HIV Medications and Treatments

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HIV Medications and Treatments

Abstract

The Human Immunodeficiency Virus (HIV) is an intelligent as well as remarkably complex microbe. It weakens the immune system as it progresses and eradicates crucial lymphocytes such as T-Cells or CD4 cells. It renders the body useless against fighting other infections such as Mycobacterium tuberculosis. HIV is commonly transmitted through infected blood via unprotected sexual contact such as anal sex or oral sex, but it can be contracted through contaminated needles and such.

Acquired Immunodeficiency Syndrome (AIDS) is the final stage of infection in which the body’s CD4 count lowers to a staggering 200 cells/mm³. AIDS develops when CD4 cells can no longer be replenished at the rate they are destroyed. This final stage is especially complicated as cancers such as cervical, non-Hodgkin lymphoma, and Kaposi sarcoma can develop.

Infections caused by other bacteria and parasites are also common at this stage, since the immune system has been thoroughly suppressed. As of December 2012, an estimation of 34 million people worldwide are living with HIV/AIDS, while an estimated 2 million (precisely 1.7 million) of them have perished. HIV/AIDS itself is an interesting subject, but far more captivating are the medications constructed to suppress its advancements as well as how different cultures “treat” this disease.

Key Words:

HIV/AIDS, CD4 cells, ART, HAART, AZT + 3TC/Combivir, Interferon

Introduction

Although a cure has not been discovered for HIV/AIDS there are many treatments/ medications capable of slowing its progression such as antiretroviral therapy, highly active antiretroviral therapy (HAART), AZT + 3TC, and Interferon. These are the most commonly known to make an impact on infected individuals, but they are far from perfect. Antiretroviral therapy has been extolled as the most effective way of suppressing the disease. It is efficacious in lowering viremia in the blood stream as well as lowering the HIV replication to undetectable levels.

Highly antiretroviral therapy, although similar to ART is much more aggressive as it uses a combination of three or more drugs to delay the progression of the virus. HAART must be consumed every single day, which heavily impact the liver. AZT + 3TC is a combination drug also known as Combivir. It is part of the ART regiment, though its efficiency has been highly debated since it has egregious side effects. Interferon is a protein naturally created by the body to stimulate immune function.

A synesthetic version is created in order to combat the HIV infection. HIV does impair the function the body’s natural interferon cells, but at a large dose it may aid in suppressing the replication of the virus. Towards the end of this paper the treatment of HIV according to four different cultures will be discussed such as the African-American, Chinese, South African, and Western European culture.

Antiretroviral Therapy (ART)

Antiretroviral therapy is a combination of different prescription drugs to combat the replication of the HIV virus. Its main intent is to reduce viremia, decrease plasma in viral load as well as suppress replication of the virus. More than 31 drugs are available and they impede different stages of the viral replication process, which allows them to weaken the advancements of the virus—but they cannot fully eliminate it from the body.

There are four different categories/classes of medications—Nucleoside and Nucleotide reverse transcriptase inhibitors (NRTIs), Non-nucleoside reverse transcriptase inhibitors (NNRTIs), Protease inhibitors (PIs) and fusion inhibitors and CCR5 antagonists (which inconvenience viral entry). The death toll of HIV/AIDS has been drastically reduced due to antiretroviral therapy, “A growing group of researchers and public officials have suggested that 1or more ART drugs may be useful not only in clinical benefits to individuals, but also in decreasing HIV transmission globally.” (Mayer, MD, Venkatesh, PhD, 2010)

Antiretroviral therapy has many benefits including “reducing mother to child transmission,” ((Mayer, MD, Venkatesh, PhD, 2010) by decreasing viral load (due to the fusion inhibitors and CCR5 antagonists) in the mother’s body. Antiretroviral therapy also increases the life expectancy of those with a CD4 cell count of less than 200, as the disease progresses. As the concentration of HIV virus in the blood lessens, the CD4 cells count increases—which in return increases life expectancy, as the immune system gradually improves.

It is beneficial when administered during the later stages of the infection as opposed to during primary infection, which greatly benefits those who detected the disease during its later stages. It has also become increasingly accessible and much more affordable (depending on the patients insurance coverage and income). Antiretroviral therapy also reduces viral load in the genital tract, which reduces the chances of serodiscordant sexual transmission.

