Kara S. McGee

Antiretroviral therapy initiated during acute HIV infection fails to prevent persistent T-cell activation.

Abstract:Initiation of antiretroviral therapy during acute HIV-1 infection may prevent persistent immune activation. We analyzed longitudinal CD38+HLA-DR+ CD8+ T-cell percentages in 31 acutely infected individuals who started early (median 43 days since infection) and successful antiretroviral therapy, and maintained viral suppression through 96 weeks. Pretherapy a median of 72.6% CD8+ T cells were CD38+HLA-DR+, and although this decreased to 15.6% by 96 weeks, it remained substantially higher than seronegative controls (median 8.9%, P = 0.008). Shorter time to suppression predicted lower activation at 96 weeks. These results support the hypothesis that very early events in HIV-1 pathogenesis may result in prolonged immune dysfunction.

CD4+CD8+ T Cells Represent a Significant Portion of the Anti-HIV T Cell Response to Acute HIV Infection

Previous studies have revealed that HIV-infected individuals possess circulating CD4+CD8+ double-positive (DP) T cells specific for HIV Ags. In the present study, we analyzed the proliferation and functional profile of circulating DP T cells from 30 acutely HIV-infected individuals and 10 chronically HIV-infected viral controllers. The acutely infected group had DP T cells that showed more proliferative capability and multifunctionality than did both their CD4+ and CD8+ T cells. DP T cells were found to exhibit greater proliferation and higher multifunctionality compared with CD4 T cells in the viral controller group. The DP T cell response represented 16% of the total anti-HIV proliferative response and >70% of the anti-HIV multifunctional response in the acutely infected subjects. Proliferating DP T cells of the acutely infected subjects responded to all HIV Ag pools with equal magnitude. Conversely, the multifunctional response was focused on the pool representing Nef, Rev, Tat, VPR, and VPU. Meanwhile, the controllers’ DP T cells focused on Gag and the Nef, Rev, Tat, VPR, and VPU pool for both their proliferative and multifunctional responses. Finally, we show that the presence of proliferating DP T cells following all HIV Ag stimulations is well correlated with proliferating CD4 T cells whereas multifunctionality appears to be largely independent of multifunctionality in other T cell compartments. Therefore, DP T cells represent a highly reactive cell population during acute HIV infection, which responds independently from the traditional T cell compartments.

Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection.

Objective:Characterize responses to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral treatment (ART) initiated during acute HIV infection (AHI). Design:This was a prospective, single-arm evaluation of once-daily, co-formulated emtricitabine/tenofovir/efavirenz initiated during AHI. Methods:The primary endpoint is the proportion of responders with HIV RNA less than 200 copies/ml by week 24. We examined time to viral suppression and CD8 cell activation in relation to baseline participant characteristics. We compared time to viral suppression and viral dynamics using linear mixed-effects models between acutely infected participants and chronically infected controls. Results:Between January 2005 and May 2009, 61 AHI participants were enrolled. Of participants whose enrollment date allowed 24 and 48 weeks of follow-up, 47 of 51 (92%) achieved viral suppression to less than 200 copies/ml by week 24, and 35 of 41 (85.4%) to less than 50 copies/ml by week 48. The median time from ART initiation to suppression below 50 copies/ml was 93 days (range 14–337). Higher HIV RNA levels at ART initiation (P = 0.02), but not time from estimated date of infection to ART initiation (P = 0.86), were associated with longer time to viral suppression. The median baseline frequency of activated CD8+CD38+HLA-DR+ T cells was 67% (range 40–95), and was not significantly associated with longer time to viral load suppression (P = 0.15). Viremia declined to less than 50 copies/ml more rapidly in AHI than chronically infected participants. Mixed-model analysis demonstrated similar phase I HIV RNA decay rates between acute and chronically infected participants, and more rapid viral decline in acutely infected participants in phase II. Conclusion:Once-daily emtricitabine/tenofovir/efavirenz initiated during AHI achieves rapid and sustained HIV suppression during this highly infectious period.

Disability and home hazards and safety practices in US households

BACKGROUND Individuals with disabilities have an elevated risk of residential injury. However, the prevalence of home hazards and safety practices among households where an individual with a disability resides is unknown. METHODS This study examined patterns of home hazards and safety practices among 1003 households across the United States in 2002. RESULTS Households with at least 1 resident with a disability had a lower prevalence of household hazards than those without a resident with a disability, including living in a 2-story dwelling (34.6% vs 50.7%) and having stairs inside the home (48.1% vs 58.4%). They were more likely to implement fall prevention strategies, such as handrails or grab bars in the bathroom (40.4% vs 21.8%) and mats or nonskid strips in the tub or shower (71.7% vs 61.5%). CONCLUSION There is room for improvement in safety practices among households where an individual with a disability resides.

Incident sexually transmitted infection as a biomarker for high-risk sexual behavior after diagnosis of acute HIV.

