

A analysis of 437 patients in the HIV Outpatients Abstraction begin that amid patients who switched to integrase inhibitor-based assay afterwards viral abolishment on addition regimen, weight accretion was decidedly greater in non-Hispanic atramentous patients and in bodies with no above-mentioned history of nucleoside about-face transcriptase inhibitor use. (Palella)

In the NACCORD study, advisers looked at weight accretion afterwards two years on anniversary integrase inhibitor and compared this with weight acquired by bodies starting assay with an NNRTI or a protease inhibitor. Demography into annual that beneath bodies accustomed dolutegravir because it was accountant afterwards raltegravir and elvitegravir, the board begin that patients on raltegravir or dolutegravir acquired decidedly added weight than bodies demography NNRTI treatment, while bodies demography elvitegravir acquired beneath weight than bodies demography a protease inhibitor.

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In the Parkland abstraction discussed in a antecedent section, women acquired added weight than men on dolutegravir and raltegravir, but not on elvitegravir. Atramentous bodies acquired added than added indigenous groups on dolutegravir, but not on added integrase inhibitors. In the absolute cohort, bodies demography elvitegravir acquired added weight than bodies demography dolutegravir or raltegravir. (Bedimo)

In summary, no bright arrangement emerged from the assay presented at CROI apropos the furnishings of assorted integrase inhibitors.

References

Bedimo R et al. Differential BMI changes afterward PI- and InSTI-based ART admission by sex and race. Appointment on Retroviruses and Opportunistic Infections, Seattle, abstruse 675, 2019.

View the abstruse on the appointment website.

Bourgi K et al. Greater weight accretion amid treatment-naïve bodies starting integrase inhibitors. Appointment on Retroviruses and Opportunistic Infections, Seattle, abstruse 670, 2019.

View the abstruse on the appointment website.

Watch the webcast of this affair on the appointment website.

Kerchberger AM et al. Integrase fiber alteration inhibitors are associated with weight accretion in women. Appointment on Retroviruses and Opportunistic Infections, Seattle, abstruse 672, 2019.

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View the abstruse on the appointment website.

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Watch the webcast of this affair on the appointment website.

Lake J et al. Accident factors for weight accretion afterward about-face to integrase inhibitor-based ART. Appointment on Retroviruses and Opportunistic Infections, Seattle, abstruse 669, 2019.

View the abstruse on the appointment website.

Watch the webcast of this affair on the appointment website.

Landovitz RJ et al. Cabotegravir is not associated with weight accretion in HIV-negative individuals: HPTN 077. Appointment on Retroviruses and Opportunistic Infections, Seattle, abstruse 34LB.

View the abstruse on the appointment website.

Watch the webcast of this affair on the appointment website.

McComsey GA et al. Weight accretion during assay amid 3.468 treatment-experienced adults with HIV. Appointment on Retroviruses and Opportunistic Infections, Seattle, abstruse 671, 2019.

View the abstruse on the appointment website.

Watch the webcast of this affair on the appointment website.

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Palella FJ et al. Weight accretion amid virally suppressed bodies who about-face to InSTI-based ART. Appointment on Retroviruses and Opportunistic Infections, Seattle, abstruse 674, 2019.

View the abstruse on the appointment website.

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