Abstract
HIV Infection
cART Protests Against Non–AIDS-Defining Cancers
HIV-infected individuals have an increased risk of AIDS-defining or virus-related cancers, but the same is not necessarily true of non–AIDS-defining cancers. In a retrospective study of more than 5,000 HIV-infected patients registered with a local HIV clinic in Italy, researchers linked individual patient records from the HIV clinic with those in the general local health authority database and the local cancer registry across a 10-year period. They determined cancer rates and evaluated factors associated with the development of non–virus-related, non–AIDS-defining cancers. This risk was only increased—by twofold—in HIV-infected males, and was greatest for lung and testicular cancer. Two of the factors studied were predictive of increased risk for non-viral/non–AIDS-related cancers: older age and shorter or no exposure to combined antiretroviral therapy (incidence rate ratios of 1.10 and 2.31, respectively). Use of cART appeared to be protective against the development of these malignancies.
Source: Albini L, Calabresi A, Gotti D, et al. Burden of non-AIDS-defining and non-virus-related cancers among HIV-infected patients in the combined antiretroviral therapy era. 2013;29: doi:10.1089/aid.2012.0321.
HIV Vaccine Failures and the Role of Adenovirus
Recent HIV vaccine trial failures have cast doubt on the underlying methodology and, in particular, the particular vector used to deliver the HIV DNA payload intended to stimulate an immunoprotective response. These disappointing outcomes will likely turn back the clock on hopes for a safe and effective vaccine. The latest example, the U.S. based HVTN 505 study, came to an early end in April. The NIH had invested more than $77 million over 11 years in the study, which evaluated a combination of two vaccines. Preliminary results indicated that 41 individuals who received the HIV DNA-containing vaccine became HIV-infected during the course of the study, compared to 30 participants who were not vaccinated. Suspicions as to why the study may have failed are now being cast on the adenovirus vector (Ad5) used in one of the vaccine constructs in the HVTN 505 study.
Source: Cohen J. More woes for struggling HIV vaccine field. Science 2013;249:667.
Cardiac Effects of Long-Term ART in Children
Heart failure is more common in HIV-infected children, but highly active antiretroviral therapy can be cardioprotective, and prolonged exposure to HAART does not appear to impair heart function in pediatric patients.
A study to assess the effects of long-term HAART in children gathered echochardiographic measures of left ventricular function and structure in three pediatric populations: perinatally HIV-infected children receiving HAART; HIV-exposed but uninfected children; and HIV-infected and mostly HAART-unexposed children. Measures of cardiac function (including LV contractility and fractional shortening) were significantly lower for the HIV-infected children not receiving HAART. Among the HIV-infected children overall, measures of cardiac function were lower in association with lower nadir CD4 percentage and a higher current viral load.
Source: Lipshultz SE, Williams PL, Wilkinson JD. Cardiac status of children infected with human immunodeficiency virus who are receiving long-term combination antiretroviral therapy results from the adolescent master protocol of the multicenter pediatric HIV/AIDS cohort study. JAMA Pediatr 2013:1–8.
Progress in African AIDS Response
Coinciding with the 21st summit of the African Union, the Joint United Nations Programme on HIV/AIDS (UNAIDS) released its new Update report highlighting the progress made in response to the spread of AIDS across Africa. Bearing a disproportionate burden of the AIDS epidemic, Africa is home to 69% of the people living with HIV globally. The newly reported numbers and trends were encouraging. For example, 7.1 million people in Africa were receiving antiretroviral treatment in 2012, a substantial increase from less than 1 million reported in 2005. The figure rose by nearly 1 million in 2012 alone. In addition, the trend in declining AIDS-related deaths and numbers of new HIV infections continued, dropping by 32% from 2005 to 2011 and by 33% from 2001 to 2011, respectively. The report attributes these positive trends to strong leadership and shared responsibility both within Africa and across the global community. Despite the encouraging trends, 1.8 million new cases of HIV infection were reported across Africa in 2011 and 1.2 million people there died of AIDS-related illnesses that year. The UNAIDS Update report highlighted specific examples of leadership and a strong AIDS response effort. These included the scale-up of access to HIV treatment in South Africa, with a 20% increase in the number of HIV-infected individuals receiving therapy in the period 2011–2012. In 16 countries, more than 75% of HIV-infected pregnant women receive antiretroviral drugs to prevent mother-to-child transmission.
In the Update report, Michel Sidibé, Executive Director of UNAIDS, commented on the post-2015 agenda, emphasizing that a continued focus on and attention to the AIDS response post-2015 would also contribute to progress on other global health priorities by helping to leverage the power of culture and communities, build strong and accountable global health institutions, mobilize the needed financial commitments from both domestic and international sources, and elevate health as a force for social transformation.
