Abstract
HIV and AIDS
Towards an AIDS-Free Generation
It will not be easy to achieve, but scientists can envision the first AIDS-free generation since the disease began. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), speaking at the AIDS 2012 international AIDS conference, told the media that the science to make it happen is available and what is needed is "the political and organizational will to implement what science has given us." More than 30 million people worldwide have died from AIDS and 34 million people are currently infected with HIV, which causes about 2.5 million deaths each year. The NIH has spent $50 billion on AIDS research since 1982. The President's Emergency Plan for AIDS Relief (PEPFAR), a $15 billion effort initiated by George W. Bush in 2003 and revitalized with an additional $48 billion in funding in 2008, has made AIDS therapy available to nearly 4 million people globally. The legislation comes up for Congressional reauthorization in 2013.
Source: Szabo L. AIDS-free generation within reach scientifically. USA Today July 23, 2012.
Achieving Viral Suppression on ART
Estimates of the percentage of HIV-infected patients on antiretroviral therapy (ART) that achieve sustained viral suppression (defined as viral load or plasma HIV RNA level <50 copies/mL) are typically about 77%. Findings have ranged from only 45% in the early 2000s to 87% more recently. A large study of more than 30,000 patients spanning longer than 10 years found sustained viral suppression in 72% of ART users, with less well-controlled viral load commonly associated with poor adherence to medical regimens.
Source: Yehia BR, Fleishman JA, Metlay JP, et al. Sustained viral suppression in HIV-infected patients receiving antiretroviral therapy. JAMA 2012;308:339–342.
Barriers to Controlling HIV Infection Epidemic in MSM
The epidemic of HIV infection among men who have sex with men (MSM) continues to expand globally despite treatment and transmission prevention efforts. A review of data on HIV prevalence, incidence, and risk factors, and of the molecular epidemiology of HIV in MSM between 2007–2011, combined with modeling of the dynamics of HIV transmission during that time period, led to the conclusion that the greatly increased probability of HIV transmission with receptive anal intercourse is a central factor in the disproportionate disease burden in MSM. The study also showed that within the same population, MSM tend to have higher rates of dual-variant and multiple-variant HIV infection than heterosexuals. An obstacle to preventive strategies that involves using antiretroviral therapy to reduce the risk of HIV transmission is the lower health-seeking behavior of MSM in many areas of the world.
Source: Beyrer C, Baral SD, van Griensven F, et al. Global epidemiology of HIV infection in men who have sex with men. The Lancet 2012;380:367–377.
Can Financial Incentives Improve Medication Adherence?
A meta-analysis of 15 randomized and 6 nonrandomized studies that assessed the effects of financial reinforcement interventions on medication adherence across several chronic diseases including HIV infection found that financial reinforcement significantly improved adherence compared to control conditions, with an overall effect size of 0.77. The average effect size was substantially larger for the nonrandomized studies compared to the randomized studies. Characteristics of the financial incentive that increased the effect size were longer duration interventions, average reinforcements of $50 or more per week, and frequency of reinforcement at least weekly.
Source: Petry NM, Rash CJ, Byrne S, et al. Financial reinforcers for improving medical adherence: Findings from a meta-analysis. Amer J Med DOI: 10.1016/j.amjmed.2012.01.003
AIDS Rates on the Rise Again in Uganda
At one point in time as many as a third of the people in some areas of Uganda were infected with HIV, and throughout the 1990s and early 2000s, with a large influx of dollars spend on AIDS prevention efforts–much of it coming from the U.S.–and an aggressive public awareness campaign, that percentage plummeted. But a recent survey has shown that HIV infection rates are once again on the rise and have increased to 7.3% from 6.4% in 2005. During about that same time the U.S. has spent about $1.7 billion to fight AIDS in Uganda. The survey data indicate that HIV and AIDS rates are climbing in both urban and rural areas of the country and that the disease is being spread primarily among married adults. Furthermore, among both men and women, HIV prevalence increases with rising wealth. Various explanations have been proposed for the changing statistics despite the continued flow of funds and focus on prevention efforts. One is a shift from an earlier grass-roots campaign to change behavior and encourage reduction in the number of sexual partners to a greater emphasis on faith-based messages of abstinence, monogamy, and condom use. Uganda is a socially conservative country where homosexuality is outlawed, but some fear that current strategies are only pushing high-risk behaviors further underground rather than discouraging them. Another concern is that earlier success in HIV prevention and medical treatment efforts led to complacency. Problems with corruption due to the large amounts of foreign aid targeting HIV/AIDS is another issue the Ugandan government needs to tackle.
