Development of an HIV vaccine attitudes scale to predict HIV vaccine acceptability among vulnerable populations: L.A. VOICES

Background

Decade-long delays in successful implementation of Hepatitis B vaccines and ongoing obstacles in HPV vaccine roll-out suggest the importance of an implementation science approach to prepare for the effective translation of future HIV vaccines from clinical trials into routine practice. The objective of this study was to test HIV vaccine attitude items to develop reliable scales and to examine their association with HIV vaccine acceptability.

Methods

HIV vaccine attitude items were assessed as part of the L.A. VOICES survey, a large-scale study conducted among underserved residents of Los Angeles, to identify factors that may influence HIV vaccine acceptability. Participants (n = 1225) were randomly selected from public STD clinics, needle exchange sites and Latino community clinics using three-stage, venue-based time space sampling.

Results

Exploratory factor analysis across 20 items revealed four distinct factors – mistrust, HIV vaccine social concerns, risk compensation, and altruistic vaccination – with acceptable reliability coefficients for each subscale (Cronbach's α range 0.61–0.84). We found no significant differences in reliability by gender or by vaccine acceptability. Risk compensation (odds ratio (OR) = 1.49; 95% CI = [1.18, 1.89]; p = 0.001) and altruistic vaccination (OR = 1.40; 95% CI = [1.14, 1.71]; p = 0.001) were significantly and positively associated with HIV vaccine acceptability.

Conclusions

We identified four HIV vaccine attitude scales with sound internal reliability parameters. In the aftermath of the first candidate vaccine to demonstrate efficacy against HIV infection, these scales may be helpful in bridging expectable research-to-practice gaps in future HIV vaccine dissemination among populations at risk. As HIV vaccine trials progress in the United States and globally, these measures also may be useful as a tool to assess and facilitate effective responses to community concerns about HIV vaccine trials and to target interventions to support recruitment and mitigate risk compensation.     

A short term projection of HIV infection and AIDS cases in Cameroon.

By September 1991 Cameroon had reported 650 cases of the acquired immune deficiency syndrome (AIDS). The results from the sentinnel surveillance system showed a seroprevalence of human immunodeficiency virus (HIV)1 of 1.3% among pregnant women, 2.5% in people attending sexually transmitted disease clinics and 3.5% in tuberculosis patients in 1990. The estimated number of persons infected with HIV varies between 10,000 and 30,000. The World Health Organization projection model was used to make a short-term projection of HIV infection and AIDS cases; it indicated that the number of persons infected with HIV will double by the year 1995, with an estimated 8500 AIDS cases. Even in a low prevalence country such as Cameroon, the impact of the HIV epidemic is important and will result in a burden for the health care system.     

HIV vaccine strategies

Traditional methods of vaccine development have not produced effective vaccines for several prevalent infectious diseases, including AIDS, malaria and tuberculosis. These difficult diseases call attention to the importance of new approaches that profit from modern technologies. Successful efforts in the past have typically taken advantage of naturally occurring, protective immune responses, but this avenue is not readily available in certain cases, such as in HIV infection, where the immune system rarely confers protective immunity. However, there are alternative strategies and areas of research that may facilitate the development of highly effective vaccines. These include the identification of immunogens that elicit broadly neutralizing antibodies, determination of the molecular and cellular basis for immune responses to the components of the infectious agent, the identification of relevant forms of viral proteins for antigen presentation, stimulation of relevant T-cell types, and enhancement of antigen-presenting, dendritic cell function. Answering these basic research questions will aid in rational vaccine design. It is also extremely important to optimize techniques for the testing and production of new vaccines including the quantitation of immune responses in animals and in humans, identification of surrogate markers of immune protection, streamlined vaccine production, and rapid evaluation of candidate vaccines for testing in clinical trials. We have put these ideas into practice in two recent studies in which we generated enhanced cytotoxic T lymphocyte (CTL) responses, while retaining robust humoral responses, to wild-type viral proteins by immunizing mice with genetically modified forms of HIV-1 Env, Gag and Pol delivered in the form of plasmid DNA expression vectors.     

New FDA drug approval policies and HIV vaccine development.

The need for new drugs to treat AIDS has caused the federal Food and Drug Administration to modify its procedures for reviewing and approving investigational drugs. Even researchers with reservations about the FDA's new policies are receptive to the idea that the drug review process in the United States could be improved, and the same may be true for the procedures by which vaccines are reviewed. Mariner explains why, because of the differences between drugs and vaccines, the FDA's new drug review policies should not be applied to investigational vaccines to prevent HIV infection. Experimental vaccines warrant separate treatment to protect the healthy subjects who receive them. Mariner argues that the FDA should make an explicit decision to continue to review candidate HIV vaccines in its vaccine unit, separately from drugs, with stricter standards of safety and efficacy.     

