Overdose of the HIV Medicine Genvoya® in Two Auto-Intoxications.

Toxicological data on overdose with human immunodeficiency virus inhibitors are scarce. We present a case report of two independent suicide attempts by self-administered overdose with the same antiretroviral medicine Genvoya® (emtricitabine/elvitegravir/tenofovir alafenamide/cobicistat). Both patients were admitted to the hospital and presented with a loss of consciousness, lactic acidosis, elevated hepatic transaminase levels and hemodynamic instability. While one patient survived with advanced supportive measures, the other passed away. Emtricitabine levels were measured in vivo in various consecutive serum samples and postmortem urine, peripheral and cardiac serum samples and confirmed excessive use in both cases. This is the first time that emtricitabine levels following overdose are reported. Although measured concentrations for emtricitabine were quite similar in these cases, metabolic acidosis was more pronounced in the fatal case. The difference in outcomes between the two could be due to a difference in physiological status, susceptibility to accumulation and adverse effects, and perhaps a varying interval between ingestion and the start of supportive measures.

Genvoya-Associated and Simvastatin-Associated Noninflammatory and Nonautoimmune Myopathy: A Case Report and Literature Review.

ABSTRACT: Patients with HIV have a higher incidence of rhabdomyolysis compared with the HIV negative population because of medication-related myotoxicity and drug-drug interactions. Statins and antiretroviral therapy have been previously reported to cause myopathy in patients with HIV when used alone or in combination. In this study, we describe a case of biopsy-proven noninflammatory and nonautoimmune myopathy associated with the use of simvastatin and Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate) and review 3 previously reported similar cases. Our patient presented with acute proximal limb weakness and significantly elevated serum creatine kinase. Muscle biopsy revealed scattered degenerating and regenerating muscle fibers without evidence for an inflammatory process. She did not respond to empiric treatment with high-dose intravenous steroids and intravenous immunoglobulin. Her creatine kinase only began to downtrend after discontinuation of both simvastatin and Genvoya, and she returned to baseline function at 2-month follow-up. Our case highlights the importance of recognizing drug-drug interactions between HIV and statin medications in causing significant noninflammatory myopathy. In these patients, both categories of medications need to be discontinued for recovery.

[Case report about an initial diagnosis of HIV-infection in a young sailor through two AIDS-defining diseases with lethal progression]. / Fallbericht über die Erstdiagnose einer HIV-Erkrankung eines jungen Seemanns durch 2 AIDS-definierende Erkrankungen mit letalem Intensivverlauf.

ANAMNESIS: We saw a previously healthy 30-year-old Southeast-Asian sailor with progredient coughing and fever. EXAMINATION: We found an atypical pneumonia along with a positive HIV-test. We performed a bronchial lavage and further diagnostics for opportunistic infections. The lab work showed a viral load of 3340 000 copies/ml and a CD4-cell-count of 36/µl. DIAGNOSIS: HIV late presenter in CDC stadium C3 with Pneumocystis jirovecii and CMV pneumonia. THERAPY: We treated with Meropenem, Moxifloxacin, Cotrimoxazol, Ganciclovir and Genvoya. CLINICAL COURSE: Due to a cardio-pulmonal deterioration invasive ventilation was necessary. In the end the patient died of multi organ failure twelve days after admission despite intensive care, hemodialysis and prone positioning. CONCLUSION: This case demonstrates the difficulties in the pharmacotherapy and with drug interactions in a HIV late presenter with multi organ failure. Consultation and advice of the hospital pharmacy and the antibiotic stewardship team was vital for treating this patient. In the end cases like the portrayed should be treated in specialized clinics.

Estimated changes in price discounts for tenofovir-inclusive HIV treatments following introduction of tenofovir alafenamide.

We estimated list and net prices for tenofovir disoproxil fumarate (TDF) products Truvada, Complera, and Stribild, and their tenofovir alafenamide (TAF) versions Descovy, Odefsey, and Genvoya. Gilead offered discounts for Descovy that resulted into lower net prices compared to Truvada. This strategy encouraged patients switching from Truvada to Descovy before the availability of generic Truvada. Conversely, Gilead offered lower discounts for Odefsey and Genvoya, which resulted into higher net prices compared to Complera and Stribild.

