The Pathophysiology of HIV/Aids

HIV and AIDS remains one of the most significant public health concerns of this generation. The virus spreads through the body via the body fluids like blood and vaginal fluids thereby, weakening the immune system. The main target of the virus is the CD4 cells which are the cells that protect the body against infections. While the body tries to make more cells or limit their influence, they finally become overpowered.

While significant progress has been made in reducing the incidence of HIV and AIDS and the deaths, the number of people living with the virus has increased over the years because of the high number of people using antiretroviral treatment. This analysis has established that the medication of the HIV using antiretroviral drugs has reduced the pain and condition of the disease from fatal to a manageable condition. This study established that the efficacy of the ART in treating HIV-1 is highest if the treatment is begun when the viral load is high.
Key Words: HIV, AIDS, pathogenesis, Transmission Antiretroviral, CD4 cells

Introduction

The human immunodeficiency virus (HIV) is thought to have mutated to a virus that infects humans from one that infected chimpanzees in the 1970s to early 1980s (Maartens, Celum, & Lewin, 2014). The virus causes disease by attacking the immune cells and overwhelming the system over time. When not treated, the infection causes symptoms within 8 to 10 years after attacks of opportunistic diseases. This phase where the symptoms manifest is referred to as acquired immune deficiency syndrome (AIDS). Currently, the HIV is an enduring infection which is, however, treatable and controllable with the use of medications. 

The most current statistics show that since the beginning of the epidemic, more than 40 million people have succumbed to AIDS while a further 38 million are living with the HIV (World Health Organization, 2010). While the HIV infection is a global epidemic, the sub-Saharan Africa region is the most severely affected region accounting for nearly 70% of new infections in the world (Maartens, G., Celum, & Lewin, 2014). The most prominent means of transmission of the disease is heterosexual intercourse which accounts for 85% of global transmission. It has also been established that almost one half of the world population of people living with HIV are women. In the United States, almost 60% of new diagnoses are attributed to male-to-male sexual activities. Moreover, heterosexual intercourse is responsible for 25% of new diagnoses and the intravenous drug use accounting for the remaining 15% (World Health Organization, 2010). The US has seen sustained reduction of infection among the women and the children mainly because of sustained testing and treating of the infected mothers.

The infection occurs in three stages which if not treated worsen and overcome the immune system (Maartens, Celum, & Lewin, 2014). The first stage is the acute HIV infection which happens within two to three weeks of infection. The phase is characterized by symptoms similar to those of other diseases and may be compared to flu. The most common ones include headache, nausea and vomiting, fatigue, headache, sore throat, swelling of lymph nodes, fever, aching muscles and an itch-less red rash at the torso (Rubinstein, Aboulafia, & Zloza, 2014). The second stage, chronic HIV infection, is a period when the acute stage symptoms disappear. This stage is also called the asymptomatic stage and many people may not realize they are infected until they are tested (Cohen, et al., 2016). During this stage, the virus will be CD4T cells and weakening the immune system. AIDS is the last and advanced phase of the infection. This stage occurs after the total count of the CD4-T cells falls below 200 (Rubinstein, Aboulafia, & Zloza, 2014).

Literature Review

The HIV-1 pandemic presents a sophisticated mix of various epidemics within nations and countries of the world. Indeed, the pandemic has been the undoubtedly most significant public-health concern of this generation. However, with research, people have been presented with the knowledge of the replication, manipulation and how the virus hides in the human body of an infected person (Cohen, et al., 2016). While this understanding of the pathogenesis and modes of transmission have been of immense importance in expanding the prevention efforts, a cure  or a vaccine is yet to be established, almost four decades since the infection was discovered. Some of the benefits of the research have been the discovery of the antiretroviral medication that has altered the AIDS from a deadly disease to a more manageable condition.

With the increase in the uptake of antiretroviral treatment, the HIV prevalence has been on the increase.  Maartens, Celum, and  Lewin, (2014) argue that this phenomenon can be explained by the fact that people under antiretroviral live longer. The infections rates have been in the decline from the high of 3.3 million in 2002 and getting to 2.3 million by the end of 2012. In 2005, there were 2.3 million global deaths resulting from AIDS-related illnesses which decreased to 1.6 million in 2012. Antiretroviral therapy had been uptaken by more than 9.7 million people in poor countries by the year 2012 (Maartens, Celum, & Lewin, 2014). Increased recognition is being directed to the role of immune activation in understanding the pathogenesis of clinical events not related to AIDS. Some of the key prevention breakthroughs that have been made and which are vital to public health include medical circumcision of males, use of antiretroviral therapy in preventing transmission of the virus from the mother to the child and for pre-exposure prophylaxis (Cohen, et al., 2016). Significance progress has been made into other prevention methods including vaccines and vaginal microbicides (Maartens, Celum, & Lewin, 2014).

