Abstract
HIV Infection
Smoking-Related Excess Mortality Tripled Among HIV-Infected
HIV-infected individuals who are current smokers are at substantially increased risk of all-cause and non–AIDS-related mortality compared to HIV-infected nonsmokers (mortality rate ratio 4.4 and 5.3, respectively). Excess mortality per 1,000 person-years for current versus nonsmokers was 17.6 for the HIV-infected cohort compared to 4.8 for a matched HIV-negative cohort. A study that estimated life expectancies and life-years lost, in a setting in which good HIV care was available and antiretroviral therapy was free, found the HIV-infected smokers lost more life-years to smoking (12.3) than to HIV (5.1) infection, and, compared to HIV-negative individuals, excess mortality attributable to smoking is tripled and population-attributable risk of death associated with smoking is doubled. A 35-year-old HIV-infected individual who did not smoke had a median life expectancy of 78.4 years, compared to 62.6 years for the same individual who was a smoker.
Source: Helleberg M, Afzal S, Gronborg G, et al. Mortality attributable to smoking among HIV-1-infected individuals: a nationwide, population-based cohort study. Clin Infect Dis 2012;doi:10.1093/cid/cis933.
Updated HIV Incidence Estimates
A comparison of updated HIV incidence estimates for 2008–2010 revealed two key trends during the 4-year period 2007–2010 among heavily infected populations: a decrease (by 21%) in new HIV infections among black women, and a continuing increase (22%) in new infections among homosexual and bisexual men. Overall, comparing 2008 and 2010, the estimated number of new HIV infections among adults and adolescents in the U.S. remained stable. The rate of new infections in 2010 was 18.8/100,000 population; the most new infections occurred in the 25- to 34-year age group. In 2010, blacks/African Americans continued to be disproportionately affected by HIV infection, accounting for 44% of new infections. The estimated number of new HIV infections among women was 21% lower in 2010 than it was in 2008. During this same period, the estimated number of new HIV infections among men who have sex with men (MSM) increased 12%, and this group continued to be at greatest risk for HIV transmission.
Source: Centers for Disease Control and Prevention. HIV Surveillance Report: Supplemental Report. 2012;17(4). Available at
Atherosclerosis Risk in Children
The risk of atherosclerosis is 2.5-fold higher in HIV-infected children than in youngsters without HIV, emphasizing the importance of preventive strategies and lipid-lowering therapies in this population in addition to antiviral treatment to minimize the potential health risks of cardiovascular disease. In a presentation at the annual EUROECHO and Other Imaging Modalities meeting, held December 5–8, 2012, in Athens, Greece, researchers attributed the increased risk of atherosclerosis in HIV-infected children to a combination of inflammation associated with chronic immune system activation related to the HIV infection, and the effect of many antiretroviral drugs on cholesterol levels—causing elevations in LDL and reductions in HDL levels. With good HIV management, children may live a long time with the infection, and therefore are at greater risk of accumulating substantial atherosclerotic damage from the treatments and the secondary effects of the infection. The researchers also reported the results of imaging studies and the finding that the arteries of the HIV-infected children and adolescents were more rigid and less elastic than those of subjects not HIV-infected.
Source: Press Release. Atherosclerosis found in HIV children. December 5, 2012. Available at:
Economics of ART Versus Circumcision
A study designed to evaluate the economic benefits of two HIV prevention strategies—scaling up treatment as prevention (TasP) versus increasing coverage of medical male circumcision and antiretroviral treatment (ART) at CD4 levels <350/μL—compared the two strategies using a mathematical model applied to South Africa. The results indicated that increased ART and circumcision coverage would provide about the same reduction in HIV incidence as would TasP over the period 2009–2020; however, expanded circumcision and ART would cost a total of about $5 billion less. In terms of the cost per HIV infection avoided, circumcision is much more cost effective than ART or TasP ($1,096 versus $6,790 or $8,375, respectively), but circumcision and ART are comparable in cost per death averted ($5,198 versus $5,604) and $7,739 for TasP. The study authors concluded that in South Africa the most cost-effective HIV prevention strategy would be to expand circumcision coverage and then increase ART coverage. For HIV mortality reduction, the most cost-effective approach would be to scale up circumcision and ART together. While TasP would be both effective and cost-effective, it is not the optimal strategy from an economic perspective.