Although, antiretroviral therapy has many benefits, it also has many disadvantages. For instance, due to the different combination of drugs, antiretroviral therapy can lead to liver related injuries, “liver diseases are the leading causes of death in human immunodeficiency virus (HIV)–positive persons since the widespread use of antiretroviral treatment.” Prolonged exposure to ART drugs may increase hepatitis related illnesses—such as chronic hepatitis B and C infections.

Antiretroviral drug-related liver injury (ARLI) is also a huge concern of those undergoing treatment, “ARLI have been described, including metabolic host-mediated injury, hypersensitivity reactions, mitochondrial toxicity, and immune reconstitution phenomena… [And] elevations in liver enzymes in serum, with alanine aminotransferase (ALT) characteristically greater than aspartate aminotransferase (AST).” (Soriano et al., 2008)

ART is costly, especially among those who are low income and without insurance. In the United States alone, brand name antiretroviral therapy medications cost between $10, 000 to $20, 000 per patient, annually. Brand name medications are much more expensive than their Generic counterparts—which is increasingly becoming an option for those who cannot afford the treatment. The production of recent versions of brand name medications can be debilitating for low income patients as they will no longer have access to generic brands—which may hinder their treatment process.

The side effects of certain antiretroviral medications is an immeasurable disadvantage. Certain side effects may be mild compared to those of other drugs, since ART is a compilation of many medications. ART medications must be consumed daily—once a patients starts the treatment they cannot stop. If one misses a dose or multiple doses, they risk the chance of building immunity, if they choose to begin again. Medications within the Protease Inhibitors category may cause a rise in levels of cholesterol and triglycerides. The rise of blood sure and excessive complications for those with hepatic infections, is a concern of those undergoing ART.

Highly active antiretroviral therapy (HAART)

Highly active antiretroviral therapy (HAART) is much more aggressive than ART. Usually three or more medications are combined to ensure the reduction of viral load, increase in CD4 cells count, inhibit the progression to AIDS, and provide anti-viral management with ease. HAART medications must be consumed daily in order to prolong life expectancy. Due to the amount of medications combined into one product, HAART is able to delay the progression of HIV/AIDS throughout its multiple stages.

To reduce viral load, HAART hinders the HIV virus from attaching itself to CD4 cells. Once the virus attaches itself it begins to integrate into the host’s genetic material, where it will stay until it decides to become active. This entire process of integration is hindered by fusion inhibitor medications. The less CD4 cells HIV is unable to attach itself to, the better the immune system can repair itself. HAART also inhibits the alteration of CD4 cells through the use of integrase inhibitor medications. Lastly, it prevents the reproduction of HIV viruses inside cells through the use of Nucleoside and Nucleotide reverse transcriptase inhibitors (NRTIs), Non-nucleoside reverse transcriptase inhibitors (NNRTIs), and Protease inhibitors (PIs).

Due to HAART’s ability to affect different stages of HIV replication, patients diagnosed in the primary stages of HIV are able to delay the infections advancement to AIDS. As CD4 cells count increases, the progression to AIDS gradually decreases—allowing for the increase of life expectancy. Anti-viral management increases as a result of HAART’s multi-class/category drug combinations. Managing and living with HIV/AIDS becomes feasible through the use of highly active antiretroviral therapy.

However, the benefits of HAART compared to its disadvantages, has many wondering whether the therapy is worth it. HAART can cause hepatotoxicity, hyperlipidemia, lipodystrophy, and lactic acidosis. Hepatotoxicity (liver damage) is caused by an increase in liver enzymes in the blood. Once the liver becomes damaged, these enzymes are released into the blood stream, causing nausea, vomiting, abdominal pain, diarrhea, jaundice, and hepatomegaly.

Hepatotoxicity is mostly caused by Nucleoside and Nucleotide reverse transcriptase inhibitors (NRTIs) as well as Non-nucleoside reverse transcriptase inhibitors (NNRTIs). Hyperlipidemia is an increase in the amount of cholesterol and triglycerides in the blood. If left untreated it may progress to pancreatitis and heart disease. It is mostly caused by some protease inhibitors, which can raise lipid concentration in blood. Hyperlipidemia is especially dangerous as it does not have apparent symptoms. In order to detect, one has to undergo laboratory test. Once it becomes evidently severe, individual will cease to continue HAART.