Pathogenesis

The infection of HIV and its progression is determined by the viral phenotype and effective entry of the virus (Maartens, Celum, & Lewin, 2014).  Through the CD4+ molecules, the virus gets attached to and penetrates the host T cells. The virus then releases HIV RNA and other encoded enzymes into the host cell. To end the viral replication, a reverse transcriptase is required to copy the HIV RNA to produce a proviral DNA.  However, this mechanism of copying is not perfect and results to errors of frequent mutations. The consequence is that the HIV with the ability to resist control of the immune system of the host is facilitated by the mutations (Cohen, et al., 2016).

The proviral DNA penetrates the nucleus of the host cell where it is integrated to the DNA of the host cell with the help of an HIV enzyme called integrase. For any single cell division, the proviral DNA integrated into the host DNA gets the same duplication. The result of this process is the transcription of the proviral DNA to HIV RNA and transformed into HIV proteins. The proteins, including glycoproteins 41 and 120, together form HIV virions at the inner cell membrane of the host cell with subsequent budding from the cell surface. The host cells produce thousands of virions (Maartens, Celum, & Lewin, 2014). After budding, the viral proteins are cleaved by enzyme protease and in the process convert the immature virion into an infectious virion. 

The HIV virus attacks the CD4-T cells. While the body attempts to respond by seeking to contain the virus or making of new T cells, the virus wins the battle and eventually succeeds in destroying the ability of the body to fight other infections and illnesses (Rubinstein, Aboulafia & Zloza, 2014).  There are a number of ongoing studies seeking to establish the structure of the virus. Some of the benefits of these studies include the development of new drugs to manage HIV. 98% of the plasma virions are produced by the infected CD4 white blood cells. When treatment with antiretroviral medication is stopped, a reservoir of HIV contained in the CD4 lymphocites that have been infected may reactivate rapidly (Cohen, et al., 2016).

Treatment and management of the disease is currently done through the use of antiretroviral medication. A variety of studies have attempted to either establish the efficacy of the ART in managing HIV-1 infection. One study conducted by Lee, Amin, and Carr (2014) sought to determine the effectiveness of the initial ART in adults infected by HIV-1. The study used a systematic review and a meta-analysis approach of 114 primary researches that had up to 144 follow-up. The outcome measures included the efficacy of the ART and the premature cessation of the therapy. The study concluded that there is suboptimal efficacy for the initial ART for HIV-1. However, the treatment is more efficacious if it is begun when the viral loads <100,000 copies/mL. In other words, the rise in the viral road is an indicator of starting the treatment. 

Treatment of the disease has failed in several attempts due to the emergence of drug resistance. This has posed big problems both clinically and public health problems.  Drug resistance mode is a result of different HIV subtypes. These subtypes pose different modes of mutations that lead to drug resistance (Rubinstein, Aboulafia & Zloza, 2014). Another means leading to drug resistance is the fact that there are naturally occurring polymorphisms. A significant finding coming out from Lee, Amin, and Carr (2014) study is the advantage of the integrase inhibitors compared to other classes of drugs. A study by Maraolo (2017) that sought to upgrade the literature regarding the resistance to HIV-1 integrase inhibitors consider these drugs as being the most significant drugs in the third element of the three-agent regimen. The integrase strand transfer inhibitors present a pillar of simple therapeutic schemes. However, Maraolo (2017) notes that a risk of the occurrence of resistance that may thwart the efforts of doctors to employ the use of this drug as a treatment of HIV-1. He argues that an insight into the means that the resistance develops is necessary to allow continued and successful use of these drugs.

Prevention

Prevention of this contagious disease is based on the mode of transmission. Main target of prevention interventions is to reduce human health behaviour that may lead to contraction of the disease. Such modes of transmission are mother-to-child transmission, sexual transmission, and transmission through drug injection.
Heterosexual intercourse has been for a long time, the most prominent means of transmitting the virus. In the United States and central Europe, men that have sex with other men have been found to have the highest rates of transmission (Cohen, et al., 2016). The prevention campaigns advocated seek to encourage people to encourage people to change their sexual behaviour by being faithful to their partners, using condoms for sexual intercourse where necessary and abstaining from risky sexual behaviours (Akala & Semini, 2010). These options are combined and together referred to as ABA approach. 

Mother to child transmission is another method that helps transfer the virus. This transfer happens during childbirth, pregnancy and during breastfeeding. A variety of interventions have been put forward to counter the transmission through this mode (Wang, et al., 2015). Some of these are giving one dose of nevirapine to a newborn baby and the mother as well as the use of caesarean section as an alternative mean of delivery. Virus transmission can be transmitted from mother to child during breastfeeding, and therefore, to prevent this; it is highly recommended to use another feeding method when the mother is found to be HIV positive (Cohen, et al., 2016). An example of such replacement feeding is the use of formula feeding and replacing breastfeeding with an abrupt weaning.

Drug use and addiction presents one of the growing challenges to the transmission of the HIV. It was found that cases of HIV transmission are through the use of needles to deliver drugs to patients (MacArthur, et al., 2014). This was observed especially in under-developed countries where needles for injection are shared from one patient to another. The claim that sterilization was being undertaken was not enough for prevention because little time was provided for the process of sterilization (MacArthur, et al., 2014). One of the solutions that to this problem include the enactment of a law that provides for the use of one needle for injection is to be used for only one patient and therefore no sharing. 

