Abstract
HIV Infection
Understanding How HLA-B57 Variants Delay Disease Progression
Using the Multicenter AIDS Cohort Study to identify HIV-1–infected individuals who carry the HLA-B57 allele and whose time to development of disease ranged from 3.5 years to longer than 25 years after infection, a group of researchers examined early HIV-1–specific cytotoxic T lymphocyte responses in these patients. Overall, the researchers reported that targeting of a broader range of epitopes from structural proteins, and especially Gag, and of highly conserved epitopes from any HIV-1 protein, was associated with longer disease-free intervals post-infection. Specifically, early HLA-B57–restricted CD8+ T lymphocyte responses to the IW9 epitope of Gag correlated with delayed progression to disease.
Source: Brennan CA, Ibarrondo FJ, Sugar CA, et al. Early HLA-B*57-restricted CD8+ T lymphocyte responses predict HIV-1 disease progression. J Virol 2012;86:10505–10516.
HIV Exposure Laws Do Not Reduce Sexual Risk Behavior
The results of an anonymous survey of HIV-infected people conducted in New Jersey showed that 51% of participants were aware of the state's HIV exposure law. Awareness of the law did not correlate with an increase in sexual abstinence, condom use with their most recent sexual partner, or disclosure of their seropositive status. While it has been hypothesized that people who are unaware of the disclosure law would experience greater stigma and would be less comfortable disclosing their HIV-positive status, the results of the survey did not support these hypotheses. The authors of the study concluded that criminalization of HIV nondisclosure is not an effective strategy for deterring sexual risk behavior and that the HIV exposure laws are not likely to reduce HIV transmission.
Source: Galletly CL, Glasman LR, Pinkerton SD, and DiFranceisco W. New Jersey's HIV exposure law and the HIV-related attitudes, beliefs, and sexual and seropositive status disclosure behaviors of persons living with HIV. Am J Public Health. 2012;102:2135–2140.
False-Negative Confirmatory HIV Test Results Are Common in Children
According to World Health Organization (WHO) guidelines, children diagnosed with HIV based on a clinical diagnosis or single virologic test before the age of 18 months should undergo confirmatory HIV antibody testing after 18 months of age. A study of 109 children who met the above criteria and had a positive HIV DNA PCR test to make the initial diagnosis, underwent confirmatory HIV rapid testing. The results indicate that 22 (20.2%) had a negative rapid test result and 27 (24.8%) had a discordant result on confirmatory testing. Of these 49 children, 46 were receiving antiretroviral therapy. Further testing of these 49 children resulted in 11 of 24 negative HIV DNA PCR test results and 9 of 10 positive HIV ELISAs. Only two of the 49 children were uninfected, 29 were definitely and 17 probably HIV-infected, and one child's HIV status could not be determined. The authors cautioned that false-negative confirmatory rapid HIV tests and HIV DNA PCR results in children on ART are both relatively common and “may lead to inappropriate ART discontinuation and discharge from care of truly HIV-infected children.”
Source: Garcia-Prats AJ, Draper HR, Sanders JE, et al. False-negative post–18-month confirmatory HIV tests in HIV DNA PCR-positive children: A retrospective analysis. AIDS 2012;26:1927–1934.
On-Site Rapid HIV Testing Is Cost-Effective in Substance Abuse Programs
Even though offering HIV screening and prevention services as part of a substance abuse treatment is a component of the President's National HIV/AIDs Strategy, HIV testing on-site or through referral is available at less than half of community-based substance abuse treatment centers in the U.S. A randomized trial that included 12 such programs evaluated the cost-effectiveness of three HIV testing strategies: referral for off-site HIV testing; on-site rapid HIV testing with results reporting only, or on-site rapid testing with risk-reduction counseling. The authors determined that on-site testing with information reporting only was more efficient than referral and was cost-effective based on the ratio of cost to quality-adjusted life years for HIV-infected individuals. The addition of on-site risk reduction counseling added costs without additional benefit.
Source: Schackman BR, Metsch LR, Colfax GN, et al. Drug Alcohol Depend. September 6, 2012 Epub:
Delivery of Anti-HIV Microbicide in Intravaginal Ring Shows Promise
Previous work showed that an intravaginal ring impregnated with the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 provided partial protection against simian HIV reverse transcriptase (SHIV-RT) infection in macaques. By adding zinc acetate, significant protection could be achieved with the NNRTI gel. A new study evaluated the activity of MIV-150 without the addition of zinc acetate when delivered using two different types of intravaginal rings: comprised of either ethylene vinyl acetate or silicon. Radioimmunoassay detection of MIV-150 in vaginal fluid collected from the macaques indicated that MIV-150 was successfully delivered by both intravaginal rings; the ethylene vinyl acetate rings were associated with significant protection against SHIV-RT infection.
Source: Singer R, Mawson P, Derby N, et al. An intravaginal ring that releases the NNRTI MIV-150 reduces SHIV transmission in macaques. Sci Transl Med 2012;4:150ra123.
TB and HIV Coinfection Rates Have Stayed Low
More than 600 fewer cases of tuberculosis were reported in the U.S. in 2011 compared to 2010, according to the Centers for Disease Control and Prevention (CDC). Despite this encouraging news, TB “still remains a serious threat, especially for people living with HIV, as HIV can make TB worse,” and is a leading cause of death among HIV-infected individuals worldwide, says Kevin Fenton, M.D., Ph.D., FFPH, Director, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the CDC. The reported numbers of patients with both TB and HIV-positive test results dropped dramatically between 1993 and 2008, from 15% to 6%, and has remained at that lower rate since. From 2010 to 2011, the percentage of people with TB who reported being tested for HIV rose from 67% to 82%. “People living with HIV who also have either latent TB infection or TB disease can be effectively treated,” says Dr. Fenton. The first step is to test HIV-infected individuals for TB infection.
