A review of vaccines for HIV prevention

HIV/AIDS has become the most devastating pandemic in recorded history. It has killed 40 million people in the last 20 years and the World Health Organisation estimated that at least 14,000 new infections occurred daily in 2001. There will be up to 100 million new infections in the next 10 years (for current updates, visit http://www.unaids.org/epidemic_update/). Most HIV infections occur in the developing world, and the adverse social and economic impact of the HIV/AIDS pandemic, particularly in the developing world, is unprecedented. Highly active antiretroviral therapy (HAART) has had significant effects on HIV/AIDS in the developed world. The drugs have acted to prolong survival, reduce the viral load, and to alleviate suffering. However, the incidence of side effects and resistance is high and the drugs are unaffordable and unavailable in the developing world. HAART regimens are difficult to comply with. Public health efforts to modify the behaviour, attitude and culture that accelerate the spread of HIV/AIDS have had only modest success. There is urgent need for a prophylactic and/or therapeutic HIV vaccine. This is a review of the obstacles and current trends in HIV vaccine development.     

HIV prevention for indigenous people of the Amazon basin.

This study identifies theoretically-based predictors of condom use in a sample of 251 sexually active adults recruited from Sao Gabriel da Cachoeira and six indigneous communities of the Upper Rio Negro region of Amazonas Brazil. The information-motivation-behavioral skills (IMB) model of AIDS-preventive behavior was used to describe the roles of HIV/AIDS knowledge, experiences with and attitudes toward condom use, peer influences, perceived vulnerability, monogamy and behavioral skills. A predictive path analytic model revealed significant predictors of more condom use including male gender, greater sexual HIV knowledge, positive experiences and attitudes about condom use, multiple partners, and greater behavioral skills. Results suggest that attention to behavioral skills for negotiating safer sex and instruction in the correct use of condoms are important elements in reducing high risk behaviors. Increasing the specific knowledge level of indigenous people regarding the complexities of sexual transmission of HIV is crucial and should be addressed. Heightening individuals' understanding of the limited protection of serial monogamy, and the need to conduct gender-specific training for behavior change to reduce transmission of HIV should be an additional goal of Brazilian health professionals. Obstacles to the implementation of the IMB HIV prevention program in Amazonas are noted and an alternative Brazilian HIV/AIDS prevention program is discussed.     

Innate immunity against HIV: a priority target for HIV prevention research

The xenotropic/polytropic subgroup of mouse leukemia viruses (MLVs) all rely on the XPR1 receptor for entry, but these viruses vary in tropism, distribution among wild and laboratory mice, pathogenicity, strategies used for transmission, and sensitivity to host restriction factors. Most, but not all, isolates have typical xenotropic or polytropic host range, and these two MLV tropism types have now been detected in humans as viral sequences or as infectious virus, termed XMRV, or xenotropic murine leukemia virus-related virus. The mouse xenotropic MLVs (X-MLVs) were originally defined by their inability to infect cells of their natural mouse hosts. It is now clear, however, that X-MLVs actually have the broadest host range of the MLVs. Nearly all nonrodent mammals are susceptible to X-MLVs, and all species of wild mice and several common strains of laboratory mice are X-MLV susceptible. The polytropic MLVs, named for their apparent broad host range, show a more limited host range than the X-MLVs in that they fail to infect cells of many mouse species as well as many nonrodent mammals. The co-evolution of these viruses with their receptor and other host factors that affect their replication has produced a heterogeneous group of viruses capable of inducing various diseases, as well as endogenized viral genomes, some of which have been domesticated by their hosts to serve in antiviral defense.     

Passive immunization for the treatment and prevention of HIV infection.

Passive immunization using serum or immunoglobulin preparations has been used in the prophylaxis and treatment of many bacterial and viral diseases. Preliminary attempts to use these methods to prevent HIV infection in chimpanzees have been promising. With the identification of polyclonal and monoclonal antibodies with protective activity against HIV in in vitro systems, the possibility of using these reagents in vivo takes on new relevance. The potential and problems of using passively administered anti-HIV antibodies for HIV prophylaxis and treatment are discussed, as well as the relative merits of polyclonal versus monoclonal reagents.     

Accomplishments in HIV prevention science: implications for stemming the epidemic

The past two decades have witnessed substantial advances in the science of preventing HIV infection. Although important issues remain and there is a need for continuing research, arguably the biggest challenge in preventing HIV transmission is the full implementation of existing preventive interventions worldwide.     

