in september 2007 that the trial for v520 would be stopped after it determined that vaccination with v520 appeared associated with an increased risk of hiv infection in some recipients. the foremost issue facing the recombinant adenovirus that was used is the high prevalence of the adenovirus-specific antibodies as a result of prior exposure to adenovirus. adenovirus vectors and many other viral vectors currently used in hiv vaccines will induce a rapid memory immune response against the vector. this results in an impediment to the development of a t cell response against the inserted antigen (hiv antigens) the results of the trial prompted the reexamination of vaccine development strategies. hvtn 505, a phase iib study, was launched in 2009 but halted in 2013 due to meeting requirements of futility. potential broadly neutralizing antibodies have been cloned in the laboratory (monoclonal antibodies) and are being tested in passive vaccination clinical trials. in may 2016, there was the launch of the antibody mediated prevention (amp) trials (hvtn 703 and hvtn 704), the first phase iib trials of a monoclonal antibody for hiv prevention. hvtn 703 and hvtn 704 found that the vrc01 monoclonal antibody, which targets the cd4 binding site, was not able to prevent hiv acquisition. in 2017, janssen and the hvtn launched the phase iib trial called hvtn 705/imbokodo, testing the mosaic vector vaccine ad26.mos4.hiv and the aluminum phosphate-adjuvanted clade c gp140 vaccines which are designed to prevent infection of all hiv subtypes around the world. in 2021 the nih announced that the imbokodo phase 2b study did not provide statistically significant reduction in hiv infection. in 2019, terevac-vih, a vaccine from cuba, was determined to have passed the first stage of clinical trials after two years and move to the second stage of development. therapeutic hiv vaccines biosantech developed a therapeutic vaccine called tat oyi, which targets the tat protein of hiv. it was tested in france in a double-blind phase i/ii trial with 48 hiv-positive patients who had reached viral suppression on highly active antiretroviral therapy and then stopped antiretrovirals after getting the intradermal tat oyi vaccine. phase iii preventive hiv vaccines there have been no passive preventive hiv vaccines to reach phase iii yet, but some active preventive hiv vaccine candidates have entered phase iii. in february 2003, vaxgen announced that their aidsvax b/e vaccine was a failure in north america as there was not a statistically significant reduction of hiv infection within the study population. aidsvax b/e was a component, along with alvac, of the rv 144 vaccine trial in thailand that showed partial efficacy in preventing hiv. the aidsvax b/e and alvac vaccines targeted the gp120 part of the hiv envelope. the study involved 16,395 participants who did not have hiv infection, 8197 of whom were given treatment consisting of two experimental vaccines targeting hiv types b and e that are prevalent in thailand, while 8198 were given a placebo. the participants were tested for hiv every six months for three years. after three years, the vaccine group had hiv infection rates reduced by about 30% compared with those in the placebo group. however, after taking into account the seven people who already had hiv before getting vaccinated (two in the placebo group, five in the vaccine group) the difference was 26%. it was discovered that participants receiving vaccines in the rv 144 trial who produced igg antibodies against the v2 loop of the hiv outer envelope were 43% less likely to become infected than those who did not, while iga production was associated with a 54% greater risk of infection than those who did not produce the antibodies (but not worse than placebo). viruses collected from vaccinated participants had mutations in the v2 region. tests of a vaccine for siv in monkeys found greater resistance to siv in animals producing antibodies against this region. therefore, further research is expected to focus on creating vaccines designed to provoke an igg reaction against the v2 loop. in 2020, the phase iib-iii trial hvtn 702/"uhambo" found that alvac/gp120/mf59 vaccinations were safe, and caused no harm, but had no efficacy in hiv prevention in south africa. vaccinations with the uhambo vaccine regimen began late 2016 and stopped early 2020. in 2020, the ad26.mos4.hiv plus adjuvanted clade c gp140 vaccine regimen entered a phase iii trial called hvtn 706/"mosaico". the regimen is a combination of an adenovirus vector vaccine engineered against multiple global strains of hiv, and a protein vaccine. the trial was ended in january 2023 due to ineffectiveness. therapeutic hiv vaccines no therapeutic hiv vaccine candidates have reached phase 3 testing yet. economics a july 2012 report of the hiv vaccines & microbicides resource tracking working group estimates that $845 million was invested in hiv vaccine research in 2011. economic issues with developing an hiv vaccine include the need for advance purchase commitment (or advance market commitments) because after an aids vaccine has been developed, governments and ngos may be able to bid the price down to marginal cost. classification of possible vaccines theoretically, any possible hiv vaccine must inhibit or stop the hiv virion replication cycle. the targets of a vaccine could be the following stages of the hiv virion cycle: stage i. free state stage ii. attachment stage iii. penetration stage iv. uncoating stage v. replication stage vi. assembling stage vii. releasing therefore, the following list comprises the current possible approaches for an hiv vaccine: filtering virions from blood (stage i) biological, chemical and/or physical approaches for removing the hiv virions from the blood. approaches to catching the virion (stage i-iii, vi, vii) phagocytosis of the hiv virions. chemical or organically based capture (creation of any skin or additional membrane around the virion) of hiv virions chemical or organic attachments to the virion approaches to destroying or damaging the virion or its parts (stage i-vii) here, "damage" means inhibiting or stopping the ability of virion to process any of the phase ii-vii. here are the different classification of methods: by nature of method: physical methods (stage i-vii) chemical and biological methods (stage i-vii) by damaging target of the hiv virion structure: damaging the docking glycoprotein gp120 (stage i-iii, vi, vii) damaging the transmembrane glycoprotein gp41 (stage i-iii, vi, vii) damaging the virion matrix (stage i-iii, vi, vii) damaging the virion capsid (stage i-iii, vi, vii) damaging the reverse transcriptase (stage i-vii) damaging the rna (stage i-vii) blocking replication (stage v) insertion into blood chemical or organic compounds which binds to the gp120. hypothetically, it can be pieces of the cd4 cell membranes with receptors. any chemical and organic alternative (with the ability to bind the gp120) of these receptors also can be used. insertion into blood chemical or organic compounds which binds to the receptors of the cd4 cells. biological, chemical or physical approaches to inhibit the process of phases biological, chemical or physical approach to inhibit the attachment, penetration, uncoating, integration, replication, assembling and/or releasing. inhibiting the functionality of infected cells (stage vi-vii) inhibiting the life functions of infected cells: inhibiting the metabolism of infected cells inhibiting the energy exchange of infected cells future work there have been reports that hiv patients coinfected with gb virus c (gbv-c), also called hepatitis g virus, can survive longer than those without gbv-c, but the patients may be different in other ways. gbv-c is potentially useful in the future development of an hiv vaccine. live attenuated vaccines are highly successful against polio, rotavirus and measles, but have not been tested against hiv in humans. reversion to live virus has been a theoretical safety concern that has to date prevented clinical development of a live attenuated hiv-1 vaccine. scientists are researching novel strategies to develop a non-virulent live attenuated hiv-1 vaccine. for example, a genetically modified form of hiv has been created in which the virus's codons (a sequence of three nucleotides that form genetic code) are manipulated to rely on an unnatural amino acid for proper protein translation, which allows it to replicate. because this amino acid is foreign to the human body, the virus cannot reproduce.