Charles B. Hicks

Treatment of Syphilis: A Systematic Review

IMPORTANCEnThe incidence of syphilis in the United States is increasing; it is estimated that more than 55,000 new infections will occur in 2014. Treatment regimens are controversial, especially in specific populations, and assessing treatment response based on serology remains a challenge.nnnOBJECTIVEnTo review evidence regarding penicillin and nonpenicillin regimens, implications of the serofast state, and treatment of specific populations including those with neurosyphilis or human immunodeficiency virus (HIV) infection and pregnant women.nnnEVIDENCE REVIEWnWe searched MEDLINE for English-language human treatment studies dating from January 1965 until July 2014. The American Heart Association classification system was used to rate quality of evidence.nnnFINDINGSnWe included 102 articles in our review, consisting of randomized trials, meta-analyses, and cohort studies. Case reports and small series were excluded unless they were the only studies providing evidence for a specific treatment strategy. We included 11 randomized trials. Evidence regarding penicillin and nonpenicillin regimens was reviewed from studies involving 11,102 patients. Data on the treatment of early syphilis support the use of a single intramuscular injection of 2.4 million U of benzathine penicillin G, with studies reporting 90% to 100% treatment success rates. The value of multiple-dose treatment of early syphilis is uncertain, especially in HIV-infected individuals. Less evidence is available regarding therapy for late and late latent syphilis. Following treatment, nontreponemal serologic titers should decline in a stable pattern, but a significant proportion of patients may remain seropositive (the serofast state). Serologic response to treatment should be evident by 6 months in early syphilis but is generally slower (12-24 months) for latent syphilis. Evidence defining treatment for HIV-infected persons and for pregnant women is limited, but available data support penicillin as first-line therapy.nnnCONCLUSIONS AND RELEVANCEnThe mainstay of syphilis treatment is parenteral penicillin G despite the relatively modest clinical trial data that support its use.

History of AIDS in HIV-Infected Patients Is Associated With Higher In-Hospital Mortality Following Admission for Acute Myocardial Infarction and Stroke

BACKGROUNDnAlthough human immunodeficiency virus (HIV)-infected persons are at increased risk for major cardiovascular events, short-term prognosis after these events is unclear.nnnMETHODSnTo determine the association between HIV infection and acute myocardial infarction (AMI) and stroke outcomes, we analyzed hospital discharge data from the Nationwide Inpatient Sample (NIS) between 2002 and 2012. Multivariable logistic regression was used to evaluate the association between HIV infection and in-hospital death after AMI or stroke.nnnRESULTSnOverall, 18 369 785 AMI/stroke hospitalizations were included in the analysis. Patients with a history of AIDS were significantly more likely than uninfected patients to die during hospitalization after admission for AMI or stroke (odds ratio, 3.03 [95% confidence interval {CI}, 1.71-5.38] for AMI and 2.59 [95% CI, 1.97-3.41] for stroke). Additionally, patients with AIDS were more likely than HIV-uninfected patients to be discharged to nonhospital inpatient facilities after admission for AMI (OR, 3.14 [95% CI, 1.72-5.74]) or stroke (OR, 1.45; 95% CI, 1.12-1.87). There was a minimal difference in either outcome between HIV-infected patients without a history of AIDS and uninfected patients.nnnCONCLUSIONSnPatients with a history of AIDS were significantly more likely than uninfected patients to die during hospitalization after admission for AMI or stroke. This disparity was not observed when infected patients without a history of AIDS were compared to uninfected patients, implying that preserving immune function may improve cardiovascular outcomes in HIV-infected persons.

Syphilis on the Rise: What Went Wrong?

As the 1990s ended, syphilis was on the decline. At least in part due to safer sexual behaviors prompted by the AIDS epidemic,1 the rate of incident syphilis declined to fewer than 4 cases per 100 000 by the year 2000, a historic nadir. Eradication of Treponema pallidum infection in the United States seemed quite possible through concentrated public health efforts in a relatively small number of high-incidence US communities, and the Centers for Disease Control and Prevention (CDC) was developing a national syphilis elimination plan.2 Timing seemed auspicious for eradication efforts to be successful. Now, in 2016, hopes for eradication have long since faded, as have many of the gains realized by the effort. Rates of syphilis have trended steadily upward since 2000, and the CDC’s syphilis elimination efforts officially ended as of December 2013.

