ABSTRACT
In 1981, the emergence of AIDS was first reported, followed by the identification of HIV as the cause of the disease in 1983.1-4 Since then, HIV/AIDS has become a global pandemic, the leading infectious killer, affecting more than 33 million people worldwide.5 HIV infects immune cells, i.e., T-cells, macrophages and dendritic cells6 and spreads by the transfer of body fluids, for example by injections with contaminated needles, sexual contact and from mother to child. In 1987, an early movement was already appealing for a cure for HIV/AIDS that spurred expedited approval by the US Food and Drug Administration (FDA) of the first antiretroviral drug-Zidovudine (AZT)—and made new investigational drugs available for desperately ill patients early in the drug development process.7,8 To date, HIV/ AIDS is treated with the combination of 25 antiretroviral drugs (ARV) that are divided into six classes according to their interference
with the HIV life-cycle: fusion/entry inhibitors, integrase inhibitors, protease inhibitors, non-nucleoside reverse trancriptase inhibitors, nucleoside analog reverse transcriptase inhibitors and multidrug combination products. HIV/AIDS treatment using any single class of ARV has not been efficient in controlling infection due to the development of resistant strains of the virus. Hence, three or more ARVs are used in combination (combination antiretroviral therapy, cART) to treat the disease. cART has been effective in decreasing morbidity and mortality associated with HIV infection.9 Currently available cART are efficacious in providing protection against AIDS with only minimum side effects. Key products used for the treatment of the majority of patients such as Atripla (efavirenz/tenofovir/emtricitabine), Truvada (tenofovir/emtricitabine), Sustiva (efavirenz), Kaletra (lopinavir/ ritonavir), Reyataz (atazanavir) and Isentress (raltegravir) satisfy the ARV drug demand in the market. Successful management of HIV-infected patients is challenging, requiring highly experienced physicians due to resistance and overlapping toxicities of the complex daily ARV regimen that needs to be taken life-long. However, even optimal cART, characterised by suppression of viral load to undetectable levels for years, has not provided a cure to the disease. Patients on optimal cART have 12 years shorter life expectancy than HIV negative people.10,11 In addition, increased AIDS-related and non-AIDS-related morbidity and mortality has been described in a significant proportion of individuals on optimal cART because the lack of normalisation of their CD4+ T cell counts.12 Optimal cART failed to decrease the viral reservoirs, especially in the gut mucosa, where the residual low-level viral replication may be the cause of persistent immune activation that facilitates the progression to AIDS and death.13 HIV producing cells in the reservoirs that are not eliminated by ARV drugs would be susceptible to immune clearance, but long-term optimal cART diminishes HIV-specific T cell responses.14 Therefore, the immune system of successfully treated HIV-infected people is not prepared to decrease viral reservoirs and control the virus replication, if ARVs are irregularly taken. Presently, there are two major unmet needs in HIV treatment: (i) The development of single-tablet regimens that are effective, safe and well tolerated, but do not aim to cure the disease. This approach, pursued by large pharmaceutical companies, utilises
conventional drug formulation; (ii) Nanomaterials are exploited in the development of highly innovative immunotherapies aiming to stop disease progression and cure HIV/AIDS. Nanomedicine stands for the application of nanomaterials in medical technology. The European Commission has adopted cross-cutting definition of nanomaterials to be used for regulatory purposes as being 50% or more of the particles with 1-100 nm size in at least one dimension.15 Structures measuring several hundred nanometers or a few micrometers, however, are also considered under nanotechnology applications.16 Here we review novel disease-modifying treatment approaches that exploit nanomedicine for either drug delivery or induction of HIV-specific immunity with therapeutic vaccines.