Impact of switching to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG on cardiovascular risk and lipid profile in people living with HIV: a retrospective cohort study.

BACKGROUND: We aimed to assess the overall cardiovascular and metabolic effect of the switch to three different single tablet regimens (STRs) [tenofovir alafenamide/emtricitabine/rilpivirine (TAF/FTC/RPV), TAF/FTC/elvitegravir/cobi (TAF/FTC/EVG/cobi) and ABC/lamivudine/dolutegravir (ABC/3TC/DTG)] in a cohort of people living with HIV/AIDS (PLWH) under effective ART. METHODS: All PLWH aged above 18 years on antiretroviral treatment with an HIV-RNA < 50 cp/mL at the time of the switch to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG were retrospectively included in the analysis. Framingham risk score modification after 12 months from the switch such as lipid profile and body weight modification were assessed. The change from baseline to 12 months in mean cardiovascular risk and body weight in each of the STR's group were assessed by means of Wilcoxon signed-rank test whereas a mixed regression model was used to assess variation in lipid levels. RESULTS: Five-hundred and sixty PLWH were switched to an STR regimen of whom 170 (30.4%) to TAF/FTC/EVG/cobi, 191 (34.1%) to TAF/FTC/RPV and 199 (35.5%) to ABC/3TC/DTG. No difference in the Framingham cardiovascular risk score was observed after 12 months from the switch in each of the STR's groups. No significant overtime variation in mean total cholesterol levels from baseline to 12 months was observed for PLWH switched to ABC/3TC/DTG [200 (SD 38) mg/dl vs 201 (SD 35) mg/dl; p = 0.610] whereas a significant increment was observed in PLWH switched to TAF/FTC/EVG/cobi [192 (SD 34) mg/dl vs 208 (SD 40) mg/dl; p < 0.0001] and TAF/FTC/RPV [187 (SD 34) mg/dl vs 195 (SD 35) mg/dl; p = 0.027]. In addition, a significant variation in the mean body weight from baseline to 12 months was observed in PLWH switched to TAF/FTC/EVG/cobi [72.2 (SD 13.5) kilograms vs 74.6 (SD 14.3) kilograms; p < 0.0001] and TAF/FTC/RPV [73.4 (SD 11.6) kilograms vs 75.6 (SD 11.8) kilograms; p < 0.0001] whereas no difference was observed in those switched to ABC/3TC/DTG [71.5 (SD 12.8) kilograms vs 72.1 (SD 12.6) kilograms; p = 0.478]. CONCLUSION: No difference in the cardiovascular risk after 1 year from the switch to these STRs were observed. PLWH switched to TAF/FTC/EVG/cobi and TAF/FTC/RPV showed an increase in total cholesterol levels and body weight 12 months after the switch.

No progression of subclinical atherosclerosis in HIV-infected patients starting an initial regimen including tenofovir alafenamide/emtricitabine plus raltegravir, dolutegravir or elvitegravir/cobicistat during a two-year follow-up.

Objectives: Cardiovascular disease has become one of the most common comorbidities among HIV-infected patients, but available data about the correlation between antiretroviral drugs and progression rate of atherosclerotic disease are still limited. We evaluated the progression rate of carotid atherosclerosis in patients starting an initial antiretroviral regimen including one integrase strand transfer inhibitor (INSTI).Methods: Observational, prospective study involving HIV-1-infected, antiretroviral therapy-naive, adult patients who started an antiretroviral regimen including tenofovir alafenamide/emtricitabine (TAF/FTC) plus raltegravir (RAL group), elvitegravir/cobicistat (EVG/c group), or dolutegravir (DTG group). Patients with known cardiovascular disease or diabetes mellitus were excluded from the study. The progression rate of atherosclerosis has been assessed by carotid Doppler ultrasonography at baseline and after 24 months.Results: Overall, 102 patients were enrolled into the study: 73 males, with mean age of 48.7 years: 32, 36 and 34 patients were included in the RAL, EVG/c and DTG groups, respectively. The baseline features of the enrolled patients were comparable across the three groups. At 24 months, the mean intima-media thickness (IMT) increase at the carotid bifurcation was 0.026 mm in the RAL group, 0.029 mm in EVG/c group and 0.032 mm in DTG group. The mean IMT increases after 24 months were comparable across the three groups and statistically not significant in all the evaluated anatomical sites.Conclusions: The initial antiretroviral therapy with TAF/FTC plus RAL, EVG/c or DTG for 24 months led to a comparable and not significant effect on the progression rate of carotid atherosclerosis.

