Published on March 10, 2014
HIV EPIDEMIOLOGY AND PATHOGENESIS PRAKASH DHAKAL Public Health Microbiology Tribhuvan University, Nepal
OUTLINE OF PRESENTATION Epidemiology Pathogenesis Treatment and Control
EPIDEMIOLOGY : WORLD HIV, the virus that causes AIDS, “acquired immunodeficiency syndrome” has become one of the world’s most serious health and development challenges. The first cases were reported in 1981. According to the latest estimates from UNAIDS: There were 35.3 million people living with HIV in 2012, up from 29.4 million in 2001, the result of continuing new infections, people living longer with HIV, and general population growth. The global prevalence rate (the percent of people ages 15-49 who are infected) has leveled since 2001 and was 0.8% in 2012.
1.6 million people died of AIDS in 2012, a 30% decrease since 2005. Deaths have declined due in part to antiretroviral treatment (ART) scale-up. HIV is a leading cause of death worldwide and the number one cause of death in Africa. New HIV infections overall have declined by 33% since 2001 and, in 26 low- and middle-income countries, new infections have declined by 50% or more. Still, there were about 2.3 million new infections in 2012 or more than 6,300 new HIV infections per day.
Most new infections are transmitted heterosexually, although risk factors vary. In some countries, men who have sex with men, injecting drug users, and sex workers are at significant risk. Although HIV testing capacity has increased over time, enabling more people to learn their HIV status, the majority of people with HIV are still unaware they are infected. HIV has led to a resurgence of tuberculosis (TB), particularly in Africa, and TB is a leading cause of death for people with HIV worldwide. In 2012, approximately 13% of new TB cases occurred in people living with HIV. However, between 2004 and 2012 TB deaths in people living with HIV declined by 36%, largely due to the scale up of joint HIV/TB services.
Women represent about half (52%) of all people living with HIV worldwide. HIV is the leading cause of death among women of reproductive age. Gender inequalities, differential access to services, and sexual violence increase women’s vulnerability to HIV, and women, especially younger women, are biologically more susceptible to HIV. Young people, ages 15–24, account for approximately 39% of new HIV infections (among those 15 and over).Globally, young women twice as likely to become infected with HIV than their male counterparts. In some areas, young women are more heavily impacted than young men. Globally, there were 3.3 million children living with HIV in 2012, 260,000 new infections among children, 210,000 AIDS deaths, and in 2011, approximately 17.3 million AIDS orphans (children who have lost one or both parents to HIV), most of whom live in sub-Saharan Africa (88%).
Sub-Saharan Africa. Sub-Saharan Africa, the hardest hit region, is home to 71% of people living with HIV but only about 12% of the world’s population. Most children with HIV live in this region (88%).Almost all of the region’s nations have generalized HIV epidemics—that is, their national HIV prevalence rate is greater than 1%. Latin America & The Caribbean. About 1.6 million people are estimated to be living with HIV in Latin America and the Caribbean combined, including 98,000 newly infected in 2012. The Caribbean itself, with an adult HIV prevalence rate of 1%, is the second hardest hit region in the world after sub-Saharan Africa.
Eastern Europe & Central Asia. An estimated 1.3 million people are living with HIV in this region, including 130,000 newly infected in 2012. The epidemic is driven primarily by injecting drug use, although heterosexual transmission also plays an important role.. Asia. An estimated 4.8 million people are living with HIV across South/South-East Asia and East Asia. The region is also home to the two most populous nations in the world – China and India – and even relatively low prevalence rates translate into large numbers of people.
EPIDEMIOLOGY: NEPAL In Nepal, the first-ever AIDS case was reported in 1988. Ever since, the nature of the HIV epidemic in the country has gradually evolved from being a “low-prevalence” to “concentrated” epidemic. Over 80 per cent of the HIV infections are transmitted through heterosexual transmission. Prevalence is 0.30 per cent among adult aged 15–49 years in 2011. There are approximately 50,200 people estimated to be living with HIV. The prevalence of HIV infection among adult (15–49 years) males (58%) and females belonging to the reproductive age group (28%) was the highest, where as children aged under 15 years accounted for approximately 8 per cent of the total infected population in 2011.
The majority of the HIV infections among children in this age group were owing to mother-to-child transmission (MTCT). People who inject drugs (PWIDs), men who have sex with men (MSM) and female sex workers (FSWs) are the key populations who are at a higher risk of acquiring HIV. Male labor migrants (who particularly migrate to high HIV prevalence areas in India, where they often visit FSWs) and clients of sex workers in Nepal are playing the role of bridging populations that are transmitting infections to low-risk general populations. The rate of occurring new HIV infections throughout Nepal has reduced significantly during the last five years essentially owing to the targeted prevention interventions among key population groups.
PATHOGENESIS HIV primarily attach to specific receptors on host cells containing CD4 using a glycoprotein gp120. Secondary attachment occurs due to co receptor molecules ( CCR5 or CXCR4). Co receptor facilitate the tight binding of the virus to the cell membrane and induce conformational change in the viral envelope glycoproteins . Mostly helper Tcells ( TH cells) and sometimes monocytes,macrophages ,Nk cells , certain B cells and glial cells are target for HIV.
During infection , the virus infects TH cells within local mucosal surfaces infecting local lymphoid tissues. The virus quickly disseminates systemically infecting remote lymphoid tissues as well as the glial cells . Then the virus quickly appears in genital secretions. Within weeks of initial infection , virus specific cytotoxic T cells appear in the peripheral blood and lymphoid tissues. After short period , neutralizing antibodies may be detected in the plasma and virus replication process is initiated in this process.
Hosts develop an adequate immune response to the virus . However reverse transcriptase makes very high replication error ( 1 in 10000 bases copied) . So that HIV progeny virus mutates in each replication cycle ,thus HIV infected cells persists in lymph nodes. Infected cells can be killed directly by virus replication or indirectly by virus specific effector mechanisms.
After several months of infection , a balance is established among virus replication , immune effector mechanisms and cells available for virus replication , and the infection enters its chronic phase during which the patient is generally asymptomatic. Rapid viral replication is accompanied by a marked drop in the number of circulating CD4+ T cells.
99 % virus replication occurs in CD4+ T cells in lymphoid organs and 1% virus replication occurs in monocytes and resting CD4+ T cells. When CD4+ T cells decline below 200 cells/µl ,infections with variety of opportunistic microbes occur. The risk of opportunistic infections ( OIs) and malignancies are high when CD4 T cells is below 50 cells/µl . The rate of immunologic and clinical progression is directly related to the extent of virus replication and varies considerably from individual to individual.
PREVENTION AND TREATMENT Numerous prevention interventions exist to combat HIV, and new tools, such as vaccines, are currently being researched. Effective prevention strategies include behavior change programs, condoms, HIV testing, blood supply safety, harm reduction efforts for injecting drug users, and male circumcision. Additionally, recent research has shown that providing HIV treatment to people with HIV significantly reduces the risk of transmission to their negative partners and the use of antiretroviral-based microbicide gel has been found to reduce the risk of HIV infection in women. Pre-exposure antiretroviral prophylaxis (PrEP) has also been shown to be an effective HIV prevention strategy in individuals at high risk for HIV infection.
HIV treatment includes the use of combination antiretroviral therapy to attack the virus itself, and medications to prevent and treat the many opportunistic infections that can occur when the immune system is compromised by HIV. Nucleotide reverse transcriptase inhibitor (NRTIs) – block virus replication . E.g. : Zidovudine, Abacavir Protease inhibitors .E.g. Amprenavir, Indinavir HAART ( Highly Active Antiretroviral Treatment)
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