HIV/AIDS Topic Homepage

 For the first time, the global incidence rate has stabilized. However, within 33 counties globally, 22 within Sub-Saharan Africa alone, the incidence rate has actually been reduced by 25% between 2001 and 2009.

As the therapeutic arsenal is constantly improving, the rate of AIDS-related deaths decreased 19% from 2004 to 2009.⁵ Currently, in low and middle-income countries, about 8 million people receive antiretroviral therapy, this number is 26 times bigger than in 2004.⁶

Retrovirus HIV enters the cells and after its RNA is converted to DNA, it integrates its genetic information in the cell DNA allowing viral reproduction. The cells targeted by HIV are ones that express the CD4 receptor and either coreceptor CCR5 (macrophages) or CXCR4 (T lymphocytes) at their surface.⁷ HIV needs to bind to the CD4 receptor and one of the coreceptors to enter the cell. Finally, the cells infected are destroyed so the HIV infection is characterized by a progressive loss of CD4+ T cells, weakening the immune system.^7,3 Once the immune system is weakened enough, an opportunistic infection may develop and eventually kill the person infected.^7,3  

The diagnosis of HIV infection is performed by a blood test and the diagnosis of AIDS is established when the number of CD4+ T cells (CD4+ T cell count) is equal to or below 200 per microlitre of blood (healthy people have 800-1300 per microlitre).³ The time between HIV infection and AIDS diagnosis is usually about 8-10 years.³

Two elements are measured in a patient with HIV: the CD4+ T cell count and the plasma HIV RNA (viral load).^3,8
The CD4+ T cell count is used to evaluate immune function, to decide when to start an antiretroviral therapy and prophylaxis for opportunistic infections ^3,8 and to monitor therapeutic response.⁸
The viral load assessment determines how contagious the patient is and evaluates the progression of the disease and the efficiency of the treatment. Treatment aims to control the viral load.^3,8

Due to its modes of transmission, HIV infection is almost completely preventable. The different methods of prevention include using condoms, sexual abstinence or use of topical gels containing antiretroviral drugs, use of clean needles and the wearing of protection (e.g. glove, mask) for people in contact with contaminated body fluids. ³ Some studies have shown some efficiency of male circumcision for heterosexuals.⁹

Through HIV testing, along with the implementation of awareness campaigns and education programs, the number of people unaware of their seropositivity decreased,¹⁰ as a consequence increasing the number of individuals who can be treated quickly and reducing the spread of infection.

People who are possibly contaminated are given anti-retroviral drugs for four weeks to prevent the development of HIV infection.³
In spite of some interesting results, research of vaccines is not currently successful¹¹ but some ways of pre-exposure prophylaxis have been shown to be efficient and safe in clinical trials, for example daily uptake of Truvada (Tenofovir Disoproxil Fumarate + emtricitabine).¹²

Since the 1990’s, the therapeutic arsenal has been dramatically increased. Currently there are more than 20 antiretroviral drugs divided into six classes: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), CCR5 antagonists⁸, and integrase strand transfer inhibitors (INSTIs).^8,13
The treatment typically consists of drug combinations depending on infection stage, patient and previous treatment.⁸

Drug resistance (virus can replicate despite use of antiretroviral drugs) has appeared. Two types of HIV drug resistance exist: acquired (mutation resistance) and transmitted (person is infected by resistant HIV). Transmitted HIV drug resistance, especially to non-nucleoside reverse transcriptase inhibitors, is increasing in low and middle-income countries.⁶ Fortunately, when first-line treatment is no longer efficient, second-line treatment combination seems effective in most cases.⁶

References

1. Gallo R. C. et al. The Discovery of HIV as the Cause of AIDS. N Engl J Med 2003; 349:2283-2285.
2. Barroso H. et al. Evolutionary and Structural Features of the C2, V3 and C3 Envelope Regions Underlying the Differences in HIV-1 and HIV-2 Biology and Infection. PLoS One. 2011; 6(1): e14548.
3. Beers M.H. et al. The Merck manual of medical information. Merck research laboratories. Second home edition. 2003, 1168-1184.
4. World Health Organization. Global Health Sector Strategy on HIV/AIDS 2011-2015. Edition 2011.
5. UNAIDS. Global Report: UNAIDS Report on the Global AIDS Epidemic 2010. Available at: http://www.unaids.org/globalreport/Global_report.htm, accessed the 1st of August 2012
6. World Health Organization. HIV Drug Resistance Report 2012. Available at: http://apps.who.int/iris/bitstream/10665/75183/1/9789241503938_eng.pdf, accessed the 1st of August 2012
7. Didiqu C. A. et al. Novel Approaches to Inhibit HIV Entry. Viruses. 2012 February; 4(2): 309–324.
8. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf , accessed the 1st of August 2012
9. Smith D. K. et al. Male Circumcision in the United States for the Prevention of HIV Infection and Other Adverse Health Outcomes: Report from a CDC Consultation. Public Health Rep. 2010; 125(Suppl 1): 72–82.
10. Lasry A. et al. Allocating HIV Prevention Funds in the United States: Recommendations from an Optimization Model. PLoS One. 2012; 7(6): e37545.
11. Reynell L. et al. HIV vaccines: an attainable goal? Swiss Med Wkly. 2012;142:w13535
12. Heneine W. et al. HIV Prevention by Oral Preexposure Prophylaxis. Cold Spring Harb Perspect Med. 2012 March; 2(3): a007419.
13. Quashie P. K. et al. Novel therapeutic strategies targeting HIV integrase. BMC Med. 2012; 10: 34.