Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Günthard, Huldrych F.; Saag, Michael S.; Benson, Constance A.; Rı́o, Carlos del; Eron, Joseph J.; Gallant, Joel E.; Hoy, Jennifer; Mugavero, Michael J.; Sax, Paul E.; Thompson, Melanie; Gandhi, Rajesh T.; Landovitz, Raphael J.; Smith, Davey M.; Jacobsen, Donna M.; Volberding, Paul A.

doi:10.1001/jama.2016.8900

Cited by 537 publications

(315 citation statements)

References 172 publications

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“…The efficacy of treatment as a means of prevention has already been documented for HIV. 5 Field trials could generate the evidence needed to develop effective HCV-prevention programs, particularly in communities with new substance-use and HCV epidemics. Studies are also needed to examine how HCV therapies can interrupt other modes of transmission, including mother-to-child transmission and sexual transmission, particularly among HIV-infected men who have sex with men.…”

mentioning

confidence: 99%

Hepatitis C in Injection-Drug Users — A Hidden Danger of the Opioid Epidemic

Liang

Ward²

2018

N Engl J Med

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confidence: 99%

Hepatitis C in Injection-Drug Users — A Hidden Danger of the Opioid Epidemic

Liang

Ward²

2018

N Engl J Med

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“…To date, PrEP scale-up in Canada has focused primarily on MSM because of the availability of clear data on how to identify high-incidence subpopulations and on the feasibility of PrEP implementation. The use of clinical markers, such as antecedent sexually transmitted infection or use of validated risk calculators (30)(31)(32)(33)(34) allows for the identification of Canadian MSM with HIV incidence rates well over internationally-recommended thresholds of 2-3% per year (35,36 …”

Section: Challenges and Opportunities For Biomedical Prevention Identmentioning

confidence: 99%

Setting the stage for expanding HIV pre-exposure prophylaxis use in Canada

Hull

Dhs

2017

Canada Communicable Disease Report

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Human immunodeficiency virus (HIV) infection continues to disproportionately affect vulnerable populations in Canada; particularly men who have sex with men (MSM). Novel HIV prevention strategies have recently expanded from the use of non-occupational post-exposure prophylaxis (nPEP) after high risk exposures to the use of pre-exposure prophylaxis (PrEP) in which individuals reduce risk of HIV infection through use of combination antiretrovirals taken prior to risk exposure. With approval of tenofovir/emtricitabine (TDF/FTC) for use as PrEP only in early 2016, and with limited public funding to date, uptake in Canada is in its preliminary stages. These biomedical prevention strategies have proven efficacy for MSM, and they may have potential for other at-risk populations. With generic formulations of TDF/FTC now available in Canada, there is an opportunity for widespread implementation. Expanding knowledge of health care providers across Canada on how best to assess, refer for or prescribe and monitor PrEP will contribute to the current efforts to reach the global goal of eliminating new HIV infections.Affiliations

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“…However, the guidelines acknowledge that the threshold of 1000 copies/mL is based on low-quality evidence and, in fact, the optimal threshold for defining virologic failure and for switching ART regimens has not been established. In contrast, European [5] and North American [6] guidelines suggest to switch at much lower thresholds, namely above 50 and 200 copies/mL, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…In high-income settings with easy access to VL monitoring, individualized patient management and a “watch-and-wait” strategy with monthly monitoring for patients with low-level viremia may be appropriate [5, 6]. However, if patients in resource-limited settings with a VL below 1000 copies/mL are defined as “non-failures”, they will not receive any follow-up VL for at least 6 to 12 months – depending on the frequency of VL monitoring recommended in national guidelines and on the availability of VL in a given setting – and may thus continue a failing regimen for considerable time.…”

Section: Introductionmentioning

confidence: 99%

SESOTHO trial (“Switch Either near Suppression Or THOusand”) – switch to second-line versus WHO-guided standard of care for unsuppressed patients on first-line ART with viremia below 1000 copies/mL: protocol of a multicenter, parallel-group, open-label, randomized clinical trial in Lesotho, Southern Africa

Amstutz

Nsakala²,

Vanobberghen

et al. 2018

BMC Infect Dis

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BackgroundThe World Health Organization (WHO) recommends viral load (VL) measurement as the preferred monitoring strategy for HIV-infected individuals on antiretroviral therapy (ART) in resource-limited settings. The new WHO guidelines 2016 continue to define virologic failure as two consecutive VL ≥1000 copies/mL (at least 3 months apart) despite good adherence, triggering switch to second-line therapy. However, the threshold of 1000 copies/mL for defining virologic failure is based on low-quality evidence. Observational studies have shown that individuals with low-level viremia (measurable but below 1000 copies/mL) are at increased risk for accumulation of resistance mutations and subsequent virologic failure. The SESOTHO trial assesses a lower threshold for switch to second-line ART in patients with sustained unsuppressed VL.MethodsIn this multicenter, parallel-group, open-label, randomized controlled trial conducted in Lesotho, patients on first-line ART with two consecutive unsuppressed VL measurements ≥100 copies/mL, where the second VL is between 100 and 999 copies/mL, will either be switched to second-line ART immediately (intervention group) or not be switched (standard of care, according to WHO guidelines). The primary endpoint is viral resuppression (VL < 50 copies/mL) 9 months after randomization. We will enrol 80 patients, giving us 90% power to detect a difference of 35% in viral resuppression between the groups (assuming two-sided 5% alpha error). For our primary analysis, we will use a modified intention-to-treat set, with those lost to care, death, or crossed over considered failure to resuppress, and using logistic regression models adjusted for the prespecified stratification variables.DiscussionThe SESOTHO trial challenges the current WHO guidelines, assessing an alternative, lower VL threshold for patients with unsuppressed VL on first-line ART. This trial will provide data to inform future WHO guidelines on VL thresholds to recommend switch to second-line ART.Trial registrationClinicalTrials.gov (NCT03088241), registered May 05, 2017

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Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Cited by 537 publications

References 172 publications

Hepatitis C in Injection-Drug Users — A Hidden Danger of the Opioid Epidemic

Hepatitis C in Injection-Drug Users — A Hidden Danger of the Opioid Epidemic

Setting the stage for expanding HIV pre-exposure prophylaxis use in Canada

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