Public health laws and policies concerning HIV/AIDS

Every country has laws and policies to regulate the conduct of the citizenry. For instance, countries have laws and policies concerning HIV/AIDS which help protect patients from contracting the virus. The regulations further seek bar infected individuals from knowingly exposing or infecting other members with the HIV.

Countries have enacted legislations that seek to end discrimination of patients infected with HIV or suffering from AIDS. Many national constitutions prohibit discrimination of individuals by HIV status. Studies (Wang, et al., 2015; Maartens, et al., 2014) show that there is a widespread discrimination of patients with HIV from accessing medical services such as health insurance services. This has been observed in most parts of Africa, Europe, North America and Asia (Akala, & Semini, 2010).These discriminations are among the significant barriers to prevention of the disease. The international human rights law in 2006 reported that almost 61% of countries have laws and policies that protect HIV positive persons against any form of discrimination. 

Reproductive and sexual health care and services

A majority of countries have laws and policies that seek to provide for the protection of the rights of people to access preventive medical services. For example, methods of prevention such as the use of male and female condoms are made available to every person to prevent further spread of the disease (Maartens, Celum, & Lewin, 2014). The law is important because proper and consistent condom use reduces the risk of disease transmission. However, reports show that some countries make condoms available while others restrict the availability by failing to allocate funds for the same. 

Pregnant women have a right to receive health services that protect their health and that of the foetus. The World Health Organization provides that expectant women are supposed to get access to services like prenatal counselling and care, family planning services, abortion services, professional delivery care and postpartum HIV counselling and treatment for the mother and the child (Joint United Nations Programme on HIV/AIDS & UNICEF. 2010).  Although these laws are guaranteed, some countries exempt a few of them like abortion services.  
Gender-based sexual violence including harassment and rape of women, children and the vulnerable members of the community is one of the many risk factors that contribute to the spread of the infection. During such circumstances, the victims are powerless and defenceless and lack the opportunity to protect themselves against the transmission of the virus (Cohen, et al., 2016). Most countries, therefore, have passed laws against gender violence aimed at protecting women and other vulnerable members of society. The laws criminalise actions like prostitution, rape and sexual harassment, with heavy penalties imposed for any breach ((Maartens, Celum, & Lewin, 2014).

Conclusion

HIV and AIDS present one of the main challenge to public health of the late 20th century and the early part of this century. While the deaths resulting from AIDS have dramatically reduced over the last two decades, the number of people living with the infection has remained relatively stable. The paper has looked at the methods of entry into the T-cells and the subsequent modification and weakening of the body to other opportunistic illnesses. The use of ART has contributed to the successful management of the condition like any other chronic illness; something that was not the case a couple of decades ago. The ART has been one of the most significance discoveries from the various researches into the virus. The studies reviewed revealed ART is efficacious especially when the viral load is high and hence indicating when the treatment should be started. The paper also discussed the various prevention methods and challenges facing the efforts to prevent the spread of HIV. Among the identified prevention measures range from legislation, policies, campaigns and provision of basic health care services.

References

Akala, F. A., & Semini, I. (2010). Characterizing the HIV/AIDS epidemic in the Middle East and North Africa: time for strategic action. World Bank Publications.

Cohen, M. S., Chen, Y. Q., McCauley, M., Gamble, T., Hosseinipour, M. C., Kumarasamy, N., ... & Godbole, S. V. (2016). Antiretroviral therapy for the prevention of HIV-1 transmission. New England Journal of Medicine, 375(9), 830-839.

Lee, F. J., Amin, J., & Carr, A. (2014). Efficacy of initial antiretroviral therapy for HIV-1 infection in adults: a systematic review and meta-analysis of 114 studies with up to 144 weeks' follow-up. PloS one, 9(5), e97482.

Maartens, G., Celum, C., & Lewin, S. R. (2014). HIV infection: epidemiology, pathogenesis, treatment, and prevention. The Lancet, 384(9939), 258-271.

MacArthur, G. J., van Velzen, E., Palmateer, N., Kimber, J., Pharris, A., Hope, V., ... & Rhodes, T. (2014). Interventions to prevent HIV and hepatitis C in people who inject drugs: a review of reviews to assess evidence of effectiveness. International Journal of Drug Policy, 25(1), 34-52.

Maraolo, A. E. (2017). HIV-1 Integrase Inhibitors Resistance: Update of the Current Literature. Current Treatment Options in Infectious Diseases, 9(1), 44-51.

Rubinstein, P. G., Aboulafia, D. M., & Zloza, A. (2014). Malignancies in HIV/AIDS: from epidemiology to therapeutic challenges. AIDS (London, England), 28(4), 453. 

Wang, H., Wolock, T. M., Carter, A., Nguyen, G., Kyu, H. H., Gakidou, E., & Coates, M. M. (2016). Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015: the Global Burden of Disease Study 2015. The Lancet. HIV, 3(8), e361-87.

World Health Organization. (2010). HIV/AIDS surveillance in Europe, 2009. European Centre for Disease Prevention and Control.