Measuring HIV vaccine efficacy

Some HIV vaccine candidates have a potential VE I (vaccine efficacy for infectiousness) type effect, which tends to reduce the viral load and may reduce infectiousness of an infected individual. In general, the efficacy of this kind of vaccine is very difficult to assess because it requires information on contacts of vaccinated infected individuals, and current methods to estimate VE I rely on the time elapsed between infections of an individual and his/her sexual partner, thus making infection of the sexual partner necessary to assess the efficacy. To avoid behavioural changes that may affect the estimates, HIV status is kept undisclosed to participants, which raises many ethical questions. Here we present a method that allows immediate notification of HIV status to both members of a couple, reducing the risk of infection when one of them has not been infected and allowing immediate medical treatment. The method allows for estimation of any VE I and VE S (vaccine efficacy for susceptibility) effect, and it is robust to the most common situations found in these type of studies, namely: differential risk of participants, staggered enrollment and small sample sizes.     

A novel non-integrative single-cycle chimeric HIV lentivector DNA vaccine

Novel HIV vaccine vectors and strategies are needed to control HIV/AIDS epidemic in humans and eradicate the infection. DNA vaccines alone failed to induce immune responses robust enough to control HIV-1. Development of lentivirus-based DNA vaccines deficient for integration and with a limited replication capacity is an innovative and promising approach. This type of vaccine mimics the early stages of virus infection/replication like the live-attenuated viruses but lacks the inconvenient integration and persistence associated with disease. We developed a novel lentivector DNA vaccine “CAL-SHIV-IN⁻” that undergoes a single round of replication in the absence of integration resulting in augmented expression of vaccine antigens in vivo. Vaccine gene expression is under control of the LTRs of a naturally attenuated lentivirus, Caprine arthritis encephalitis virus (CAEV) the natural goat lentivirus. The safety of this vaccine prototype was increased by the removal of the integrase coding sequences from the pol gene. We examined the functional properties of this lentivector DNA in cell culture and the immunogenicity in mouse models. Viral proteins were expressed in transfected cells, assembled into viral particles that were able to transduce once target permissive cells. Unlike the parental replication-competent SHIV-KU2 that was detected in DNA samples from any of the serial passage infected cells, CAL-SHIV-IN⁻ DNA was detected only in target cells of the first round of infection, hence demonstrating the single cycle replication of the vaccine. A single dose DNA immunization of humanized NOD/SCID/β2 mice showed a substantial increase of IFN-γ-ELISPOT in splenocytes compared to the former replication and integration defective Δ4SHIV-KU2 DNA vaccine.     

HIV vaccine trial in Kenya

This article presents a trial study of an HIV vaccine in Kenya. A joint Kenyan-Canadian-British HIV vaccine trial was launched in March of 1999. It is supported by the US-based International AIDS Vaccine Initiative (IAVI). STD clinics will be used as the basis of trials, and volunteers will be injected with genetic material developed from local HIV strains (most vaccine research up to this point has involved strains found in Europe or North America). Concerns have been raised that the vaccine could actually cause AIDS. Professor Ndinya Achola of the University of Nairobi denied that there was such a possibility, as the portions used in the vaccine were not infectious and could not revert to a live virus.     

