Abstract
HIV
Well-Controlled HIV Carries No Increased Mortality Risk
Based on data from two studies—the Strategies for Management of Antiretroviral Therapy (SMART) and Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT)—in which clear records were available for cause of death and clinical validation of well-controlled HIV within the previous 6 months on antiretroviral therapy (viral load ≤400 copies/mL in the SMART study and ≤500 copies/mL in the ESPRIT study), mortality rates for subjects in the control arms were compared to those in the general population. The authors concluded that non-intravenous, drug-using HIV-infected individuals who received continuous ART as part of the control treatment arms of both trials and had an undetectable viral load with maintained recovery of CD4+ T-cell counts had no increased risk of death compared to the general population. Among the 3,280 individuals followed for a total of 12,357 person-years, 62 deaths occurred, only two (3%) of which were AIDS-related. HIV-infected patients on ART who had a CD4+ T-cell count of 350–499/μL had an increased mortality rate compared to the general population, whereas there was no evidence of increased mortality for patients with CD4+ T-cell counts >500 cell/μL. The study authors noted that because the ESPRIT and SMART studies were initiated in 2000 and 2002, and patients may have been exposed to antiretroviral agents with greater toxicity than those available at present, “It is possible that patients initiating ART today have even better long-term outcomes than those observed in the ESPRIT and SMART study cohorts.”
Source: Rodger JA, Lodwick R, Mauro S, et al. Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population. AIDS 2013;27:973–979.
Antipathogenic Effects of Interferon-ε
Unlike other type 1 interferons, interferon-ε is not induced by immune cell signaling stimulated by pathogen binding. Instead, interferon-ε is continually expressed by epithelial cells in the female reproductive tract and the level of expression appears to be hormonally regulated. This type 1 cytokine is thought to help protect the female reproductive tract against viral and bacterial infections through its antipathogenic and immunoregulatory functions and may play animportant role in combating sexually transmitted diseases. Interferon-ε–deficient mice were shown to have icreased susceptibility to infection of the female reproductive tract by herpes simplex virus 2 and Chlamydia muridarum, for example.
Source: Fung KY, Mangan NE, Cumming H, et al. Infereron-ε protects the female reproductive tract from viral and bacterial infection. Science 2013;339:1088–1092.
Too Many Women in NY Get “Late” HIV Diagnosis
In the United States, more women in New York are living with HIV/AIDS than in any other state. Of the approximately 280,000 HIV-infected women nationwide, 38,840 reside in New York, according to State Health Department records. Women of color account for about 90% of the cases in New York state, and most infections were acquired as a result of heterosexual contact. About 30% of newly diagnosed women in New York receive a “late diagnosis,” defined as an initial positive HIV test result either concurrent with a diagnosis of AIDS or 12 months or less preceding an AIDS diagnosis.
Source: New York State Department of Health. Press release: National Women and Girls HIV/AIDS Awareness Day is March 10. March 8, 2013. Available at:
Exploring Mechanisms of Post-Treatment Control
“Post-treatment controllers” (PTCs) is a term used to describe HIV-infected patients in whom a prolonged regimen of combined antiretroviral therapy is initiated shortly after the primary infection and who are able to maintain HIV viremia at undetectable levels and achieve long-term virological remission after interruption of cART. Spontaneous control of viremia to undetectable levels (HIV controllers) is rare, occurring in <1% of HIV-infected patients. A study of 14 post-treatment controllers revealed mechanisms of infection control that are different at least in part than those reported in HIV controllers. Spontaneous HIV controllers tend to have an abundance of protective HLA B alleles, whereas most of the PTCs evaluated in this study had risk-associated HLA alleles that HIV-controllers do not have. The ability of PTCs to maintain viremic control is likely related to early initiation of cART, and after interruption of therapy they continue to have only a weak viral reservoir, which in some cases may even be further reduced. The authors proposed that “This might be related to the low contribution of long-lived cells to the HIV-reservoir in these patients.” They reported that few long-lived HIV-infected CD4+ T-cells were present in the total resting HIV-reservoirs in the PTCs due to a low rate of infection of naive T-cells and a skewed distribution of resting memory CD4+ T-cell subsets.
Source: Sáez-Cirión A, Bacchus C, Hocqueloux L, et al. Post-Treatment HIV-1 Controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI study. PLoS Pathog 2013;9:e1003211.
Initiating Life-Long ART in Pregnant Women Benefits Mothers and Children
Put in place by the Malawi Ministry of Health, Option B+ is a strategy for managing all HIV-infected pregnant women that involves providing life-long antiretroviral treatment regardless of a woman's CD4+ T-cell count or stage of disease. A study aimed at evaluating the cost-effectiveness of Option B+ used a decision model to simulate disease progression in a cohort of HIV-infected pregnant women who received prophylactic and antiretroviral therapy beginning in pregnancy and continued throughout life. The researchers were able to estimate the number of infections prevented in the children and the maternal life-years gained over a 10-year period, and use these data to assess the cost-effectiveness of the management strategy. The results indicated that Option B+ prevented new infant infections with a cost-effectiveness ratio of $69 per disability adjusted life-year averted, and improved the 10-year survival of mother
Source: Fasawe O, Avila C, Shaffer N, et al. Cost-effectiveness analysis of Option B+ for HIV prevention and treatment of mothers and children in Malawi. PLoS ONE 2013;8:e57778.