Source: Kron J. In Uganda, an AIDS Success Story Comes Undone. The New York Times. August 2, 2012. Available at
Gay Couples, Condom Use, and Race
The rate of new HIV cases in the U.S. is relatively high among gay men in relationships and black men, yet a study has shown that black men with black partners tend to practice safe sex. White male couples, the study found, are more likely to talk about condom use and discuss the risks and benefits of unprotected sex, but were less likely to use condoms. In contrast, among black gay couples, condom use was a non-decision; "it was 'just understood' that condom use was non-negotiable." The findings for white and interracial couples suggest that the decision not to use condoms is sometimes a calculated risk based on one or both of the HIV-infected partners having a low viral load as a result of treatment and having a reduced risk of transmitting the virus.
Source: Press release. San Francisco State University. For Gay Couples, Condom Decision-making and Condom Use Varies by Race. July 22, 2012. Available at:
A Factor in Decision-Making to Engage in Unprotected Sex
As evidence accumulates to suggest that lower viral load in HIV-infected individuals on an antiretroviral therapeutic regimen may reduce their risk for transmitting HIV to their sexual partners, viral load is increasingly being viewed as a risk reduction strategy. A study of MSM examined this topic by assessing the frequency of viral load discussions and unprotected anal intercourse among primary and casual sexual partners. The results showed that viral load discussions took place in 93% of primary partnerships in which at least one partner was HIV-positive. In casual sexual episodes, unprotected anal intercourse was more frequent when viral load was not discussed (75%) than when it was discussed (56%).
Source: Horvath KJ, Smolenski D, Iantaffi A, et al. Discussions of viral load in negotiating sexual episodes with primary casual partners among men who have sex with men. AIDS Care 2012;24:1052–1055.
Outpatient HIV/AIDS Care
Periodic outpatient care is important throughout the lives of HIV-infected individuals. A multi-site study that included nearly 23,000 adult patients receiving care at clinics in the HIV Research Network between 2001 and 2009 revealed that 21.7% of patients never established HIV care after their first visit. More than half of the patient did not meet the criteria for optimal retention in outpatient care for all the years included in the study period, and nearly 35% were considered lost to follow-up (no visits for >12 months without returning). The subpopulations most likely to establish and continue outpatient care were women, older patients, Hispanics (vs. whites), and patients with CD4 levels ≤50 cells/mL.
Source: Fleishman JA, Baligh Y, Moore RD, et al. Establishment, retention, and loss to follow-up in outpatient HIV care. JAIDS 2012;60:249–259.
The Search for an HIV Cure
An International Research Agenda
Citing the limitations of current combination antiretroviral therapy, a pair of researchers from the University of California, San Francisco, and the Institut Pasteur, Paris, France, are proposing a new approach to combating HIV–an approach that has as its goal a cure for AIDS and HIV infection. They define seven priorities for HIV cure research:
• “Determine the mechanisms that maintain HIV persistence. This includes defining the role of latency, replication and cell proliferation.
• Determine the tissue and cellular sources of persistent HIV infection in animal models and in people who undergo long-term antiretroviral (ARV) treatment.
• Determine the origins of immune activation and inflammation in the presence of ARVs and their consequences for viral persistence.
• Determine host and immune mechanisms that control infection but allow viral persistence.
• Develop and validate assays to measure persistent HIV infection.
• Develop and test therapeutic strategies to safely eliminate latent infection, including reversal of latency and clearing of latently infected cells.
• Develop and test strategies to enhance the host response's capacity to control active viral replication.”
Source: Deeks SG, Barré-Sinoussi F. Towards a cure for HIV. Nature 2012;487:293–294.
