Weight Gain After HIV Therapy Initiation: Pathophysiology and Implications

Chandiwana, Nomathemba; Siedner, Mark J.; Marconi, Vincent C.; Hill, Andrew; Ali, Mohammed K.; Batterham, Rachel L.; Venter, François

doi:10.1210/clinem/dgad411

Cited by 3 publications

(3 citation statements)

References 96 publications

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“…In turn, HIV infection can diminish epithelial barrier integrity 58 , allowing for microbial translocation that promotes immune activation and chronic inflammation 59,60 . Moreover, obesity has become a major problem for individuals on the latest generation of ART such as dolutegrevir 61 . Very few studies have measured associations between the gut microbiome and HIV status in African populations 13,[62][63][64] , where baseline microbiome composition and disease profiles are distinct from those observed in HICs.…”

Section: Gut Microbiome Associations With Hiv Statusmentioning

confidence: 99%

Expanding the human gut microbiome atlas of Africa

Maghini,

Oduaran,

Wirbel

et al. 2024

Preprint

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Population studies are crucial in understanding the complex interplay between the gut microbiome and geographical, lifestyle, genetic, and environmental factors. However, populations from low- and middle-income countries, which represent ~84% of the world population, have been excluded from large-scale gut microbiome research. Here, we present the AWI-Gen 2 Microbiome Project, a cross-sectional gut microbiome study sampling 1,803 women from Burkina Faso, Ghana, Kenya, and South Africa. By intensively engaging with communities that range from rural and horticultural to urban informal settlements and post-industrial, we capture population diversity that represents a far greater breadth of the world's population. Using shotgun metagenomic sequencing, we find that study site explains substantially more microbial variation than disease status. We identify taxa with strong geographic and lifestyle associations, including loss of Treponema and Cryptobacteroides species and gain of Bifidobacterium species in urban populations. We uncover a wealth of prokaryotic and viral novelty, including 1,005 new bacterial metagenome-assembled genomes, and identify phylogeography signatures in Treponema succinifaciens. Finally, we find a microbiome signature of HIV infection that is defined by several taxa not previously associated with HIV, including Dysosmobacter welbionis and Enterocloster sp. This study represents the largest population-representative survey of gut metagenomes of African individuals to date, and paired with extensive clinical biomarkers, demographic data, and lifestyle information, provides extensive opportunity for microbiome-related discovery and research.

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Section: Gut Microbiome Associations With Hiv Statusmentioning

confidence: 99%

Expanding the human gut microbiome atlas of Africa

Maghini,

Oduaran,

Wirbel

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Current cardiovascular disease risk calculators underestimate the risk in PWH because they fail to take this into account [19,20]. Noncommunicable diseases including cardiovascular conditions are now also leading causes of mortality for PWH, threatening the near-normal life expectancy that PWH should otherwise experience with effective ART [21 ▪▪ ,22]. However, caution is needed when applying this narrative in some emerging economy settings.…”

Section: Obesity In People With Hivmentioning

confidence: 99%

“…The relative impact of ART exposure as an independent driver of weight change is therefore a pertinent and dynamic field of investigation [21 ▪▪ ]. Pharmaceutical manufacturers have much to lose if newer ART drugs under patent monopoly prices are identified as causing obesity.…”

Section: Weight Gain and Antiretroviral Therapymentioning

confidence: 99%

Intersections between HIV and obesity in emerging economies

Levi,

Fairhead,

Hill

2023

Current Opinion in HIV and AIDS

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Purpose of review HIV epidemics are increasing in many emerging economy countries, whilst the very process of ‘economic emergence’ is obesogenic. Annual deaths related to obesity and overweight are now four times more than for HIV globally. We describe the intersections between HIV and obesity in emerging economies, and highlight potential mitigation options, including antiobesity medications (AOMs), which are safe and effective, but inaccessibly priced. Recent findings We summarize what is known about weight-change in HIV and review strategies including public health policies and clinical interventions for emerging economy countries to fight obesity. We also illustrate the landscape from a selection of ‘emerging economy’ countries with available data from UNAIDS, World Bank and World Obesity Federation to visualize the developing challenges faced. AOM course prices are high in many countries, but could be manufactured and sold profitably for much less. We present lessons from the early HIV/AIDS movements on how to improve access and pricing for AOMs for people with HIV with obesity in emerging economy countries. Summary We illustrate the complex intersectional issues that ‘emerging economy countries’ may experience, with a ‘double burden’ of increasing HIV and obesity epidemics, and explore potential mitigation options, focussing on AOM access and pricing.

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Recent data on the role of antiretroviral therapy in weight gain and obesity in persons living with HIV

Capeau,

Lagathu,

Béréziat

2023

Current Opinion in HIV and AIDS

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Purpose of review Antiretroviral therapy (ART) has long been implicated in fat alterations and weight variations leading to cardiometabolic consequences. Recent largely prescribed antiretrovirals (ARVs) from the integrase-strand-transfer-inhibitor (INSTI) class have been associated with excessive weight gain/obesity in a minority of persons with HIV (PWH). As well, in the nucleoside reverse transcriptase inhibitors (NRTI) class, tenofovir-alafenamide (TAF), often replacing tenofovir-disoproxil-fumarate (TDF), has been associated with weight gain, a worrying concern in the present worldwide obesogenic environment. The respective role of the different ARV, the risk factors and the mechanisms remain questionable. Recent findings The INSTIs dolutegravir (DTG) and bictegravir (BIC) and TAF have a proper effect on weight gain, while efavirenz (EFV) and TDF inhibit it. These effects are reported in ART-naïve PWH, in addition to weight gain resulting from the return to health process, and in ART-controlled PWH. Also, INSTIs induce weight gain in adolescents and excessive weight gain during pregnancy. The effects of INSTIs and TAF are additive. Their trajectory differs. Most of the weight gain is observed during the initial 12-month period. The main risk factors are low CD4+ and high viral load (VL) in ART-naïve PWH, Black race or originating from some African countries and female gender. The role of age and BMI differs between studies. The reversibility of the effect of INSTI and TAF appears limited. Regarding the mechanisms, the INSTIs can directly alter adipose tissue in particular through inhibition of fat beiging, resulting in fat fibrosis and hypertrophy. Macrophage infiltration is decreased. The mechanisms explaining the opposite effects of TDF and TAF remain elusive. Summary The specific impact of DTG, BIC and TAF on weight gain/obesity in PWH is confirmed in different populations independently of the weight limiting effect of EFV and TDF. ART-linked excessive weight gain is uncommon. African origin and female sex are risk factors that need to be considered. The mechanisms are better understood for INSTIs but unknown for TDF/TAF. The reversibility of weight gain/obesity when stopping INSTI or TAF remains limited.

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Weight Gain After HIV Therapy Initiation: Pathophysiology and Implications

Cited by 3 publications

References 96 publications

Expanding the human gut microbiome atlas of Africa

Expanding the human gut microbiome atlas of Africa

Intersections between HIV and obesity in emerging economies

Recent data on the role of antiretroviral therapy in weight gain and obesity in persons living with HIV

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