C. Bradley Hare

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.

Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy

Objective:To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut. Design:Open-label study in HIV-positive adults on ART with plasma HIV RNA below 40 copies/ml. Methods:Seven HIV-positive adults received 12 weeks of ART intensification with raltegravir alone or in combination with efavirenz or darunavir. Gut cells were obtained by upper and lower endoscopy with biopsies from duodenum, ileum, colon, and rectum at baseline and 12 weeks. Study outcomes included plasma HIV RNA, HIV DNA and RNA from peripheral blood mononuclear cells (PBMC) and four gut sites, T-cell subsets, and activation markers. Results:Intensification produced no consistent decrease in HIV RNA in the plasma, PBMC, duodenum, colon, or rectum. However, five of seven participants had a decrease in unspliced HIV RNA per 106 CD4+ T cells in the ileum. There was a trend towards decreased T-cell activation in all sites, which was greatest for CD8+ T cells in the ileum and PBMC, and a trend towards increased CD4+ T cells in the ileum. Conclusion:Most HIV RNA and DNA in the blood and gut is not the result of ongoing replication that can be impacted by short-term intensification with raltegravir. However, the ileum may support ongoing productive infection in some patients on ART, even if the contribution to plasma RNA is not discernible.

Differences in HIV Burden and Immune Activation within the Gut of HIV-Positive Patients Receiving Suppressive Antiretroviral Therapy

BACKGROUND The gut is a major reservoir for human immunodeficiency virus (HIV) in patients receiving antiretroviral therapy (ART). We hypothesized that distinct immune environments within the gut may support varying levels of HIV. METHODS In 8 HIV-1-positive adults who were receiving ART and had CD4(+) T cell counts of >200 cells/μL and plasma viral loads of <40 copies/mL, levels of HIV and T cell activation were measured in blood samples and endoscopic biopsy specimens from the duodenum, ileum, ascending colon, and rectum. RESULTS HIV DNA and RNA levels per CD4(+) T cell were higher in all 4 gut sites compared with those in the blood. HIV DNA levels increased from the duodenum to the rectum, whereas the median HIV RNA level peaked in the ileum. HIV DNA levels correlated positively with T cell activation markers in peripheral blood mononuclear cells (PBMCs) but negatively with T cell activation markers in the gut. Multiply spliced RNA was infrequently detected in gut, and ratios of unspliced RNA to DNA were lower in the colon and rectum than in PBMCs, which reflects paradoxically low HIV transcription, given the higher level of T cell activation in the gut. CONCLUSIONS HIV DNA and RNA are both concentrated in the gut, but the inverse relationship between HIV DNA levels and T cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00884793 (PLUS1).

The Setpoint Study (ACTG A5217): Effect of Immediate Versus Deferred Antiretroviral Therapy on Virologic Set Point in Recently HIV-1–Infected Individuals

BACKGROUND The benefits of antiretroviral therapy during early human immunodeficiency virus type 1 (HIV-1) infection remain unproved. METHODS A5217 study team randomized patients within 6 months of HIV-1 seroconversion to receive either 36 weeks of antiretrovirals (immediate treatment [IT]) or no treatment (deferred treatment [DT]). Patients were to start or restart antiretroviral therapy if they met predefined criteria. The primary end point was a composite of requiring treatment or retreatment and the log(10) HIV-1 RNA level at week 72 (both groups) and 36 (DT group). RESULTS At the June 2009 Data Safety Monitoring Board (DSMB) review, 130 of 150 targeted participants had enrolled. Efficacy analysis included 79 individuals randomized ≥72 weeks previously. For the primary end point, the IT group at week 72 had a better outcome than the DT group at week 72 (P = .005) and the DT group at week 36 (P = .002). The differences were primarily due to the higher rate of progression to needing treatment in the DT group (50%) versus the IT (10%) group. The DSMB recommended stopping the study because further follow-up was unlikely to change these findings. CONCLUSIONS Progression to meeting criteria for antiretroviral initiation in the DT group occurred more frequently than anticipated, limiting the ability to evaluate virologic set point. Antiretrovirals during early HIV-1 infection modestly delayed the need for subsequent treatment. CLINICAL TRIALS REGISTRATION NCT00090779.

Simvastatin-Nelfinavir Interaction Implicated in Rhabdomyolysis and Death

We report the first death associated with rhabdomyolysis in a patient treated with a statin and a protease inhibitor, which produced a significant drug-drug interaction.

Methamphetamine use, sexual activity, patient-provider communication, and medication adherence among HIV-infected patients in care, San Francisco 2004-2006.

Abstract While numerous studies examine methamphetamine use and associated risky sexual behaviors in HIV-uninfected individuals, few studies have surveyed HIV-infected individuals in the health care setting. To assess the frequency and trends of methamphetamine use, sexual activity, injection drug use, patient–provider communication, and medication adherence among HIV-infected persons in care, we administered a one-page anonymous survey in 2004 and 2006. The survey was conducted at the two University of California, San Francisco outpatient HIV clinics: at Moffitt Hospital (Moffitt), serving primarily privately insured patients, and at San Francisco General Hospital (SFGH), a county hospital serving primarily patients who are uninsured or publicly insured. In 2006, 39% of men who have sex with men (MSM), 33% of heterosexual men, and 11% of women reported methamphetamine use in the prior 12 months. Methamphetamine use was significantly associated with an increased number of sex partners among MSM and heterosexual men, and poor anti-retroviral medication adherence. Among MSM, methamphetamine use was more common at the SFGH clinic. Between 2004 and 2006, reported methamphetamine use in the last 12 months decreased among MSM at Moffitt (38 to 20%, p<0.01), but increased at SFGH (40 to 50%, p<0.05). Among methamphetamine users we found a high frequency of injection of methamphetamine, which increased at SFGH from 38 to 55%, p<0.05. Patient–provider communication regarding methamphetamine use has increased from 2004 to 2006 but no significant change has been found for providers asking patients about sexual activity. Overall, we found methamphetamine use to be common among HIV-infected patients in care, and associated with an increased number of sex partners, a high frequency of injection drug use, and poor adherence to anti-retroviral medications. These findings support the need for improved screening and clinic-based interventions to reduce and treat methamphetamine abuse and associated high risk sexual behaviors.