Cellular immunity for prevention and clearance of HIV infection

Despite the major strides that have been made in HIV therapy with the advent of potent anti-retroviral drugs, these medications are quite expensive and are still not readily available for the vast majority of infected individuals worldwide. Even when available, the long-term toxicities associated with anti-retroviral medications and the frequent emergence of drug-resistance mutations can complicate therapy, making the formulation of effective vaccines imperative. This chapter will review the current state of understanding regarding cell-mediated immune responses that are associated with control of HIV replication. This knowledge has generated sound hypotheses regarding the prospects for augmenting cell-mediated immunity through immune-based therapies. With regard to prophylactic vaccines, it is presently unclear which vaccine-induced immune responses will protect against infection. While much progress has been made in formulating vaccine constructs designed to elicit cell-mediated immune responses, sterilizing immunity is unlikely to be achieved with the current vaccines. However, the ability to control viremia and prevent disease progression in animal infection models looks promising. The ability to measure immune responses has also advanced markedly over the past few years and will allow investigators to more accurately measure the immunogenicity of vaccine constructs, and correlate the magnitude and breadth of these responses with protection.     

Occupational HIV infection. Medical workers and HIV prevention

The analysis of the possibility of suffering injuries at a work place, their causes, the knowledge of HIV infection, attitude towards the infected person is presented. The work was carried out, starting from 1990. Every 2 years the anonymous questioning of members of the medical personnel of different specialties at medical institutions of different profile and level was carried out. Five questionings on injuries suffered during work, the knowledge of HIV infection and the attitude of members of the medical profession towards HIV-positive persons. In most cases injuries are inflicted by injection needles (79%), during operations (12%), by splinters of broken medical glassware and appliances (3%) and in other cases (6%). In 91% of cases injuries caused by needles occur in the process of placing caps on the needles. In the course of 9 years changes in the level of knowledge and the attitude towards HIV-infected persons occurred. Changes in the outlook and the knowledge of AIDS were due to the positive influence of intensive education directly at work places.     

Cash transfers for HIV prevention: A systematic review

BackgroundGiven the success of cash programs in improving health outcomes and addressing upstream drivers of HIV risk such as poverty and education, there has been an increasing interest in their potential to improve HIV prevention and care outcomes. Recent reviews have documented the impacts of structural interventions on HIV prevention, but evidence about the effects of cash transfer programs on HIV prevention has not been systematically reviewed for several years.Methods and findingsWe did a systematic review of published and unpublished literature to update and summarize the evidence around cash programs for HIV prevention from January 2000 to December 17, 2020. We included studies with either a cash transfer intervention, savings program, or program to reduce school costs. Included studies measured the program’s impact on HIV infection, other sexually transmitted infections (STIs), or sexual behaviors. We screened 1,565 studies and examined 78 in full-text review to identify a total of 45 peer-reviewed publications and reports from 27 different interventions or populations. We did not do a meta-analysis given the range of outcomes and types of cash transfer interventions assessed. Most studies were conducted in sub-Saharan Africa (N = 23; South Africa, Tanzania, Malawi, Lesotho, Kenya, Uganda, Zimbabwe, Zambia, and eSwatini) followed by Mexico (N = 2), the United States (N = 1), and Mongolia (N = 1)). Of the 27 studies, 20 (72%) were randomized trials, 5 (20%) were observational studies, 1 (4%) was a case–control study, and 1 (4%) was quasi-experimental. Most studies did not identify a strong association between the program and sexual behaviors, except sexual debut (10/18 finding an association; 56%). Eight of the 27 studies included HIV biomarkers, but only 3 found a large reduction in HIV incidence or prevalence, and the rest found no statistically significant association. Of the studies that identified a statistically significant association with other STIs (N = 4/8), 2 involved incentives for staying free of the STI, and the other 2 were cash transfer programs for adolescent girls that had conditionalities related to secondary schooling. Study limitations include the small number of studies in key populations and examining interventions to reduce school costs and matched saving programs.ConclusionsThe evidence base for large-scale impacts of cash transfers reducing HIV risk is limited; however, government social protection cash transfer programs and programs that incentivize school attendance among adolescent girls and young women show the greatest promise for HIV prevention.