A pharmacist-led medication switch protocol in an academic HIV clinic: patient knowledge and satisfaction.

BACKGROUND: Tenofovir alafenamide (TAF) is associated with less renal and bone toxicity compared with tenofovir disoproxil (TDF). TAF's recent FDA approval has spurred HIV providers to consider switching antiretroviral therapy (ART) regimens containing TDF to TAF to minimize long term risks. Patient views on the process of such medication switches have not been explored. METHODS: Patients taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) following the Food and Drug Administration's (FDA) approval of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) received medication education from an HIV pharmacist prior to switching to the tenofovir alafenamide (TAF) formulation. Patients were asked to complete a cross-sectional survey assessing satisfaction with the switch process and knowledge about the new medication 4 to 8 weeks post-switch. RESULTS: Sixty five patients completed the switch and 57 (88%) completed a follow-up survey. Most (86%) reported understanding why the switch was made, while 91% correctly identified that TAF is associated with reduced renal toxicity, and 73% correctly identified that TAF is associated with reduced bone toxicity. No statistically significant difference was found in satisfaction with or understanding of why the medication switch was made when assessed by sex, age, race, or education, but there was a trend toward significance in the distribution of answers based on education level with those with a high school diploma, General Educational Development (GED) or less being more likely to be satisfied with the medication switch (p = 0.074). CONCLUSIONS: Education from an ambulatory clinic-based HIV pharmacist resulted in high rates of patient satisfaction and understanding of the switch from TDF to TAF-containing ART.

Development and validation of an LC-MS/MS assay for tenofovir and tenofovir alafenamide in human plasma and cerebrospinal fluid.

A liquid chromatography with triple quadrupole mass spectrometry method was developed and validated for the determination of tenofovir and tenofovir alafenamide concentrations in human plasma and cerebrospinal fluid. Tenofovir and tenofovir alafenamide were extracted from matrix by solid phase extraction. The dried extraction eluents were dissolved in water for LC-MS/MS analysis. Separation was achieved with a Phenomenex Synergi 4 µm Polar-RP 80A column (50 × 2 mm) with a gradient elution of 0.1% formic acid in water and acetonitrile. The total run time was 5 min. Detection of analytes was achieved using electrospray ionization (positive mode) and triple quadrupole selected reaction monitoring. Standard curve concentrations ranged from 0.5 to 500 ng/mL for the plasma assay and 0.1-50 ng/mL for the cerebrospinal fluid assay. The intra- and inter-day accuracy and precision were less than 12% in low, medium, and high quality control samples for both matrices. The validated methods were applied to the analysis of plasma and cerebrospinal fluid samples of a patient undergoing tenofovir therapy which involved the switch from Stribild® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) to Genvoya® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg).

A Trial of a Single-tablet Regimen of Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate for the Initial Treatment of Human Immunodeficiency Virus Type 2 Infection in a Resource-limited Setting: 48-Week Results From Senegal, West Africa.