A case for preART-adjusted endpoints in HIV therapeutic vaccine trials

BackgroundIn a randomized, double-blind, placebo-controlled phase 2 clinical trial of Vacc-4x, a peptide-based therapeutic HIV-1 p24^Gag vaccine candidate, 135 HIV-infected participants (vaccine:placebo = 92:43) received a series of six immunizations while on combination antiretroviral therapy (cART). At week 28, all participants underwent an analytical treatment interruption (ATI) for up to 24 weeks. preART VL appeared to be higher among Vacc-4x recipients. Based on a previous analysis, during ATI viral load (VL) appeared to be lower in Vacc-4x recipients, but no difference in CD4 level was observed between Vacc-4x and placebo groups. We propose fold-change-based endpoints and report comparative analyses accounting for imbalanced preART VL and missing data.MethodsAll analyses included per-protocol (PP) participants who received the full immunization and underwent ATI. Linear regression models were used to identify predictors of study endpoints and to estimate the vaccine effect based on fold changes in CD4 counts or VL over preART values at week 40 or at set-point (geometric mean over weeks 48 and 52 values). We adjusted for potential baseline factors and used a multiple imputation approach to account for missing endpoints due to cART resumption or dropout. P-values were adjusted for multiple comparisons using q-values.ResultspreART VL and CD4 count were significant predictors of study endpoints. The vaccine recipients had a higher fold change in week 40 CD4 counts (vaccine vs. placebo mean fold-change difference = 0.08; p = 0.02; q = 0.03), a higher fold change in CD4 count set-point (0.06; p = 0.06; q = 0.07), a lower fold change in week 40 VL (−0.47; p = 0.03; q = 0.05), and a lower fold change in VL set-point (−0.50; p = 0.02; q = 0.03).ConclusionsThese exploratory analyses consistently suggested that Vacc-4x provided positive effects on both CD4 counts and VL. Future HIV therapeutic vaccine studies may adopt similar preART-adjusted endpoints and missing data imputation methods in vaccine effect evaluations.     

Immune response to hepatitis A vaccine in patients with HIV

Objectives

The aim of this study was to evaluate the impact of various factors that may influence the immunologic response to hepatitis A mono-vaccine or hepatitis A/B co-vaccine (Twinrix®) in HIV-infected patients.

Barriers of enrolment in HIV vaccine trials: a review of HIV vaccine preparedness studies

Barriers to participation in an HIV vaccine trial have been examined in many HIV vaccine preparedness studies (VPS). These barriers can be understood in terms of the locus of the barrier (personal vs. social) and the nature of the barrier (risk vs. cost). Another type of barrier is perceived misconceptions. In this systematic review, we categorize barriers, and compare these barriers between the Organization for Economic Co-operation and Development (OECD) countries and the non-OECD countries. In the OECD countries, we retrieved 25 studies reporting personal risks (PR), 9 studies reporting social risks (SR), 10 studies reporting personal costs (PC), and 16 studies reporting misconceptions. In the non-OECD countries, we retrieved 27 studies reporting PR, 19 studies reporting SR, 18 studies reporting PC, 1 study reporting social costs (SC), and 13 studies reporting misconceptions. Important PR were “adverse effects” and “vaccine-induced seropositivity”, “distrust of institutions”, and “temptation to have unsafe sex” in men who have sex with men (MSM). “Discrimination” was a common SR. “Time commitment” was an important PC, and “family commitments” were a SC in one non-OECD country. “HIV infection from the vaccine” was a common misconception. Both the OECD and the non-OECD countries have similar barriers, and people's decisions to participate in a clinical trial involve multiple barriers. However, these barriers apply to hypothetical HIV vaccine trials, and barriers for actual vaccine trials need further assessment.     

First large-scale U.S. trial of HIV vaccine begins soon

VaxGen Inc. has received Food and Drug Administration (FDA) approval to conduct large, full-scale testing on a new version of its HIV vaccine within the United States and Thailand. Thailand's approval is pending. The VaxGen vaccine requires three injections over several months. The U.S. arm of testing seeks gay men and their uninfected partners. The Thai experiment will only involve uninfected injection drug users.     

艾滋病疫苗研究近况

自1981年世界报道首例艾滋病(AIDS)病例以来,艾滋病在全球范围内蔓延扩散,给人类社会造成严重危害。截至2006年底,全球已有6 000多万人感染艾滋病病毒(HIV),并造成200多万人死亡[1]。我国1985年首次报告艾滋病以来,在吸毒人群、有偿供血者、暗娼、性病患者、流动人口中艾滋病病     

Impaired response to hepatitis B vaccine in HIV infected children.

Eighteen human immunodeficiency virus (HIV) vertically infected children (HIV group) and 33 seroreverted children (SR group), who had completed hepatitis B vaccination (Engerix B, 20 micrograms dose) were studied. Four out of 18 (22%) HIV children failed to develop protective antibody levels (anti-HBs titres less than 10 mIU ml-1) compared with 1 out of 33 (3%) SR children (p less than 0.05). Magnitude of response among HIV children was significantly lower than among SR children. In HIV children the probability that anti-HBs titres persist above the protective levels was significantly lower than in the SR group at any time during the 24 month follow-up. These results show that HIV children have a suboptimal response to hepatitis B immunization and the protection is less durable. Further studies are needed to determine the optimal protocol for hepatitis B immunization in HIV children.