Problems with the Test-and-Treat Strategy
A mathematical model designed to simulate implementation of a test-and-treat policy in a population of men who have sex with men (MSM) over a 12-year period demonstrated that, while this approach offers substantial benefits, including reductions in new HIV infections, deaths, and new cases of AIDS, it would not eliminate the HIV/AIDS epidemic in MSM, and the benefits are offset by a near doubling of the prevalence of multi-drug resistance (MDR). The model developed in this study was calibrated to match HIV surveillance data from Los Angeles County during a 10-year period beginning in 2000. It was then used to simulate and predict epidemiological outcomes for a test-and-treat policy or the current strategy for the timeframe 2012–2023. Compared to the status quo, the test-and-treat scenario yielded a 34% reduction in new infection, 19% reduction in deaths, and 39% reduction in new AIDS cases by 2023. At the same time, the prevalence of MDR would increase from 4.79% to 9.06%.
Source: Sood N, Wagner Z, Jaycocks A, et al. Test and treat in Los Angeles: A mathematical model of the effects of test-and-treat for the MSM population in LA county. Clin Infect Dis 2013; doi: 10.1093/cid/cit158.
Meningitis
Meningitis Fatalities Prompt Vaccination Advisory
Within the first few weeks of 2013, four new cases of meningitis among men who have sex with men (MSM) were reported to the New York City Health Department. That brought the total number of cases to 17 since 2012 and 22 since 2010, seven of which were fatal. Of the most recent five cases, three resulted in death. A new, more lethal strain of bacterial meningitis has been identified in at least some of these cases, one that causes rapid death and, during the past couple of years, has only been seen in men who likely acquired it through anonymous sexual activity with other men, met online, for example. Earlier this year, the NYC Health Department issued new recommendations for meningitis vaccination advising men, whether or not they identify as gay, and “regardless of HIV status, who regularly have intimate contact with men met through a website digital application (“App”), or at a bar or party” to be vaccinated. A meningitis vaccine is available from hospitals, health clinics, and private physicians and it is effective against this new strain.
Sources: New York City Council. Press Release: Health Department Issues New Vaccination Recommendations for Men at Greatest Risk for Contracting Meningitis. March 6, 2013. Available at:
Hepatitis C Virus Infection
Statins Protective Against Liver Cancer
Statins may help lower the risk of hepatocellular carcinoma in individuals with chronic hepatitis C virus (HCV) infection. The authors of a population-based study of nearly 261,000 HCV-infected patients followed for 12 years reported dose–response relationship between statin use and hepatocellular carcinoma risk. Cancer developed in 3.9% of patients using statins, compared to 11.7% of those not using statins. Adjusted hazard ratios decreased from 0.66 to 0.47 and 0.33 as the statin dose range increased from 28–89 cumulative defined daily doses per year, to 90–180, and to >180, respectively, compared to patients who did not use statins. Risk of cancer also decreased in a direct duration–response relationship with statin use of at least 28 cumulative defined daily doses per year compared to nonusers.
Source: Tsan Y-T, Lee C-H, Ho W-C, et al. Statins and the risk of hepatocellular carcinoma in patients with hepatitis C virus infection. J Clin Oncol 2013; doi: 10.1200/JCO.2012.44.6831.
Well-Controlled HIV AIDS HCV Treatment in Coinfected Patients
Promising findings resulted from a study designed to evaluate the effects of sustained virologic response (SVR) in HIV-positive patients who were coinfected with hepatitis C virus (HCV) and compensated HCV-related cirrhosis, and were treated with pegylated interferon (peg-IFN) plus ribavirin (RBV). Primary outcome measures were time from the initiation of HCV therapy to evidence of hepatic decompensation and overall mortality. Of the 166 coinfected patients in the study, 25% achieved SVR. Hepatic decompensation developed in 4.6% of patients with SVR, compared to 26.8% of those without SVR. Death due to any cause occurred in 4.6% of patients with SVR and in 17.9% of patients without SVR. Factors independently associated with liver-related complications and with overall mortality were non-SVR and Model for End-Stage Liver Disease (MELD) score ≥9 at baseline.
Source: Mira JA, Rivero-Juárez A, López-Cortés LF. Benefits from sustained virologic response to pegylated interferon plus ribaviron in HIV/hepatitis C virus-coinfected patients with compensated cirrhosis. Clin Infect Dis 2013; doi: 10.1093/cid/cit103.
HIV+ HCV=More Severe Liver Disease at Younger Age
Nearly 1200 current and former intravenous drug users with antibodies to HCV who participated in the AIDS Linked to the IntraVenous Experience (ALIVE) study were evaluated for liver fibrosis and cirrhosis twice a year over a 5-year study period. About a third (34%) of the study population were coinfected with HIV and HCV. The prevalence of both clinically significant fibrosis without cirrhosis and of cirrhosis was greater in coinfected patients than in those with only HCV infection. Coinfected individuals had liver fibrosis measurements similar to those of non–HIV-infected persons who were, on average, almost 10 years older.
Source: Kirk GD, Mehta SH, Astemborski J, et al. HIV, age, and the severity of hepatitis C virus-related liver disease: A cohort study. Ann Intern Med February 26, 2013. Available at