Antiretroviral therapy for HIV controllers: Reasons for initiation and outcomes in the French ANRS-CO21 CODEX cohort

Plaçais, Léo; Boufassa, Faroudy; Lécuroux, Camille; Gardiennet, Elise; Avettand-Fènoël, Véronique; Sáez‐Cirión, Asier; Lambotte, Olivier; Noël, Nicolas

doi:10.1016/j.eclinm.2021.100963

Cited by 6 publications

(6 citation statements)

References 38 publications

(59 reference statements)

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“…This is a matter of debate, as international recommendations claim for an early introduction of ART in PLWH. HICs might start therapy for 2 main reasons: mainly a decline in the CD4 levels (independently of viral control loss) or viral control loss [ 29 , 40 ]. We had already shown that clinical events leading to CD4 decline were scarcely reported [ 29 ] and mainly consisted of nonsevere infections, as reported in our current study.…”

Section: Discussionmentioning

confidence: 99%

“…We had already shown that clinical events leading to CD4 decline were scarcely reported [ 29 ] and mainly consisted of nonsevere infections, as reported in our current study. However, studies analyzing the effect of ART in HICs have mainly shown an effect on the HIV VL and immune activation parameters, but data on CD4 T-cell counts or CD4:CD8 ratio normalization remain controversial [ 20 , 40 ]. Furthermore, the impact of ART on reducing the risk of nADEs beyond improvement in inflammatory biomarkers has not been firmly proven.…”

Section: Discussionmentioning

confidence: 99%

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Non-AIDS-Defining Events in Human Immunodeficiency Virus Controllers Versus Antiretroviral Therapy–Controlled Patients: A Cohort Collaboration From the French National Agency for Research on AIDS CO21 (CODEX) and CO06 (PRIMO) Cohorts

Manto

Castro

Goujard

et al. 2023

Open Forum Infectious Diseases

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Background Low-grade chronic inflammation may persist in spontaneous HIV controllers (HIC), leading to non-AIDS defining events (nADEs). Methods 227 ART-naïve HIC (known HIV-1 infection ≥5 years and at least 5 last consecutive viral loads (VL) < 400 HIV RNA copies/mL) were compared with 328 patients who initiated ART ≤1 month after primary HIV-infection diagnosis, had undetectable VL within 12 months following ART initiation for at least 5 years (“ART-patients”). Incidence rates (IR) of first nADEs were compared between HIC and ART-treated-patients. Determinants of nADEs were assessed by using Cox regression models. Results All-cause nADEs incidence rates were 7.8 [5.9-9.6] per 100 person-months (pm) and 5.2 [3.9-6.4] per 100 pm among HIC and ART patients, respectively (Incidence Rate Ratio (IRR)=1.5 [95%Confidence Interval (CI95%), [1.1-2.2] and after adjustment IRR was (1.93; CI95% [1.16-3.20]). After adjustment for the cohort, demographic and immunological characteristics, the only other factor associated with all-cause nADEs occurrence was age ≥43 (vs.<43) years at the beginning of viral control (IRR=1.69 [1.11-2.56]). The most frequent events observed in the 2 cohorts were non-AIDS-related benign infections (54.6 and 32.9% of all nADEs, respectively for HIC and ART patients). No differences in cardiovascular or psychiatric events were observed. Conclusion HIC experienced two times more often nADEs than virologically suppressed patients on ART, mainly non-AIDS related benign infections. Older age was associated with nADEs occurrence, independently of immune or virologic parameters. These results do not argue in favor of expanding the ART indication for HIC but rather a case-by-case approach considering clinical outcomes such as nADEs besides immune activation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Non-AIDS-Defining Events in Human Immunodeficiency Virus Controllers Versus Antiretroviral Therapy–Controlled Patients: A Cohort Collaboration From the French National Agency for Research on AIDS CO21 (CODEX) and CO06 (PRIMO) Cohorts

Manto

Castro

Goujard

et al. 2023

Open Forum Infectious Diseases

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“… 44 These findings point to the probable coexistence of different mechanisms of HIV persistence (clonal amplification and ongoing replication) in EC, VC and treated subjects and further support that ART may provide and additional layer of protection to some EC, by further reducing the level of residual HIV replication and ongoing viral evolution. 45 , 46 , 47 , 48 …”

Section: Discussionmentioning

confidence: 99%

Ongoing HIV-1 evolution and reservoir reseeding in two elite controllers with genetically diverse peripheral proviral quasispecies