Lipodystrophy is a disruption of how the body distributes, produces, uses, and stores fat. There are two different kinds of lipodystrophy—lipoatrophy and hyper-adiposity. In lipoatrophy, fat is wasted in the visage arms, legs, and buttocks, giving those with the disease a gaunt and hollow appearance. In hyper-adiposity, fat will often accumulate in the back of the neck, upper shoulders, abdomen, and breasts (for both men and woman). Lipodystrophy can cause multiple metabolic disorders such as hyperglycemia and hyperlipidemia. They are all including, lipodystrophy mostly caused by NRTIs and protease inhibitors. Body fat changes in body, MRI and CT scans are used to detect lipodystrophy in those on HAART.

Lastly, lactic acidosis, a potentially life threatening condition caused by excessive lactate and increasing acidity in blood (low blood pH). NRTIs disrupt the function of the mitochondria, which in return produces excessive lactate. Despite its many side effects, HAART is beneficial to most patients—providing virological suppression of HIV/AIDS as well as increasing life expectancy.

AZT + 3TC

AZT+3TC is a combination of two drugs—Zidovudine (AZT) and lamivudine (3TC). Together they are also known as Combivir—a significant part of antiretroviral therapy and HAART. Combivir is one of the many Nucleotide reverse transcriptase inhibitors (NRTIs). Similar to ART and HAART it lowers viral load, increases the CD4 cells in the body, and helps patients avoid opportunistic infections and cancers caused by HIV. It stops the virus from replication, which in return inhibits the virus from infecting other cells in the immune system.

Once the HIV is inside the CD4 cells it begins to replicate. The viral multiplication is accomplished through the conversion of the HIV virus genetic material from RNA to DNA. This process is achievable due to the enzyme, reverse transcriptase. AZT+3TC blocks the reverse transcriptase enzyme, disrupting the HIV replication process, thus lowering viral load and increasing CD4 cells. AZT+3TC has been extolled for lowering prenatal and perinatal HIV transmission.

Nevertheless, AZT+3TC has some of the most severe side effects of NRTIs. It has been linked to anemia, granulocytopenia, myopathy, and neuropathy. Anemia occurs in about 70 to 80% of those afflicted with HIV/AIDS due to drug therapy, autoimmune suppression, etc… AZT+ 3TC exacerbates anemia as it causes myelosuppression—the decrease in the production of cells providing immunity such as leukocytes, erythrocytes, and thrombocytes.

“The anemia reported in patients with advanced HIV disease receiving AZT appeared to be the result of impaired erythrocyte maturation as evidenced by macrocytosis while on drug.” (ViiV Healthcare, 2014) Anemia occurring during the usage of AZT+ 3TC was much more common in those in the later stages of HIV/AIDS rather than the primary stages, “The use of AZT can cause bone marrow suppression which may present as anaemia or neutropenia. This anaemia is more common in late-stage HIV disease.”(Orrell et al., 2011).

Granulocytopenia is the decline of granulocytes (a type of white blood cell). It occurs when the count of granulocytes declines below 500 cells/mm³. The risk of attaining sepsis and infections is significantly higher in patients with granulocytopenia. Symptoms include chronic viral, bacterial, and fungal infections, skin abscesses, splenomegaly (enlarged spleen), pneumonia or bronchitis, and many others. AZT+ 3TC most often causes granulocytopenia than any other NRTI. In order to detect AZT+3TC induced granulocytopenia, a bone marrow test as well as blood cell count well be conducted.

Myopathy is characterized by muscle weakness (due to dysfunction of muscle fibers), myalgia (pain in muscle), and the most severe form—muscle wasting. Nucleotide reverse transcriptase inhibitors (NRTIs) have been linked as the causation of myopathy in patients using AZT+3TC. Neuropathy is characterized by pain and numbness in a single nerve or multiple nerve sets.

Patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy. Zi-dovudine (AZT) causes myopathy; zalcitabine (ddC), didanosine (ddI) and lamuvidine (3TC) cause neuropathy… In vitro , NRTIs inhibit the gamma-DNA polymerase, responsible for replication of mtDNA, and cause mtDNA dysfunction. In vivo , patients treated withAZT, the best studied NRTI, develop a mitochondrial myopathy with mtDNA depletion, deficiency of COX (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion, as determined with in vivo MRS spectroscopy, due to impaired oxidative phosphorylation (Dalakas, M. C.,2001).

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