Background Sexually transmitted infection (STI) diagnosis after diagnosis of acute HIV infection (AHI) indicates ongoing high-risk sexual behavior and possible risk of HIV transmission. We assessed predictors of STI acquisition and the effect of time since care entry on STI incidence in patients with AHI in care and receiving consistent risk-reduction messaging. Methods Data on incident gonorrhea, chlamydia, trichomoniasis, primary/secondary syphilis, demographic, and clinical risk factors were abstracted from medical charts for patients diagnosed as having AHI and engaged in care. Poisson regression models using generalized estimating equations were fit to estimate incidence rates (IRs), IR ratios, and robust 95% confidence intervals. Results Among 185 patients with AHI, 26 (14%) were diagnosed as having at least 1 incident STI over 709.4 person-years; 46 STIs were diagnosed during follow-up (IR, 6.8/100 person-years). The median time from HIV care entry to first STI diagnosis was 609 days (range, 168–1681 days). Men who have sex with men (P = 0.03), a shorter time between presentation to medical care and AHI diagnosis (P = 0.06), and STI diagnosis before AHI diagnosis (P = 0.0003) were predictors of incident STI. Sexually transmitted infection IR greater than 1 year after entering care was double that of patients in care 1 year or less (IR ratio, 2.0; 95% confidence interval, 0.8–4.9). HIV viral load was above the limits of detection within 1 month of 11 STI diagnoses in 6 patients (23.1%) (median, 15,898 copies/mL; range, 244–152,000 copies/mL). Conclusions Despite regular HIV care, STI incidence was high among this primarily young, men who have sex with men AHI cohort. Early antiretroviral initiation may decrease HIV transmission given ongoing risk behaviors despite risk-reduction messaging.

An educational initiative in response to identified PrEP prescribing needs among PCPs in the Southern U.S.

ABSTRACT Pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, but many primary care physicians (PCPs) have not incorporated PrEP into practice. While PrEP may be a key strategy to reducing high HIV transmission rates in the southern US, knowledge about PrEP prescribing patterns among PCPs in this region is lacking. An online survey was sent to a large network of PCPs at an academic medical center in North Carolina in October 2015. The survey was repeated in September 2016, after an educational intervention that included on-site trainings at 14 PCP offices. Chi-square tests were used to compare PrEP prescribing patterns among providers. The initial survey was sent to 389 PCPs, with 115 (30%) responding. Of these, 78% reported seeing men who have sex with men (MSM). Only 17% had prescribed PrEP. The most frequently identified barrier was lack of knowledge (60%). When the survey was repeated after the educational initiative, 79 PCPs (20%) responded. Of these, 90% reported seeing MSM, and 35% had prescribed PrEP. PCPs who had attended a training were more likely to have prescribed PrEP (OR 4.84, CI 1.77–13.21). In conclusion, PrEP prescribing among PCPs in the southern US is low. A survey among PCPs identified lack of knowledge as a barrier to prescribing, motivating an institutional-wide educational campaign in response. Further efforts are needed to continue to raise awareness and educate PCPs in the South about PrEP.

Fixed-dose combination emtricitabine/tenofovir/efavirenz initiated during acute HIV infection; 96-week efficacy and durability

Background:Updated guidelines recommend immediate antiretroviral treatment (ART) during acute HIV infection (AHI), but efficacy data on regimens during AHI are limited. Methods:We provide final data on a prospective, single-arm 96-week open-label study of once-daily emtricitabine/tenofovir/efavirenz initiated during AHI. The primary endpoint was the proportion of responders with HIV RNA less than 200 copies/ml by week 24. We examined time to viral suppression, retention, and CD8+ cell activation through week 96 in relation to baseline characteristics. Results:Between January 2005 and December 2011, 92 AHI participants enrolled. Most participants (78%) were men who have sex with men (MSM), and 42% were young MSM (18–25 years of age). Two participants withdrew leaving 90 patients for analysis. Eighty-one (90%) remained on therapy and achieved viral suppression to less than 200 copies/ml by week 24, and 71 (79%) to less than 50 copies/ml at week 48. The median time from ART initiation to suppression less than 200 copies/ml was 65 days (range 7–523) and to less than 50 copies/ml was 105 days (range 14–523). The frequency of immune activation declined from a median of 67% to 16% through week 96. Retention on study was maintained in 92% of participants at week 48 and in 83% through week 96. Among 75 participants retained through week 96, 92% were suppressed to less than 50 copies/ml. Among 39 young MSM, 79% completed a week 96 visit and 67% were suppressed at week 96. Conclusion:ART during AHI resulted in rapid and sustained viral suppression with high rates of retention in care and on ART in this cohort including a large proportion of young MSM.

Partnerships between a University-Affiliated Clinic and Community Based Organizations to Reach Black Men who have Sex with Men for PrEP Care

*Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom †Social Entrepreneurship for Sexual Health (SESH) Global, Guangzhou, China ‡Central Clinical School, Monash University, Victoria, Australia §School of Public Health, Shandong University, Jinan, China kEastern Virginia Medical School, Norfolk, VA ¶University of North Carolina at Chapel Hill, Chapel Hill, NC #Shandong Centre for Disease Control and Prevention, Jinan, China **School of Medicine, University of California, San Francisco, CA ††Guangdong Provincial Centre for Skin Disease and STI Control, Guangzhou, China ‡‡Dermatology Hospital, Southern Medical University, Guangzhou, China §§Guangdong Dermatology Hospital, Guangzhou, China kkDepartment of International Public Health, Liverpool School of Tropical Medicine, Liverpool, United Kingdom

The Development of an HIV Training Program for Nurse Practitioners.

&NA; Responding to a national need for a new workforce of HIV care providers as the first generation of providers decrease their practices or retire, the Duke University School of Nursing, with funding from the Health Resources and Services Administration, developed and implemented a program to train nurse practitioners (NP) to assume the full spectrum of primary care services needed by people living with HIV infection and various co‐morbidities. The 12‐credit program includes course work in HIV‐related epidemiology; pathogenesis; psychosocial, political, ethical, and legal issues; and pharmacology and clinical management. Students complete 392 hours of HIV‐specific clinical practice in addition to clinical hours required of all NP students. The program is the only distance‐based program of its kind in the United States. Online didactic instruction is complemented by campus‐based sessions with interprofessional faculty. We describe the 5 overarching goals that frame the program, and challenges and progress toward achieving those goals.