Source: Fenton K. Tracking TB-HIV coinfection in the United States. Available at
The Link Between AIDS and Stomach and Esophageal Cancers
Based on data for nearly 600,000 people with AIDS drawn from the HIV/AIDS Cancer Match Study and collected between 1980–2007, individuals with AIDS appear to be at increased risk for esophageal cancers (adenocarcinoma and squamous cell carcinoma) and stomach carcinomas and for non-Hodgkin lymphomas (NHLs). Whereas the incidence of NHL declined in this population during the study period, likely associated with the development and implementation of improved therapies for HIV infection, the incidence of esophageal cancer and of gastric cancer remained fairly constant over the 27 years.
Source: Disparities in HIV Mortality Trends by Socioeconomic StatusSource: Persson EC, Shiels MS, Dawsey SM, et al. Increased risk of stomach and espophageal malignancies in people with AIDS. Gastroenterol 2012;143:943–950.
Home HIV Testing—A Tool for Screening Partners?
The first over-the-counter HIV test is now available (OraQuick, OraSure Technologies), enabling HIV testing in the privacy of one's home with results available in about 20 min. Some are predicting that the test will be well-received not only for self-testing, but also for testing current or potential sexual partners. Although the manufacturer of the test is not promoting the test as a screening tool, a recent article in The New York Times stated that 70% of the 4,000 subjects who participated in OraQuick clinical trials said they would definitely or be very likely to use the test to screen partners. While some would argue that the $40/test cost might limit this use, others do not see the cost as a deterrent. On the one hand there is the argument that the ability to screen partners and encourage them to take an at-home HIV test before having sex might lead to more HIV-positive individuals learning about their serostatus or, if they already know, choosing to be open and honest about it with a potential partner. Another side of the discussion focuses on the risks involved with a negative test result, which could be a false-negative, and even if a true negative result, could encourage partners to forgo condom use and remove protection from other sexually transmitted diseases. The article discusses the interpersonal and psychological factors involved in talking to partners about being HIV-positive, being truthful, and deciding whether to have unprotected sex, and how access to home-testing could affect those dynamics
Source: McNeil DG. Another use for rapid home H.I.V. test: screening sexual partners. The New York Times. October 5, 2012.
Trends in HIV Mortality and Racial and Socioeconomic Factors
A comparison of HIV mortality trends between 1993–1995 and 2005–2007 revealed the greatest absolute declines in mortality for nonwhites (black and Hispanic men and women), due to their higher baseline rates. However, the data indicated that mortality rates remained relatively high for blacks overall, and disparities were especially evident with decreasing levels of education among black men and women.
Source: Simard EP, Fransua M, Naishadham D, and Jemal A. The influence of sex, race/ethnicity, and educational attainment on human immunodeficiency virus death rates among adults, 1993–2007. Arch Intern Med 2012; doi:10.1001/archinternmed.2012.4508.
HCV Infection
Phase II Combination Drug Trial Planned
A phase IIa interferon-free open label study in patients with chronic hepatitis C virus (HCV) genotype-1a or −1b infection will assess the efficacy, safety, and tolerability of a combination of the protease inhibitor simeprevir and a non-nucleoside inhibitor (NNI) of HCV NS5B polymerase. Simeprevir blocks HCV NS3/4A, and is in phase III clinical development jointly by Medivir AB and Janssen Research & Development Ireland. The second drug in the study, TMC647055, is a NNI being developed by Janssen R&D. The two experimental compounds and ritonavir will be coadministered once a day with or without ribavirin for 12 weeks. The primary endpoint of the trial is sustained virologic response 12 weeks after the end of treatment. The first part of the study will include patients chronically infected with HCV who are either treatment-naive or have relapsed after previous treatment with pegylated interferon/ribavirin; the second part will include patients with chronic HCV infection who were previous null responders.
Source: Press release. A phase IIa interferon free combination hepatitis C trial of Simeprevir (TMC435) and TMC647055 will commence shortly. Available at:
Triple Therapy May Be Safe in Some HIV–HCV Coinfected Patients
Due to the risk of drug–drug interactions, triple therapy for chronic hepatitis C virus (HCV) genotype 1 infection, which combines pegylated interferon, ribaviron, and either boceprevir (BOC) or telaprevir (TVR,) may not be advisable in HIV/HCV-coinfected individuals. Despite the demonstrated effectiveness of BOC and TVR in achieving sustained virological response rates, they are HCV protease inhibitors and share common metabolic pathways with HIV protease inhibitors. However, while there is certainly a risk for drug–drug interactions, and these have been documented in clinical studies, there is not enough evidence whether all coinfected patients share the same risk and whether that is affected by their stage of liver disease. A recent correspondence reports two cases in which HCV triple therapy, including BOC, was administered to coinfected patients receiving an anti-HIV regimen that included an HIV protease. Both patients had liver cirrhosis when HCV triple therapy was initiated. The results indicated that, in these two patients with advanced liver disease, the drug levels of the HIV protease inhibitors remained within the normal range on coadministration of BOC.
Source: Schwarze-Zancer C and Rockstroh JK. HIV protease inhibitors in combination with boceprevir: are drug-drug interactions the same for all patients? [Letter] AIDS 2012;26:1845–1850.