Source: Bärnighausen T, Bloom DE, Humair S. Economics of antiretroviral treatment versus circumcision for HIV prevention. PNAS 2012;doi:10.1073/pnas.1209017110.
HIV Rates High, Testing Low Among U.S. Youths
The U.S. Center for Disease Control and Prevention (CDC) combined data collected in 2009–2011 from multiple national surveillance systems and surveys to estimate the prevalence rate of diagnosed HIV infections, the number of new infections, the prevalence of risk factors and high risk behaviors, and HIV testing rates among youths—defined as persons aged 13–24 years. In 2009, this population accounted for 6.7% of the estimated 1.1 million people living with HIV infection in the U.S. More than half (59.5%) of these young people did not know they were infected. The prevalence of diagnosed HIV was 69.5/100,000 youths in 2009. In 2010, youths accounted for 25.7% of new HIV infections. Of these new infections, 57.4% were among African Americans, 19.6% were among Hispanics/Latinos, and 19.5% were among whites; 72.1% were attributed to male-to-male sexual contact.
Testing rates ranged from 12.9% among high school students to 34.5% among young adults 18–24 years of age. Overall, more girls were tested than boys, and testing rates were higher for African Americans than among whites or Hispanics/Latinos.
Source: Centers for Disease Control and Prevention. Vital signs: HIV infection, testing, and risk behaviors among youths—United States. MMWR 2012;61:971–976.
Greater Cognitive Impairment with HIV/HCV-Coinfection
To compare neuropsychological performance among four groups of men—hepatitis C virus (HCV) monoinfected, HIV/HCV coinfected, HIV monoinfected with a controlled viral load, and a control group—a team of researchers defined a global deficit score (GDS) that was calculated based on tests for depression, attention, executive function, information processing, fine motor speed, verbal and visual learning, and memory. Overall, HIV/HCV subjects had significantly higher depression and GDS scores than controls, and a higher GDS score than HCV- and HIV-mono-infected subjects and controls. Within the HCV-infected group, higher viral load correlated with lower attention, executive function, and information processing speed, and with a worse GDS.
Source: Sun B, Abadjian L, Rempel H, et al. Differential cognitive impairment in HCV coinfected men with controlled HIV compared to HCV monoinfection. J Acq Imm Def Synd 2012;doi:10.1097/QA1.0b013e31827b61f1.
ART and Malaria Prevention
Based on in vitro evidence showing that protease inhibitors used for ART therapy to treat HIV infection are active against Plasmodium falciparum in vitro at lopinavir levels achievable in humans, a team of researchers designed a study to test the hypothesis that HIV-infected children in Uganda receiving lopinvir-ritonavir-based ART would have a lower incidence of malaria than those receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART. Children ranging in age from 2 months to 5 years were randomly assigned to one of the two treatment groups and followed for 6 months to 2 years. A significantly lower (41%) incidence of malaria was reported in the lopinavir-ritonavir group than among those receiving the NNRTI-based regimen (1.32 versus 2.24 episodes per person-year). The risk of malaria recurrence after treatment with artemether-lumefantrine was also significantly lower in the lopinavir-ritonavir group (28.1% versus 54.2%). The researchers proposed three possible mechanisms for the protective effects of the lopinavir-ritonavir regimen: direct antimalarial activity; inhibition of lumefantrine metabolism, prolonging posttreatment prophylaxis; or antimalarial synergy between lumefantrine and lopinavir. Direct antimalarial effects of protease inhibitors could result from inhibition of plasmodial aspartic proteases that share biochemical properties with HIV protease, but as the study results showed greater protection against recurrent malaria than against a first episode, the principal effect of lopinavir-retonavir was more likely on lumefantrine exposure. The authors concluded that, “a strategy of pharmacologic enhancement of exposure to antimalarial agents may be useful in reducing the burden of malaria, particularly in areas where the transmission intensity is high and recurrent malaria after treatment is commonplace.”
Source: Achan J, Kakuru A, Ikilezi G, et al. Antiretroviral agents and prevention of malaria in HIV-infected Ugandan children. N Engl J Med 2012;367:2110–2118.
Anti-HIV Antibody Therapy Deserves Another Look
New, more potent human antibodies to human HIV-1 that have been improved using techniques such as structure-based design have the potential to provide effective control of HIV-1 infection and to suppress viral loads to below detectable levels, if administered in combinations, to prevent against the phenomenon of viral escape that can occur with antibody monotherapy. Combinations of broadly neutralizing antibodies can control a range of viral isolates and, compared to antiretroviral therapy, provide viremic control of longer duration after cessation of therapy—on average, 60 days—due to their longer half-life. Thus, combination monoclonal antibody therapy should be re-evaluated for its potential as a viable therapeutic strategy in HIV-1 infected individuals.