Azevedo

Côrtes

Villela

et al. 2023

Mem. Inst. Oswaldo Cruz

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BACKGROUND Elite controllers (EC) are human immunodeficiency virus (HIV)-positive individuals who can maintain low viral loads for extended periods without antiretroviral therapy due to multifactorial and individual characteristics. Most have a small HIV-1 reservoir composed of identical proviral sequences maintained by clonal expansion of infected CD4 + T cells. However, some have a more diverse peripheral blood mononuclear cell (PBMC)-associated HIV-1 reservoir with unique sequences. OBJECTIVES To understand the turnover dynamics of the PBMC-associated viral quasispecies in ECs with relatively diverse circulating proviral reservoirs. METHODS We performed single genome amplification of the env gene at three time points during six years in two EC with high intra-host HIV DNA diversity. FINDINGS Both EC displayed quite diverse PBMCs-associated viral quasispecies (mean env diversity = 1.9-4.1%) across all time-points comprising both identical proviruses that are probably clonally expanded and unique proviruses with evidence of ongoing evolution. HIV-1 env glycosylation pattern suggests that ancestral and evolving proviruses may display different phenotypes of resistance to broadly neutralising antibodies consistent with persistent immune pressure. Evolving viruses may progressively replace the ancestral ones or may remain as minor variants in the circulating proviral population. MAIN CONCLUSIONS These findings support that the high intra-host HIV-1 diversity of some EC resulted from long-term persistence of archival proviruses combined with the continuous reservoir’s reseeding and low, but measurable, viral evolution despite undetectable viremia.

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“…People with HIV who have low or undetectable HIV RNA levels without taking ART (“elite controllers”) have elevated levels of inflammation that are reduced after ART is initiated . In addition, even those who manifest low viral loads initially often do not maintain control over time . Based on the theoretical benefits of reducing inflammation in people with HIV, treating elite controllers is reasonable.…”

Section: Initiation Of Artmentioning

confidence: 99%

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Gandhi

Bedimo

Hoy

et al. 2023

JAMA

260

148

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ImportanceRecent advances in treatment and prevention of HIV warrant updated recommendations to guide optimal practice.ObjectiveBased on a critical evaluation of new data, to provide clinicians with recommendations on use of antiretroviral drugs for the treatment and prevention of HIV, laboratory monitoring, care of people aging with HIV, substance use disorder and HIV, and new challenges in people with HIV, including COVID-19 and monkeypox virus infection.Evidence ReviewA panel of volunteer expert physician scientists were appointed to update the 2020 consensus recommendations. Relevant evidence in the literature (PubMed and Embase searches, which initially yielded 7891 unique citations, of which 834 were considered relevant) and studies presented at peer-reviewed scientific conferences between January 2020 and October 2022 were considered.FindingsInitiation of antiretroviral therapy (ART) is recommended as soon as possible after diagnosis of HIV. Barriers to care should be addressed, including ensuring access to ART and adherence support. Integrase strand transfer inhibitor–containing regimens remain the mainstay of initial therapy. For people who have achieved viral suppression with a daily oral regimen, long-acting injectable therapy with cabotegravir plus rilpivirine given as infrequently as every 2 months is now an option. Weight gain and metabolic complications have been linked to certain antiretroviral medications; novel strategies to ameliorate these complications are needed. Management of comorbidities throughout the life span is increasingly important, because people with HIV are living longer and confronting the health challenges of aging. In addition, management of substance use disorder in people with HIV requires an evidence-based, integrated approach. Options for preexposure prophylaxis include oral medications (tenofovir disoproxil fumarate or tenofovir alafenamide plus emtricitabine) and, for the first time, a long-acting injectable agent, cabotegravir. Recent global health emergencies, like the SARS-CoV-2 pandemic and monkeypox virus outbreak, continue to have a major effect on people with HIV and the delivery of services. To address these and other challenges, an equity-based approach is essential.Conclusions and RelevanceAdvances in treatment and prevention of HIV continue to improve outcomes, but challenges and opportunities remain.

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Antiretroviral therapy for HIV controllers: Reasons for initiation and outcomes in the French ANRS-CO21 CODEX cohort

Cited by 6 publications

References 38 publications

Non-AIDS-Defining Events in Human Immunodeficiency Virus Controllers Versus Antiretroviral Therapy–Controlled Patients: A Cohort Collaboration From the French National Agency for Research on AIDS CO21 (CODEX) and CO06 (PRIMO) Cohorts

Non-AIDS-Defining Events in Human Immunodeficiency Virus Controllers Versus Antiretroviral Therapy–Controlled Patients: A Cohort Collaboration From the French National Agency for Research on AIDS CO21 (CODEX) and CO06 (PRIMO) Cohorts

Ongoing HIV-1 evolution and reservoir reseeding in two elite controllers with genetically diverse peripheral proviral quasispecies

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

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