Source: Press release: UNAIDS reports more than 7 million people now on HIV treatment across Africa—with nearly 1 million added in the last year—while new HIV infections and deaths from AIDS continue to fall. UNAIDS. May 21, 2013. Available at
Early Trial Data Indicate Viral Reservoir Depletion
Sangamo Biosciences (Richmond, CA) reported preliminary data from an open-label Phase 1 clinical trial designed to assess the safety and tolerability of single infusions of an escalating dose of autologous CD4+ T cells that have been genetically modified at the CCR5 gene locus using CR5-specific zinc finger nucleases (ZFNs)—a treatment called SB-728-T. The nine trial participants were HIV-positive, had sub-optimal T-cell levels, and had no detectable viral load on long-term ART. They continued their existing antiviral therapy while adding SB-728-T to their treatment regimen. The early results indicate that following a single infusion of the patient's own modified T-cells there was a durable increase in the total CD4 T-cell count. Furthermore, the extent of exposure to circulating ZFN-CCR5 protected CD4 cells correlated with a long-term decrease in the peripheral blood mononuclear cell (PBMC) HIV reservoir, based on proviral DNA measurements. The company also reported that two of the subjects showed a decrease of greater than one log in their viral load during a 16-week treatment interruption, and one of the subjects achieved a transiently undetectable viral load during this period.
Source: Press release: Sangamo BioSciences presents clinical data demonstrating HIV reservoir reduction in HIV-infected subjects treated with ZFP Therapeutic®, SB-728-T. May 15, 2013. Available at
Marriage a Risk Factor for HIV Infection in Malawi
Malawi has one of the highest HIV prevalence rates in the world. A recent study found that as many as two-thirds of new HIV cases in Malawi involve one partner in an ongoing heterosexual relationship in which neither partner is a client of sex workers. The risk of infection for women is affected by the gender inequalities that characterize marital relationships, making marriage a risk factor for HIV infection. Based on focus group discussions with women attending HIV clinics, a team of researchers explored how and why the women were involved in marital relationships, and the effects of marriage on their lives and their HIV risks. The study describes women's lives during one or more marriages, and after separation, abandonment, or widowhood, and presents recommendations for minimizing the HIV risks related to marriage. Factors related to HIV risk include gender inequality and poverty.
Source: Mkandawire-Valhmu L, Wendland C, Stevens PE, et al. Marriage as a risk factor for HIV: learning from the experiences of HIV-infected women in Malawi. Global Public Health 2013;doi: 10.1080/17441692.2012.761261.
Patient-Provider Relationship is Important to Follow-Up
To determine whether better communication and improved relationships between patients and providers can enhance patient retention in HIV care, a group of researchers from Johns Hopkins University (Baltimore, MD) conducted a survey of more than 1,300 participants who attended an urban, academic HIV clinic. The patients rated the quality of their interactions with providers in five main areas: whether they were being treated with dignity and respect; whether they were being listened to carefully; whether they were having things explained in ways they could understand; whether the provider knows them as a person; and whether they were involved in decision-making. Higher ratings in the first four areas all correlated with patients being more likely to keep their appointments, whereas high ratings on involving patients in decision-making was not associated with improved attendance at appointments.
Source: Flickinger TE, Saha S, Moore RD, Beach MC. Higher quality communication and relationships are associated with improved patient engagement in HIV care. J Acq Immune Def Syn. 2013;doi: 10.1097/QAI.0b013e318295b86a.
HPV Infection
Influence of Threat and Efficacy Messages on HPV Vaccination
A post-test experiment designed to evaluate the influence of a serial mediation model of message framing on intentions to talk to a doctor about the HPV vaccine included college-age women and their parents. Based on the Extended Parallel Process Model (EPPM), the study focused on the role of threat and efficacy as serial mediators. The results indicated that for the young women, when messages related to HPV vaccination were framed in relation to the prevention of genital warts, versus cancer prevention, the women's perceptions of self-efficacy increased significantly, which enhanced response efficacy perceptions and, in turn, increased their intentions to talk to a doctor about the HPV vaccine. In contrast, message framing had no effects among the parents, but response efficacy was a significant mediator of self-efficacy and behavioral intentions in both groups of subjects.
Source: A serial mediation model of message framing on intentions to receive the human papillomavirus (HPV) vaccine: revisting the role of threat and efficacy perceptions. Health Communications 2013;28:5–19.