Coronary artery disease risk reduction in HIV-infected persons: a comparative analysis

ABSTRACT Despite an increased risk of coronary artery disease (CAD) in persons infected with human immunodeficiency virus (HIV), few data are available on primary prevention of CAD in this population. In this retrospective cohort study, HIV-infected patients treated in an academic medical center HIV Specialty Clinic between 1996 and 2010 were matched by age, gender, and ethnicity to a cohort of presumed uninfected persons followed in an academic medical center Internal Medicine primary care clinic. We compared CAD primary prevention care practices between the two clinics, including use of aspirin, HMG-CoA reductase inhibitors (“statins”), and anti-hypertensive drugs. CAD risk between the two groups was assessed with 10-year Framingham CAD risk scores. In the comparative analysis, 890 HIV-infected persons were compared to 807 controls. Ten-year Framingham CAD Risk Scores were similar in the two groups (median, 3; interquartile range [IQR], 0–5). After adjusting for relevant risk factors, HIV-infected persons were less likely to be prescribed aspirin (odds ratio [OR] 0.53; 95% confidence interval [CI], 0.40–0.71), statins (OR, 0.70; 95% CI, 0.53–0.92), and anti-hypertensive drugs (OR, 0.63; 95% CI, 0.50–0.79) than persons in the control group. In summary, when compared to demographically similar uninfected persons, HIV-infected persons treated in an HIV specialty clinic were less likely to be prescribed medications appropriate for CAD risk reduction. Improving primary preventative CAD care in HIV specialty clinic populations is an important step toward diminishing risk of heart disease in HIV-infected persons.

Patterns of Healthcare Utilization Among Veterans Infected With Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) and Coinfected With HIV/HCV: Unique Burdens of Disease

Background.u2003Hepatitis C virus (HCV) infection is a leading cause of cirrhosis and the primary cause of liver transplantation in the United States, and coinfection with human immunodeficiency virus (HIV) increases the risk of comorbidities. However, healthcare utilization (HCU) patterns among HIV/HCV-coinfected patients are poorly understood. This study compared the rates of HCU and reasons for hospital admission among HCV-infected, HIV-infected, and HIV/HCV-coinfected veterans. Methods.u2003Hepatitis C virus- and HIV-infected and HIV/HCV-coinfected veterans in care with the Department of Veterans Affairs (VA) from 1998 to 2009 (n = 335 371, n = 28 179, n = 13 471, respectively) were identified by HIV- and HCV-associated International Classification of Diseases, Ninth Revision codes from the clinical case registry. We assessed rates of HCU using emergency department (ED) visits, outpatient visits, and hospitalization and primary diagnoses associated with hospitalization. Independent risk factors associated with hospitalization were also examined. Results.u2003Rates of outpatient and ED visits increased over the 11-year study period for all groups, with inpatient admission rates remaining stable. The HCU rates were consistently higher for the coinfected than other cohorts. The primary reason for hospital admission for all groups was psychiatric disease/substance use, accounting for 44% of all admissions. Nadir CD4 <350 cells/mm3 was associated with higher rates of hospitalization versus nadir CD4 >500 cells/mm3. Conclusions.u2003As the current population of HCV-infected, HIV-infected, and HIV/HCV-coinfected veterans age, they will continue to place a substantial and increasing demand on the US healthcare system, particularly in their utilization of ED and outpatient services. These data suggest the need for an ongoing investment in mental health and primary care within the VA healthcare system.

The ongoing need for good physiological investigation: obstructive sleep apnea in HIV patients as a paradigm

improvements in treatment of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) have extended longevity such that >50% of those living with HIV in United States will be ≥50 yr by 2015 ([6][1]). The remarkable success of antiretroviral therapy (ART) has not been

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.