Background: There is an urgent need for safe and effective antiretroviral therapy (ART) for human immunodeficiency virus type 2 (HIV-2) infection. We undertook the first clinical trial of a single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF) to assess its effectiveness in HIV-2-infected individuals in Senegal, West Africa. Methods: HIV-2-infected, ART-naive adults with World Health Organization stage 3-4 disease or CD4 count <750 cells/µL were eligible for this 48-week, open-label trial. We analyzed HIV-2 viral loads (VL), CD4 counts, clinical and adverse events, mortality, and loss to follow-up. Results: We enrolled 30 subjects who initiated E/C/F/TDF. Twenty-nine subjects completed 48 weeks of follow-up. The majority were female (80%). There were no deaths, no new AIDS-associated clinical events, and 1 loss to follow-up. The median baseline CD4 count was 408 (range, 34-747) cells/µL, which increased by a median 161 (range, 27-547) cells/µL at week 48. Twenty-five subjects had baseline HIV-2 VL of <50 copies/mL of plasma. In those with detectable HIV-2 VL, the median was 41 (range, 10-6135) copies/mL. Using a modified intent-to-treat analysis (US Food and Drug Administration Snapshot method), 28 of 30 (93.3%; 95% confidence interval, 77.9%-99.2%) had viral suppression at 48 weeks. The 1 subject with virologic failure had multidrug-resistant HIV-2 (reverse transcriptase mutation: K65R; integrase mutations: G140S and Q148R) detected at week 48. There were 8 grade 3-4 adverse events; none were deemed study related. Adherence and acceptability were good. Conclusions: Our data suggest that E/C/F/TDF, a once-daily, single-tablet-regimen, is safe, effective, and well tolerated. Our findings support the use of integrase inhibitor-based regimens for HIV-2 treatment. Clinical Trials Registration: NCT02180438.

Combination Therapy with Tenofovir Disoproxil Fumarate/Emtricitabine/Elvitegravir/Cobicistat Plus Darunavir Once Daily in Antiretroviral-Naive and Treatment-Experienced Patients: A Retrospective Review.

BACKGROUND: Patients with drug-resistant HIV often require complex antiretroviral regimens. However, combining fixed-dose combination tablets such as tenofovir-disoproxil-fumarate, emtricitabine, and cobicistat-boosted elvitegravir (TDF/FTC/EVG/cobi) with darunavir (DRV) can provide a simple, once-daily (QD), 2-tablet regimen for patients with drug-resistant HIV. Primary objective was to determine the percentage of patients with HIV-1 RNA <40 copies/mL at 48 weeks. METHODS: We performed a retrospective chart review of patients initiated on TDF/FTC/EVG/cobi plus DRV. RESULTS: Among the 21 included patients, prior resistance showed a median of 2 nucleoside reverse transcriptase inhibitor mutations, 1 nonnucleoside reverse transcriptase mutation, and 1 protease inhibitor mutation. At week 48, 14 (67%) patients achieved HIV-1 RNA <40 copies/mL, 1 patient experienced viral rebound, and 6 (29%) had missing data or discontinued therapy. No patient discontinued for adverse events. CONCLUSION: According to this observational study, QD TDF/FTC/EVG/cobi plus DRV is considered safe, well tolerated, and generally effective in suppressing HIV drug-resistant virus.

The informal use of antiretroviral medications for HIV prevention by men who have sex with men in South Florida: initiation, use practices, medications and motivations.

Limited data suggest that some gay and other men who have sex with men are using antiretroviral medications informally, without a prescription, for HIV prevention. This qualitative study examined this phenomenon among gay and other men who have sex with men in South Florida. Participants initiated informal antiretroviral medication use as a means of protecting each other and because of the confidence in knowledge of antiretroviral medications shared by their friends and sex partners. The most commonly used medications included Truvada and Stribild. Motivations for use included condom avoidance, risk reduction, and fear of recent HIV exposure. Participants described positive and negative sentiments related to informal use, including concerns about informal antiretroviral medications offering sufficient protection against HIV, and limited knowledge about pre-exposure prophylaxis (PrEP). Because the antiretroviral medications used for PrEP have the potential to prevent HIV infection, future research must consider the informal antiretroviral medication use and related concerns, including adherence, diversion and viral resistance.