Source: Klein F, Halper-Stromberg A, Horwitz JA, et al. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature (Letter) 2012;492:118.
Hepatitis B and C
Liver Meeting Highlights
Key developments reported at the Liver Meeting, organized by the American Association for the Study of Liver Disease (AASLD) and held November 9–13 in Boston, MA, were highlighted in a blog by Corinna Dan, RN, MPH, Viral Hepatitis Policy Advisor, Office of HIV/AIDS and Infectious Disease Policy, U.S. Department of Health and Human Services. The new standard-of-care for chronic hepatitis C virus (HCV) infection—triple therapy that includes one of two recently approved oral agents (telaprevir or boceprevir) combined with pegylated interferon and ribavirin—yields improved outcomes and cure in up to 80% of people who complete treatment, and within as short a treatment period of 6–12 months; however, this regimen is not without side effects. Ms. Dan reported that there are more than 30 new drugs to treat HCV infection in development, and there is hope that some may achieve 100% cure rates. New second-generation oral drugs are expected to be available within the next 2 years.
Regarding hepatitis B virus (HBV) infection, presenters spoke of a growing understanding of how the virus harms the liver; how to treat patients with chronic HV infection, including what combination of drugs are most effective; how to reduce the risk of liver cancer; and how to prevent transmission of the virus from mother to infant.
Ms. Dan summarized a series of presentations by representatives of federal groups involved in implementing the Viral Hepatitis Action Plan, intended to improve testing, care, and treatment for the prevention of liver disease and liver cancer. She encourages members of AASLD and health care professionals in general not only to provide direct care for patients with chronic HBV and HCV infection, but also to help expand access to specialty care for these patients.
Source: Dan C. (blog). Highlights from the Liver Meeting. Available at:
Triple Therapy Okay in Setting of HCV & Cirrhosis
As part of a French early access program called CUPIC, patients with hepatitis C virus and cirrhosis who did not respond to standard therapy received triple therapy with telaprevir or boceprevir in combination with peg-interferon and ribavirin. Results at week 16 show that triple therapy correlates with higher sustained virologic response (SVR) rates but also a higher rate of serious adverse events (greater with telaprevir), mainly anemia. At 16 weeks of treatment, HCV-RNA was undetectable in 86% of the telaprevir-treated group and 71% of the boceprevir-treated cohort. The presenters of these results—in Abstract 51 at the AASLD's recent Liver Meeting in Boston, MA—concluded: “Cirrhotic experienced patients should be clearly treated but cautiously and carefully monitored.”
Source: Hezode C, Dorival C, Zoulim F, et al. Safety and efficacy of telaprevir or boceprevir in combination with peginterferon alfa/ribavirin in 497 cirrhotic non responders. Week 16 analysis of the French early access program (ANRS CO20-CUPIC) in real-life setting. Presented at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2012), November 9–13.
Human Papillomavirus Infection
Reactivation of latent human papillomavirus (HPV) has been proposed as one explanation for the bimodal prevalence of HPV seen in some populations of women, with a second peak in HPV detection occurring around the time of menopause. A 2-year study of women aged 35–60 years and followed semiannually led to the following results: the age-specific prevalence of high-risk HPV genotypes decreased with increasing age among women who had less than 5 lifetime sex partners; it did not decline with age among women with 5 or more lifetime sex partners, and the difference in HPV prevalence between these two groups was statistically significant. The estimated population-attributable risk (PAR) for high-risk HPV associated with ≥5 lifetime sex partners was higher among older women (87.2%) compared to younger women (28.0%), but the reverse was true for the risk associated with a new sex partner—7.7% for older women and 28% for younger women. At about age 50, HPV reactivation may have a greater effect on overall HPV prevalence than new acquisition, but the study authors conclude that older women, “with a sexual debut before the sexual revolution” have a lower cumulative probability of HPV infection that “may be masking an age-related increase in HPV reactivation in the United States.”
Source: Gravitt PE, Rositch AF, Silver MI, et al. A cohort effect of the sexual revolution may be masking an increase in human papillomavirus detection at menopause in the United States. J Infect Dis 2013;207:272–280.