Newly Acquired Infection With Multidrug-Resistant HIV-1 in a Patient Adherent to Preexposure Prophylaxis

Markowitz, Martin; Grossman, Howard; Anderson, Peter L.; Grant, Robert M.; Gandhi, Monica; Horng, Howard; Mohri, Hiroshi

doi:10.1097/qai.0000000000001534

Cited by 61 publications

(61 citation statements)

References 22 publications

(21 reference statements)

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“…TDF/emtricitabine PrEP is not fail-safe, and seroconversion despite excellent adherence has been reported in cases of high inoculum or viral resistance. 142,144,145 …”

Section: Preventionmentioning

confidence: 99%

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Saag

Benson

Gandhi

et al. 2018

JAMA

514

287

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IMPORTANCE Antiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection. OBJECTIVE To evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk. EVIDENCE REVIEW New evidence collected since the International Antiviral Society–USA 2016 recommendations via monthly PubMed and EMBASE literature searches up to April 2018; data presented at peer-reviewed scientific conferences. A volunteer panel of experts in HIV research and patient care considered these data and updated previous recommendations. FINDINGS ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV. CONCLUSIONS AND RELEVANCE Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.

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“…TDF/emtricitabine PrEP is not fail-safe, and seroconversion despite excellent adherence has been reported in cases of high inoculum or viral resistance. 142,144,145 …”

Section: Preventionmentioning

confidence: 99%

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Saag

Benson

Gandhi

et al. 2018

JAMA

514

287

View full text Add to dashboard Cite

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“…Currently, DBS are being collected to quantify adherence in various studies evaluating novel PrEP formulations and drug delivery strategies (NCT02720094, NCT03164564, NCT02842086) in the US and around the world. In addition, DBS sampling has been frequently performed in cases of PrEP breakthrough to determine the role of drug adherence[56–58]. …”

Section: New Pharmacologic Measures That Quantify Cumulative Drug Expmentioning

confidence: 99%

Adherence Measurements in HIV: New Advancements in Pharmacologic Methods and Real-Time Monitoring

2018

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Antiretroviral drug concentrations in hair and dried blood spots are two novel pharmacological measures of cumulative drug adherence and exposure that have been recently evaluated in HIV treatment and pre-exposure prophylaxis. Real-time adherence monitoring using electronic devices has also proven highly informative, feasible, and well accepted, offering the possibility for an immediate intervention when non-adherence is detected. Both approaches offer considerable advantages over traditional adherence measures in predicting efficacy. New methods to objectively monitor adherence in real-time and over long time periods have been developed. Further research is required to better understand how these measures can optimize adherence and, ultimately, improve clinical outcomes in HIV treatment and prevention.

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“…Clinicians should then switch treatment. Delaying treatment switching leads to accumulation of resistance mutations [3][4][5], unfavourable patient outcomes and increased risk of transmission of drug-resistant strains [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. If the second consecutive VL is re-suppressed, patients usually remain on the same treatment regimen assuming that treatment adherence is restored without major drug resistance (DR).…”

Section: Introductionmentioning

confidence: 99%

Successes and challenges in optimizing the viral load cascade to improve antiretroviral therapy adherence and rationalize second‐line switches in Swaziland

et al. 2018

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IntroductionAs antiretroviral therapy (ART) is scaled up, more patients become eligible for routine viral load (VL) monitoring, the most important tool for monitoring ART efficacy. For HIV programmes to become effective, leakages along the VL cascade need to be minimized and treatment switching needs to be optimized. However, many HIV programmes in resource‐constrained settings report significant shortfalls.MethodsFrom a public sector HIV programme in rural Swaziland, we evaluated the VL cascade of adults (≥18 years) on ART from the time of the first elevated VL (>1000 copies/mL) between January 2013 and June 2014 to treatment switching by December 2015. We additionally described HIV drug resistance for patients with virological failure. We used descriptive statistics and Kaplan–Meier estimates to describe the different steps along the cascade and regression models to determine factors associated with outcomes.Results and DiscussionOf 828 patients with a first elevated VL, 252 (30.4%) did not receive any enhanced adherence counselling (EAC). Six hundred and ninety‐six (84.1%) patients had a follow‐up VL measurement, and the predictors of receiving a follow‐up VL were being a second‐line patient (adjusted hazard ratio (aHR): 0.72; p = 0.051), Hlathikhulu health zone (aHR: 0.79; p = 0.013) and having received two EAC sessions (aHR: 1.31; p = 0.023). Four hundred and ten patients (58.9%) achieved VL re‐suppression. Predictors of re‐suppression were age 50 to 64 (adjusted odds ratio (aOR): 2.02; p = 0.015) compared with age 18 to 34 years, being on second‐line treatment (aOR: 3.29; p = 0.003) and two (aOR: 1.66; p = 0.045) or three (aOR: 1.86; p = 0.003) EAC sessions. Of 278 patients eligible to switch to second‐line therapy, 120 (43.2%) had switched by the end of the study. Finally, of 155 successfully sequenced dried blood spots, 144 (92.9%) were from first‐line patients. Of these, 133 (positive predictive value: 92.4%) had resistance patterns that necessitated treatment switching.ConclusionsPatients on ART with high VLs were more likely to re‐suppress if they received EAC. Failure to re‐suppress after counselling was predictive of genotypically confirmed resistance patterns requiring treatment switching. Delays in switching were significant despite the ability of the WHO algorithm to predict treatment failure. Despite significant progress in recent years, enhanced focus on quality care along the VL cascade in resource‐limited settings is crucial.

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Newly Acquired Infection With Multidrug-Resistant HIV-1 in a Patient Adherent to Preexposure Prophylaxis

Cited by 61 publications

References 22 publications

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Adherence Measurements in HIV: New Advancements in Pharmacologic Methods and Real-Time Monitoring

Successes and challenges in optimizing the viral load cascade to improve antiretroviral therapy adherence and rationalize second‐line switches in Swaziland

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