Optimal HIV Postexposure Prophylaxis Regimen Completion With Single Tablet Daily Elvitegravir/Cobicistat/Tenofovir Disoproxil Fumarate/Emtricitabine Compared With More Frequent Dosing Regimens.

STRUCTURE: The study evaluated elvitegravir/cobicistat/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) ("Quad pill") for postexposure prophylaxis (PEP). BACKGROUND: HIV-exposed individuals may benefit from PEP, but completion rates have been suboptimal because of regimen complexity and side effects. Newer antiretroviral combinations coformulated as single daily pills may optimize PEP adherence. SETTING: One hundred HIV-uninfected individuals who presented to a Boston community health center after an acute HIV sexual exposure were enrolled and initiated PEP with the daily, single-pill combination Quad pill for a 28-day course. METHODS: Side effects and medication completion rates from study participants were compared with historical controls who had used PEP regimens consisting of TDF/FTC daily and raltegravir twice daily, or earlier regimens of twice daily zidovudine (AZT)/lamivudine (3TC) and a protease inhibitor, using χ tests for independence. RESULTS: Of the 100 participants who initiated the Quad pill for PEP after a high-risk sexual exposure, 71% completed the 28-day Quad pill regimen, which was significantly greater than historical controls who used TDF/FTC and raltegravir (57%, P < 0.05) or AZT/3TC plus a protease inhibitor (39%, P < 0.001). The most common side effects reported by Quad pill users were as follows: abdominal discomfort or pain, gas or bloating (42%), diarrhea (38%), fatigue (28%), nausea or vomiting (28%), headache (14%), or dizziness or lightheadedness (6%). Most symptoms were mild, limited, and did not result in medication discontinuation. No participants became HIV infected. CONCLUSIONS: Fixed-dose combination of elvitegravir/cobicistat/TDF/FTC was safe and well tolerated for PEP, with higher regimen completion rates than more frequently dosed PEP regimens.

Co-administration of elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine and atazanavir in treatment-experienced HIV patients.

We report the use of elvitegravir 150 mg/cobicistat 150 mg/tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (EVG/COBI/TDF/FTC) once daily, in addition to once-daily atazanavir (ATV) 300 mg, in treatment-experienced patients with human immunodeficiency virus (HIV). Due to limited data available on the co-administration of these agents, our objective was to evaluate and monitor safety and efficacy of this regimen in patients who developed resistance or intolerance to conventional antiretroviral therapy (ART). This short report included offenders incarcerated in the Illinois Department of Corrections who were ≥18 years, HIV-infected, had documented antiretroviral resistance, and received EVG/COBI/TDF/FTC + ATV once daily. Based on previous ART, resistance patterns and current medications, seven patients were initiated on once-daily therapy consisting of EVG/COBI/TDF/FTC and ATV. Due to extensive resistance, two of the seven patients were also started on abacavir (ABC) 600 mg daily in addition to EVG/COBI/TDF/FTC and ATV. Of the seven patients, one had ART changed due to concerns of resistance based on a genotype, one experienced a decline in renal function that warranted a change in therapy, and one is currently virologically suppressed on a combination of EVG/COBI/TDF/FTC, ATV, and ABC. The remaining four patients remain virologically suppressed on EVG/COBI/TDF/FTC + ATV. Therapy consisting of EVG/COBI/TDF/FTC and ATV may be a viable option for some treatment-experienced HIV-infected patients. Further studies evaluating the safety, efficacy, and pharmacokinetics of this therapy are warranted, given the lack of information currently available.

A severe hypersensitivity reaction to abacavir following re-challenge.

We report this case to highlight the possibility of a severe hypersensitivity reaction as an important potential consequence of couples, living with HIV, sharing anti-retroviral treatment. An HIV-1 positive and carrier of HLA-B*57:01 allele, treatment experienced man was commenced one pill Regimen Stribild (tenofovir, emtricitabine, elvitegravir and cobicistat) in July 2015. On running short of medication, he admitted to sharing his partner's treatment (Triumeq; abacavir, lamivudine and dolutegravir). On the second occasion, re-introduction resulted in whole body rash 4 h post dose and was associated with fever, respiratory symptoms, headache and vomiting. On examination, he was pyrexic, tachyponeic, tachycardiac and hypotensive. Hypersensitivity to abacavir can cause significant morbidity. Re-challenge can result in a more rapid, severe and potentially life-threatening reaction. This potentially could become an increasing problem with more couples, living with HIV, sharing medication.