VISCONTI Cohort Shows Benefits of Early Treatment
French researchers presented the results of a prospective study of 12 patients called the VISCONTI (Virological and Immunological Studies in CONtrollers after Treatment Interruption) Cohort at the AIDS 2012 meeting in July. The promising findings demonstrate that HIV-positive patients in whom highly active antiretroviral therapy (HAART) was initiated within 10 weeks post-infection and continued for 3 years could interrupt treatment for 6 years or longer and still be able to control the infection with no resurgence and with only extremely low reservoirs of inducible virus. The durable and inducible HIV reservoir was distributed mainly in short-lived CD4+ T cells, which is similar to the natural distribution found in Elite Controllers–HIV-infected individuals able to control virus replication without antiviral medication.
Source: Bacchus C, Hocqueloux L, Avettand-Fenoël, et al. for the VISCONTI and ALT ANRS Study Groups. Distribution of the HIV reservoir in patients spontaneously controlling HIV infection after treatment interruption. Presentation at the XIX International AIDS Conference, Washington, DC, July 22–27, 2012. Oral Abstract THAA0103.
Targeting Reservoirs of Infection
Stem Cell Transplant+ART=No HIV?
What effect does allogeneic stem cell transplantation (alloSCT) have on peripheral blood HIV reservoirs? Two HIV-infected men with long-term disease, viral suppression on ART, and detectable latent virus in circulating lymphocytes underwent alloSCT for the treatment of lymphoma and, within 8 months, as the donor cells gradually replaced the patients' lymphocytes, HIV DNA became undetectable. Both patients had received a reduced-intensity chemotherapeutic conditioning regimen prior to the transplant that allowed them to continue their ART. A team of researchers from Brigham and Women's Hospital, Harvard Medical School, Ragon Institute, and Dana-Farber Cancer Institute, Boston, MA, and Hôpital Saint-Louis, Paris, France, presented the results at the AIDS 2012 conference. However, until a planned interruption of ART and reassessment of the viral load in these patients is undertaken, it will still be speculation as to whether these transplants themselves, without the benefit of using a CCR5 delta32/delta32 donor whose cells would be resistant to HIV, as in the “Berlin patient” cure, can eradicate HIV reservoirs.
Source: Henrich TJ, Sciaranghella G, Li JZ, et al. Long-term reduction in peripheral blood HIV-1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation in two HIV-positive individuals. Presentation at the XIX International AIDS Conference, Washington, DC, July 22–27, 2012. Oral Abstract THAA0101.
Luring HIV Out of Hiding
The ability of the HIV-1 provirus to exist in a latent form in resting CD4+ T cells despite ART stands in the way of curing the infection. A team of researchers led by David Margolis at the University of North Carolina at Chapel Hill performed a translational clinical study to assess the effects of vorinostat, a histone deacetylase inhibitor and FDA-approved anti-cancer drug that can induce the expression of latent HIV in vitro, on circulating resting CD4+ T cells isolated from HIV-infected patients. HIV viremia was fully suppressed by ART in all eight patients participating in the study. In each patient, a single dose of vorinostat led to increased levels of HIV RNA in the resting CD4+ cells, which the researchers described as "proof-of-concept for histone deacetylase inhibitors as a therapeutic class," and which provides new drug targets and strategies for eradicating latent HIV.
Source: Archin NM, Liberty AL, Kashuba AD, et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 2012;487:482–485.
STDs
CDC Changes Gonorrhea Treatment Recommendation
Gonorrhea is the second most common notifiable infection in the U.S., with more than 300,000 cases reported during 2011. Due to reduced susceptibility of urethral Neisseria gonorrhoeae isolates collected in the US during 2006–2011 to the oral antibiotic cefixime, the Centers for Disease Control and Prevention (CDC) has updated its recommendations for treatment of uncomplicated gonorrhea to the following: combination therapy with cefriaxone 250 mg intramuscularly and either axithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days. If cefixime is used, the patient should undergo a test-of-cure at the site of infection 1 week after treatment.
Source: CDC. Update to CDC's Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections. MMWR 2012;61:590–594.