HIV Infection and Drug Resistance with Unsupervised Use of HIV Pre-Exposure Prophylaxis.

Although the Centers for Disease Control and Prevention currently only recommend daily dosing of HIV pre-exposure prophylaxis (PrEP), an on-demand PrEP dosing strategy that includes doses before and after sexual activity has been shown to reduce risk for HIV acquisition in men who have sex with men. In this letter, we report a case of HIV infection and drug resistance in a patient using PrEP outside of regular clinical care, adopting a sporadic, suboptimal dosing strategy with pills he obtained from his sexual partners. This case illustrates the potential risks of PrEP use without provider monitoring to ensure safe and effective dosing and laboratory follow-up, as well as key challenges that must be addressed as nondaily PrEP use becomes more common outside of controlled research settings.

Preexposure Prophylaxis for HIV Prevention in a Large Integrated Health Care System: Adherence, Renal Safety, and Discontinuation.

BACKGROUND: Placebo-controlled and open-label studies have demonstrated the safety and efficacy of daily oral preexposure prophylaxis (PrEP) in preventing HIV infection, but data are limited on real-world PrEP use. METHODS: We conducted a cohort study from July 2012 through June 2015 of Kaiser Permanente Northern California members initiating PrEP. We assessed pharmacy refill adherence and discontinuation, decreases in estimated glomerular filtration rate (eGFR), and sexually transmitted infection (STI)/HIV incidence. RESULTS: Overall, 972 individuals initiated PrEP, accumulating 850 person-years of PrEP use. Mean adherence was 92% overall. Black race/ethnicity [adjusted risk ratio (aRR) 3.0; 95% confidence interval: 1.7 to 5.1, P < 0.001], higher copayments (aRR 2.0; 1.2 to 3.3, P = 0.005), and smoking (aRR 1.6; 1.1 to 2.3, P = 0.025) were associated with <80% adherence. PrEP was discontinued by 219 (22.5%); female sex (aRR 2.6; 1.5 to 4.6, P < 0.001) and drug/alcohol abuse (aRR 1.8; 1.3 to 2.6, P = 0.002) were associated with discontinuation. Among 909 with follow-up creatinine testing, 141 (15.5%) had an eGFR <70 mL·min·1.73 m and 5 (0.6%) stopped PrEP because of low eGFR. Quarterly STI positivity was high and increased over time for rectal chlamydia (P < 0.001) and urethral gonorrhea (P = 0.012). No HIV seroconversions occurred during PrEP use; however, 2 occurred in individuals who discontinued PrEP after losing insurance coverage. CONCLUSIONS: PrEP adherence was high in clinical practice, consistent with the lack of HIV seroconversions during PrEP use. Discontinuation because of renal toxicity was rare. STI screening every 6 months, as recommended by current guidelines, may be inadequate. Strategies are needed to increase PrEP access during gaps in insurance coverage.

No New HIV Infections With Increasing Use of HIV Preexposure Prophylaxis in a Clinical Practice Setting.

Referrals for and initiation of preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection increased dramatically in a large clinical practice setting since 2012. Despite high rates of sexually transmitted infections among PrEP users and reported decreases in condom use in a subset, there were no new HIV infections in this population.

Medication error in the care of HIV/AIDS patients: electronic surveillance, confirmation, and adverse events.

