The risks and benefits of structured treatment interruption (STI) in HIV-1-infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subjects with HIV-1 plasma RNA levels (VL) <400 copies per ml and CD4 ؉ T cells >400 per l. CD4 ؉ T cells, VL, HIV-1-specific neutralizing antibodies, and IFN-␥-producing HIV-1-specific CD8 ؉ and CD4 ؉ T cells were measured in all subjects. STIs of 1-month duration separated by 1 month of HAART, before a final 3-month STI, resulted in augmented CD8 ؉ T cell responses in all eight STI subjects (P ؍ 0.003), maintained while on HAART up to 22 weeks after STI, and augmented neutralization titers to autologous HIV-1 isolate in one of eight subjects. However, significant decline of CD4 ؉ T cell count from pre-STI level, and VL rebound to pre-HAART baseline, occurred during STI (P ؍ 0.001 and 0.34, respectively). CD4 ؉ T cell counts were regained on return to HAART. Control subjects (n ؍ 4) maintained VL <400 copies per ml and stable CD4 ؉ T cell counts, and showed no enhancement of antiviral CD8 ؉ T cell responses. Despite increases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution.
The models suggest that structured therapy interruption only leads to transient or sustained virus control if the immune effector cells increase during therapy. This increase must more than counterbalance the increase in susceptible target cells induced by therapy. The risk of inducing drug resistance by therapy interruptions or the risk of repopulating the pool of latent cells during drug-free periods may be small if the virus population remains at levels considerably below baseline. However, if the virus load increases during drug-free periods to levels similar to or higher than baseline before therapy, both these risks increase dramatically.
Our findings suggest that STI in chronic HIV-1 infection might augment HIV-1-specific cellular immune responses associated with a spontaneous and sustained drop in plasma viral load in some subjects but at the potential cost of lower CD4 T-cell counts.
Immunologic and virologic outcomes of treatment interruption were compared for 5 chronically human immunodeficiency virus (HIV)-infected persons who have maintained antiretroviral therapy-mediated virus suppression, as compared with 5 untreated controls. After a median interruption of 55 days of therapy accompanied by rebound of virus, reinitiated therapy in 4 of 5 subjects resulted in suppression of 98.86% of plasma virus load by 21-33 days and no significant decrease in CD4 T cell percentage from baseline. Increased T helper responses against HIV-1 p24 antigen (P=. 014) and interferon-gamma-secreting CD8 T cell responses against HIV-1 Env (P=.004) were present during interruption of therapy and after reinitiation of treatment. The remaining subject whose treatment was interrupted did not resume treatment and continued to have a low virus load (<1080 HIV-1 RNA copies/mL) and persistent antiviral cell-mediated responses. In summary, cellular immunity against autologous HIV-1 has the potential to be acutely augmented in association with temporary treatment interruption in chronically infected persons.
Human endogenous retrovirus K (HERV-K) is distinctive among the retroviruses that comprise about 8% of the human genome in that multiple HERV-K proviruses encode full-length viral proteins, and many HERV-K proviruses formed during recent human evolution. HERV-K gag proteins are found in the cytoplasm of primary tumor cells of patients with seminoma. We identified HERV-K-specific T cells in patients with a past history of seminoma using the interferon-gamma ELISPOT assay and an MHC-HERV-K peptide-specific tetramer. A minority of apparently healthy subjects without evident germ cell tumors also made HERV-K-specific T cell responses. In summary, we detected T cell reactivity to HERV-K peptides in both past seminoma patients and a minority of apparently healthy controls.
IMPORTANCETransgender is an umbrella term used to describe individuals whose gender identity and/or gender expression differs from assigned sex at birth. There are an estimated 1.4 million transgender adults in the United States, and this number is increasing. Clinicians will increasingly be caring for transgender patients. Topics considered in this narrative review include terminology, how to address transgender patients, obtaining an inclusive history that takes into account gender-affirming surgery, managing hormone therapy and other clinical issues, consideration for hospitalized patients, interpreting laboratory values in the setting of hormone use, legal issues, and considerations for health systems.OBSERVATIONS Best practices in caring for a transgender patient include using a patient-identified name and pronoun, using gender-neutral terminology until the appropriate term is identified by the patient, and obtaining a surgical history inclusive of an anatomic inventory. Gender-affirming hormones can modify disease-specific risk factors or confer risk for in-hospital complications. They can also cause changes in laboratory values; however, studies are limited to observational studies and case series. Some data are derived and extrapolated from cisgender populations. There are also unique systems-based concerns, including lack of procedures for standardized collection of gender identity and lack of sufficiently comprehensive electronic health record platforms. Vulnerabilities exist for hospitalized transgender patients in the transition from the inpatient to outpatient care that require dedicated institutional efforts to address.
CONCLUSIONS AND RELEVANCEClinicians should learn how to engage with transgender patients, appreciate that unique anatomy or the use of gender-affirming hormones may affect the prevalence of certain disease (eg, cardiovascular disease, venous thromboembolism, and osteoporosis), and be prepared to manage specific issues, including those related to hormone therapy. Health care facilities should work toward providing inclusive systems of care that correctly identify and integrate information about transgender patients into the electronic health record, account for the unique needs of these patients within the facility, and through education and policy create a welcoming environment for their care.
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