Evaluation of tolerability with the co-formulation elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate for post-HIV exposure prophylaxis.

BACKGROUND: The preferred regimen for HIV post-exposure prophylaxis (PEP) is based mainly on safety and tolerability because it is given to immunocompetent people without HIV infection for a limited time (28 days). The frequency of adverse events (AEs) may be > 60%. Although AEs are generally not severe, they can lead to lack of adherence and failure to complete the regimen. We evaluated the co-formulation elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (Stribild®) prescribed as one pill taken once daily for HIV PEP in terms of tolerability and adherence. METHODS: This was a prospective cohort study conducted in one hospital in Paris (April to December 2015. Each participant receiving the PEP treatment (FTC-150 mg/TDF-245 mg/elvitegravir-200 mg/cobicistat 150 mg once daily) at the pharmacy of the hospital were recruited consecutively. A clinical visit was planned at 8 weeks after sexual exposure. Reminders were sent to participants who missed the appointment. A standardized questionnaire was administered to evaluate completeness and tolerability at week 8. RESULTS: Overall, 284 participants (86% men; 80% MSM; median age 30 years) were prescribed Stribild®; 50 stopped after reassessment of risk. Among 234 participants who effectively received PEP, 215 (92%) completed 28 days of PEP with only three who switched from Stribild® to another PEP because of side effects. More than 60% of participants reported at least one AE, which were mild to moderate. Fatigue, central neurological and abdominal side effects were the most frequently reported. CONCLUSIONS: Stribild® seems to be a good option for HIV PEP due to the easiness of use, the side effects profile and the high completion rate.

Safety and Tolerability of Stribild in the Southeast United States.

PURPOSE: The purpose of this study is to assess postmarketing safety and tolerability of Stribild (elvitegravir [EVG]/cobicistat [COBI]/tenofovir disoproxil fumarate [TDF]/emtricitabine [FTC]). METHODS: A retrospective, pharmacoepidemiologic study in 2 outpatient HIV clinics in the Southeast United States was conducted among adults receiving EVG/COBI/TDF/FTC. We evaluated incidence and treatment-related adverse events, including change in serum creatinine (SCr). RESULTS: Patients were primarily treatment experienced (n = 173, 60%), African American (n = 210, 73%), and males (n = 187, 65%). One hundred ninety-five (68%) patients had any increase in SCr, and 65 (23%) had an increase of ≥0.3 mg/dL. Mean SCr change from baseline to peak was 0.2 mg/dL. Being treatment experienced (odds ratio [OR] = 2.21, 95% confidence interval [CI]: 1.12-4.38) was associated with SCr ≥0.3 mg/dL, while body mass index ≥30 kg/m(2) (OR = 0.41, 95% CI: 0.18-0.93) was protective. Twenty (7%) patients discontinued therapy, 3 due to acute kidney injury. CONCLUSION: Our results demonstrate limited adverse events and low discontinuation rates associated with EVG/COBI/TDF/FTC.

Virological failure in two patients with HIV-1 RNA viral loads >1,000,000 copies/ml initiated on elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate.

Very high baseline HIV-1 RNA viral loads require potent and robust antiretroviral regimens to achieve virological suppression. The coformulated single tablet regimen of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) is recommended by the US Department of Health and Human Services for the treatment of HIV-1 in treatment-naive adults and adolescents regardless of baseline CD4(+) T-cell count and viral load. We report two cases of HIV-infected, treatment-naive patients, with baseline HIV-1 RNA viral loads >1,000,000 copies/ml who were initiated on the single tablet regimen EVG/COBI/FTC/TDF, but failed to attain viral load suppression and developed resistance to the components of EVG/COBI/FTC/TDF.