Marie Stoner and co-workers assess the evidence on potential benefits of cash transfer interventions for HIV prevention.     

Substance use and HIV disease progression in the HAART era: implications for the primary prevention of HIV

Prior to the era of highly active anti-retroviral therapy (HAART), cohort studies provided equivocal evidence to support the hypothesis that substance use predicts more rapid HIV disease progression. The present review examined the effects of substance use on HIV disease progression in cohort studies with follow-up that continued into the HAART era. Of the 20 studies included in this review, 16 observed that substance use predicted at least one indicator of HIV disease progression. Ten of the 11 studies that followed participants exclusively in the HAART era observed an effect of substance use on HIV disease progression. Findings across studies indicate that stimulant use promotes more rapid HIV disease progression and the effects of substance use on HIV disease progression can persist after controlling for self-reported HAART non-adherence. Future investigations that examine the bio-behavioral pathways whereby substance use promotes HIV disease progression should include: measures of HIV genotypic and phenotypic resistance, multi-method assessment of adherence, and assessment of co-morbid infections that are more prevalent among substance users. Although further mechanistic research is needed, findings from existing cohort studies have clear clinical implications. Implementing screening, brief intervention and referral to substance abuse treatment in HIV medical care could optimize health outcomes and decrease HIV transmission rates by boosting the effectiveness of "Test and Treat" approaches to HIV prevention.     

Optimizing clinical dosing of combination broadly neutralizing antibodies for HIV prevention

Broadly neutralizing antibodies (bNAbs) are promising agents to prevent HIV infection and achieve HIV remission without antiretroviral therapy (ART). As with ART, bNAb combinations are likely needed to cover HIV’s extensive diversity. Not all bNAbs are identical in terms of their breadth, potency, and in vivo longevity (half-life). Given these differences, it is important to optimally select the composition, or dose ratio, of combination bNAb therapies for future clinical studies. We developed a model that synthesizes 1) pharmacokinetics, 2) potency against a wide HIV diversity, 3) interaction models for how drugs work together, and 4) correlates that translate in vitro potency to clinical protection. We found optimization requires drug-specific balances between potency, longevity, and interaction type. As an example, tradeoffs between longevity and potency are shown by comparing a combination therapy to a bi-specific antibody (a single protein merging both bNAbs) that takes the better potency but the worse longevity of the two components. Then, we illustrate a realistic dose ratio optimization of a triple combination of VRC07, 3BNC117, and 10–1074 bNAbs. We apply protection estimates derived from both a non-human primate (NHP) challenge study meta-analysis and the human antibody mediated prevention (AMP) trials. In both cases, we find a 2:1:1 dose emphasizing VRC07 is nearly optimal. Our approach can be immediately applied to optimize the next generation of combination antibody prevention and cure studies.     

Sexual risk behaviors for HIV/AIDS in Chuuk State, Micronesia: the case for HIV prevention in vulnerable remote populations

Background

After the first two cases of locally-acquired HIV infection were recognized in Chuuk State, Federated States of Micronesia (FSM), a public health response was initiated. The purpose of the response was to assess the need for HIV education and prevention services, to develop recommendations for controlling further spread of HIV in Chuuk, and to initiate some of the prevention measures.

Methodology/Principal Findings

A public health team conducted a survey and rapid HIV testing among a sample of residents on the outer islands in Chuuk. Local public health officials conducted contact tracing and testing of sex partners of the two locally-acquired cases of HIV infection. A total of 333 persons completed the survey. The majority knew that HIV is transmitted through unprotected sexual contact (81%), injection drug use (61%), or blood transfusion (64%). Sexual activity in the past 12 months was reported among 159 participants, including 90 females and 69 males. Compared to women, men were more likely to have had multiple sex partners, to have been drunk during sex, but less likely to have used a condom in the past 12 months. The two men with locally acquired HIV infection had unprotected anal sex with a third Chuukese man who likely contracted HIV while outside of Chuuk. All 370 persons who received voluntary, confidential HIV counseling and testing had HIV negative test results.

Conclusions/Significance

Despite the low HIV seroprevalence, risky sexual behaviors in this small isolated population raise concerns about the potential for rapid spread of HIV. The lack of knowledge about risks, along with stigmatizing attitudes towards persons infected with HIV and high risk sexual behaviors indicate the need for resources to be directed toward HIV prevention in Chuuk and on other Pacific Islands.