Fever and Rash in a Patient With Hepatitis

Clinical Review & Education JAMA Clinical Challenge Fever and Rash in a Patient With Hepatitis Meredith E. Clement, MD; N. Lance Okeke, MD; Charles B. Hicks, MD Figure. Left, Pigmented, macular rash on palmar surface of left hand. Right, Pigmented, macular rash on plantar surface of left foot. A 56-year-old man with longstanding human immunodeficiency vi- rus (HIV) infection presented for evaluation of new-onset fatigue and malaise. He was adherent to his antiretroviral therapy (ART) regimen (tenofovir/emtricitabine, raltegravir), with a recent CD4 lymphocyte count of 382 cells/mm 3 (18%) and HIV RNA below the level of assay detection. Initial evaluation was unremarkable except for new abnor- malities in hepatic laboratory results (alanine aminotransferase, 217 U/L (3.6 μkat/L); aspartate aminotransferase, 149 U/L (2.5 μkat/L); alka- line phosphatase, 610 U/L (10.2 μkat/L); total bilirubin, 2.2 mg/dL (37.6 μmol/L); and albumin, 3.1 g/dL). He denied having jaundice, pruritus, abdominal pain, or other gastrointestinal symptoms and re- ported no alcohol intake or recent use of new medications. He reported taking ator- Quiz at jama.com vastatin for dyslipidemia and testosterone gel for hypogonadism. Test results for hepatitis A, B, and C were nega- tive, as were results for anti–smooth muscle and antimitochondrial an- tibodies. Results of a serum antinuclear antibody test were positive, with a titer of 1:640. Liver biopsy demonstrated moderately active inter- face and lobular hepatitis with plasma cells and periportal cholestasis, findings suggestive of autoimmune hepatitis. The patient was started on prednisone and azathioprine. Shortly thereafter he developed fe- ver to 38.9°C and a macular rash that involved his palms and soles (Figure). Physical examination was otherwise normal. WHAT WOULD YOU DO NEXT? A. Stop atorvastatin secondary to statin-associated hepatitis B. Continue prednisone and azathio- prine for autoimmune hepatitis C. Check a rapid plasma reagin (RPR) test D. Biopsy the skin lesions JAMA July 28, 2015 Volume 314, Number 4 (Reprinted) Copyright 2015 American Medical Association. All rights reserved. Downloaded From: http://jama.jamanetwork.com/ by a University of California - San Diego User on 07/28/2015 jama.com

A Wake-up Call for Human Immunodeficiency Virus (HIV) Providers: Obstructive Sleep Apnea in People Living With HIV

Obstructive sleep apnea (OSA) is defined by repetitive collapse of the upper airway during sleep leading to transient hypoxemia and arousals from sleep. Surges in sympathetic activity, repeated oxygen desaturation, and sleep fragmentation can lead to cardiovascular (eg, myocardial infarction) and neurocognitive (eg, excessive daytime sleepiness) consequences. Emerging data suggest that OSA is common in people living with human immunodeficiency virus (PLWH) and that traditional risk factors for OSA, such as obesity, are not highly predictive of OSA in PLWH. Untreated OSA is associated with increased fatigue and levels of inflammation. Despite these data, most PLWH with OSA remain undiagnosed and untreated. Improved awareness of OSA among healthcare providers and greater use of OSA diagnostic approaches have the potential to substantially improve quality of life and outcomes in PLWH.

Validation of a questionnaire to monitor symptoms in HIV-infected patients during hepatitis C treatment

BackgroundClinicians are incorporating patient-reported outcomes in the management of HIV-infected persons co-infected with hepatitis C virus (HCV), but there are no validated inventories to monitor symptoms of patients during HCV therapy.DesignFive-year retrospective cohort analysis of persons living with HIV (PLWH) treated for HCV.MethodsThe HCV symptom-inventory (HCV-SI) was administered before, during, and after HCV treatment. Discriminant validity was assessed, separately, in mixed model linear regression of HCV-SI T-scores on treatment regimens (pegylated-interferon and ribavirin; pegylated-interferon, ribavirin, and telaprevir; and interferon-free antivirals); and side effect-related premature treatment discontinuation (SE-DC).ResultsFrom the 103 patients who completed the HCV-SI, 7% were female, 26% non-white, 32% cirrhotics and 91% had undetectable HIV viral loads. Most had genotype 1 (83%) and were HCV treatment-naïve (78%). We treated 19% of patients with pegylated-interferon and ribavirin, 22% with pegylated-interferon, ribavirin, and telaprevir and 59% received interferon-free antivirals. Overall, 77% achieved a sustained virologic response, and 6% discontinued HCV treatment due to side effects. In the treatment discrimination model, compared to the no treatment period, HCV-SI scores were significantly (pxa0<xa00.01) lower for interferon-free antivirals and higher for interferon-containing regimens. In the SE-DC model, the total HCV-SI, somatic and neuropsychiatric scores significantly predicted those patients who prematurely discontinued HCV treatment (Pxa0<xa00.05).ConclusionsThe HCV-SI effectively differentiated among treatment regimens known to vary by side effect profiles and between patients with and without treatment discontinuation due to side effects. The HCV-SI may have value as a patient-reported outcome instrument predicting the risk of HCV treatment discontinuation.