BACKGROUND: Medication error occurring during the care of HIV-infected patients may lead to treatment failure, drug toxicity, or even death. OBJECTIVE: The objective of this study was to ascertain and confirm 5 categories of medication error in the care of HIV-infected patients. RESEARCH DESIGN: This study was a retrospective study to describe the occurrence of preventable medication error and to determine if adverse events were associated with confirmed errors. A roster of medications for each category of potential errors was created. Computerized pharmacy records were scanned for all dispensing of these medications. Potential errors were confirmed by medical records abstraction. For the incorrect dosing, coadministration of contraindicated medications, and antiretroviral monotherapy error categories, random samples were chart reviewed for confirmation. For the remaining 2 error categories, all potential errors were chart reviewed. The positive predictive value (PPV) of potential errors, the incidence of confirmed error among all new prescription orders filled and the patient characteristics predicting likelihood of error confirmation were estimated for each error category. SUBJECTS: The study sample involved 5473 HIV-infected patients of the Kaiser Permanente Northern California (KPNC) health plan. RESULTS: Among the 5 error categories, PPVs ranged from a high of 80% for coadministration of contraindicated medications to <1% for antiretroviral monotherapy. Incidence of confirmed errors was 9.80 errors per 1000 new prescriptions dispensed for incorrect dosing, 9.51 errors per 1000 for contraindicated medications, and <1.00 for all other categories. Adverse events associated with confirmed errors were observed only in the contraindicated medications error category. The likelihood of a contraindicated medications error was significantly increased among patients >or=50 years of age and decreased among black patients. CONCLUSIONS: Use of electronic pharmacy records to ascertain true medication errors appears most reliable when conducting surveillance for contraindicated medications errors and less reliable for other error categories. Lack of confirmation is likely the result of patients' lack of adherence to drug regimens or providers' intentional deviation from accepted prescribing guidelines. Only confirmed contraindicated medications errors appear to be linked to adverse events.

HIV-1 Protease and reverse-transcriptase mutations: correlations with antiretroviral therapy in subtype B isolates and implications for drug-resistance surveillance.

Background. It is important, for drug-resistance surveillance, to identify human immunodeficiency virus type 1 (HIV-1) strains that have undergone antiretroviral drug selection.Methods. We compared the prevalence of protease and reverse-transcriptase (RT) mutations in HIV-1 sequences from persons with and without previous treatment with protease inhibitors (PIs), nucleoside RT inhibitors (NRTIs), and nonnucleoside RT inhibitors (NNRTIs). Treatment-associated mutations in protease isolates from 5867 persons and RT isolates from 6247 persons were categorized by whether they were polymorphic (prevalence, >0.5%) in untreated individuals and whether they were established drug-resistance mutations. New methods were introduced to minimize misclassification from transmitted resistance, population stratification, sequencing artifacts, and multiple hypothesis testing.Results. Some 36 established and 24 additional nonpolymorphic protease mutations at 34 positions were related to PI treatment, 21 established and 22 additional nonpolymorphic RT mutations at 24 positions with NRTI treatment, and 15 established and 11 additional nonpolymorphic RT mutations at 15 positions with NNRTI treatment. In addition, 11 PI-associated and 1 NRTI-associated established mutations were polymorphic in viruses from untreated persons.Conclusions. Established drug-resistance mutations encompass only a subset of treatment-associated mutations; some of these are polymorphic in untreated persons. In contrast, nonpolymorphic treatment-associated mutations may be more sensitive and specific markers of transmitted HIV-1 drug resistance.

Evolution of resistance to drugs in HIV-1-infected patients failing antiretroviral therapy.

BACKGROUND AND OBJECTIVE: The optimal time for changing failing antiretroviral therapy (ART) is not known. It involves balancing the risk of exhausting future treatment options against the risk of developing increased drug resistance. The frequency with which new drug-resistance mutations (DRM) developed and their potential consequences in patients continuing unchanged treatment despite persistent viremia were assessed. DESIGN: A retrospective study of consecutive sequence samples from 106 patients at one institution with viral load (VL) of more than 400 copies/ml, with no change in ART for more than 2 months despite virologic failure. METHODS: Two consecutive pol sequences, CD4 cell counts and VL were analyzed to quantify the development of new DRM and to identify changes in immunologic and virologic parameters. Genotypic susceptibility scores (GSS) and viral drug susceptibilities were calculated by a computer program (HIVDB). Poisson log-linear regression models were used to predict the expected number of mutations at the second time point. RESULTS: : After a median of 14 months of continued ART, 75% (80 of 106) of patients acquired new DRM and were assigned a significantly lower GSS, potentially limiting the success of future ART. The development of new DRM was proportional to the time between the two sequences and inversely proportional to the number of DRM in the first sequence. However, the development of DRM was not associated with significant changes in CD4 or VL counts. CONCLUSIONS: Despite stable levels of CD4 and VL over time, maintaining a failing therapeutic regimen increases drug resistance and may limit future treatment options.