Personal health records in a public hospital: experience at the HIV/AIDS clinic at San Francisco General Hospital

Personal health records (PHRs) are information repositories; however, PHRs may be less available to persons in the safety net setting. We deployed a free, secure, internet-based PHR for persons receiving care at the AIDS/HIV clinic at San Francisco General Hospital. In our initial rollout, 221 persons registered for the PHR. Compared to the entire clinic, these initial users were more likely to be Caucasian, male, non-Hispanic, on antiretroviral medications, and have better control of their HIV infection. The median number of online sessions was 7 and the median session length was 4 min. Laboratory results were the most commonly accessed feature. Patients were satisfied with the PHR and more than 80% of users agreed that the PHR helped them manage their medical problems; however, some users were concerned that their health information was not accurate or secure. Patients in a safety net setting will access and use an online PHR.

Simplifying Consent for HIV Testing Is Associated with an Increase in HIV Testing and Case Detection in Highest Risk Groups, San Francisco January 2003–June 2007

Background Populations at highest risk for HIV infection face multiple barriers to HIV testing. To facilitate HIV testing procedures, the San Francisco General Hospital Medical Center eliminated required written patient consent for HIV testing in its medical settings in May 2006. To describe the change in HIV testing rates in different hospital settings and populations after the change in HIV testing policy in the SFDH medical center, we performed an observational study using interrupted time series analysis. Methods Data from all patients aged 18 years and older seen from January 2003 through June 2007 at the San Francisco Department of Public Health (SFDPH) medical care system were included in the analysis. The monthly HIV testing rate per 1000 hadpatient-visits was calculated for the overall population and stratified by hospital setting, age, sex, race/ethnicity, homelessness status, insurance status and primary language. Results By June 2007, the average monthly rate of HIV tests per 1000 patient-visits increased 4.38 (CI, 2.17–6.60, p<0.001) over the number predicted if the policy change had not occurred (representing a 44% increase). The monthly average number of new positive HIV tests increased from 8.9 (CI, 6.3–11.5) to 14.9 (CI, 10.6–19.2, p<0.001), representing a 67% increase. Although increases in HIV testing were seen in all populations, populations at highest risk for HIV infection, particularly men, the homeless, and the uninsured experienced the highest increases in monthly HIV testing rates after the policy change. Conclusions The elimination of the requirement for written consent in May 2006 was associated with a significant and sustained increase in HIV testing rates and HIV case detection in the SFDPH medical center. Populations facing the higher barriers to HIV testing had the highest increases in HIV testing rates and case detection in response to the policy change.

Detection of Nonnucleoside Reverse-Transcriptase Inhibitor-Resistant HIV-1 after Discontinuation of Virologically Suppressive Antiretroviral Therapy

Using standard and ultrasensitive techniques, we detected nonnucleoside reverse-transcriptase inhibitor-associated resistance mutations in 11 (20%) of 54 subjects who discontinued virologically suppressive nonnucleoside reverse-transcriptase inhibitor-containing antiretroviral therapy. Resistance was detected in 45% and 14% of subjects with a baseline human immunodeficiency virus type 1 RNA level of 51-400 copies/mL and <or=50 copies/mL, respectively. Mutations remained detectable for at least 48 weeks in some subjects.

Testing and Linkage to Care Outcomes for a Clinician-Initiated Rapid HIV Testing Program in an Urban Emergency Department

The urban emergency department is an important site for the detection of HIV infection. Current research has focused on strategies to increase HIV testing in the emergency department. As more emergency department HIV cases are identified, there need to be well-defined systems for linkage to care. We conducted a retrospective study of rapid HIV testing in an urban public emergency department and level I trauma center from June 1, 2008, to March 31, 2010. The objectives of this study were to evaluate the increase in the number of tests and new HIV diagnoses resulting from the addition of targeted testing to clinician-initiated diagnostic testing, describe the demographic and clinical characteristics of patients with newly diagnosed HIV infection, and assess the effectiveness of an HIV clinic based linkage to care team. Of 96,711 emergency department visits, there were 5340 (5.5%) rapid HIV tests performed, representing 4827 (91.3%) unique testers, of whom 62.4% were male and 60.8% were from racial/ethnic minority groups. After the change in testing strategy, the median number of tests per month increased from 114 to 273 (p=0.004), and the median number of new diagnoses per month increased from 1.5 to 4 (p=0.01). From all tests conducted, there were 65 new diagnoses of HIV infection (1.2%, 95% confidence interval [CI] 0.9%, 1.5%). The linkage team connected over 90% of newly diagnosed and out-of-care HIV-infected patients to care. In summary, the addition of targeted testing to diagnostic testing increased new HIV case identification, and an HIV clinic-based team was effective at linkage to care.