Fighting HIV with HIV

This article presents a new possibility for therapy and treatment of human immunodeficiency virus infection.     

HIV antibodies for treatment of HIV infection

The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Furthermore, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small-molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure.     

Mechanisms of HIV persistence in HIV reservoirs

The establishment and maintenance of HIV reservoirs that lead to persistent viremia in patients on antiretroviral drugs remains the greatest challenge of the highly active antiretroviral therapy era. Cellular reservoirs include resting memory CD4+ T lymphocytes, implicated as the major HIV reservoir, having a half‐life of approximately 44 months while this is less than 6 hours for HIV in plasma. In some individuals, persistent viremia consists of invariant HIV clones not detected in circulating resting CD4+ T lymphocytes suggesting other possible sources of residual viremia. Some anatomical reservoirs that may harbor such cells include the brain and the central nervous system, the gastrointestinal tract and the gut‐associated lymphoid tissue and other lymphoid organs, and the genital tract. The presence of immune cells and other HIV susceptible cells, occurring in differing compositions in anatomical reservoirs, coupled with variable and poor drug penetration that results in suboptimal drug concentrations in some sites, are all likely factors that fuel the continued low‐level replication and persistent viremia during treatment. Latently, HIV‐infected CD4+ T cells harboring replication‐competent virus, HIV cell‐to‐cell spread, and HIV‐infected T cell homeostatic proliferation due to chronic immune activation represent further drivers of this persistent HIV viremia during highly active antiretroviral therapy.     

Pediatric HIV

The experiences of several HIV-infected children are highlighted to illustrate the importance of parents' and guardians' understanding the need for treating their HIV-infected children. Children face the same treatment issues as adults, but sometimes react differently to medications, and may require treatment changes if problems occur. Healthcare providers agree that HIV-infected children live longer and avoid illness when treated with HIV drugs. Those on no therapy become more withdrawn, miss school more often, and become increasingly dependent on their guardians. Theoretically, children may be able to achieve more immune cell restoration than do adults whose nervous and immune systems are mature. Children who are HIV-treated have shown considerable growth and development compared to untreated children who may develop complications such as cancer. Early HIV treatment before age one may lessen disease severity. A list of resources for parents and guardians is provided.     

HIV fusion inhibitors

Drugs based on amino acid sequence of Heptad Repeats of gp41 of HIV have been explored in search of anti‐HIV drugs acting by inhibition of the gp41 6‐helix formation and subsequent cellular infection. These are classified under a distinct discipline called HIV fusion inhibitors. Resistance to HIV fusion inhibitors and their solutions have also been discussed in this review. Copyright © 2009 John Wiley & Sons, Ltd.