Chapter 36 Human immunodeficiency virus
AETIOLOGY
Human immunodeficiency virus (HIV; see Figure 36.1) is the infective agent behind the spectrum of symptoms involving the immune system and leading to the diagnosis of the acquired immunodeficiency syndrome (AIDS).1 HIV attacks cells that have CD4 markers on their surface, most particularly T4 lymphocytes, also known as helper T cells. Helper T cells are the part of the immune system responsible for alerting the body to infection. Subverting these cells, the retrovirus avoids detection and uses the helper T cells to produce more HIV, leading to a greater viral load in the body. Initial infection produces a flu-like illness that is self-limiting and non-specific for HIV, so it often goes undiagnosed.2 Symptoms may include night sweats, weight loss, fever and swollen lymph nodes. HIV infection then enters a latent stage that may last upwards of 10 to 20 years. As the lymphoid tissue and the T-cells get destroyed by HIV, AIDS may be diagnosed if the CD4 count is less than 200 copies/mm3. Symptoms at this point are usually due to the effects of opportunistic infections that take advantage of the inability of the body to combat invasion.3
RISK FACTORS
The greatest risk factor that currently predisposes an individual to contracting HIV is gender. Women and girls comprise the fastest-growing population of seropositive individuals in the world.4 Anatomically this is due to the greater surface area of genital mucosa exposed to HIV-positive body fluids. Current World Health Organization estimates state that 50% of all HIV-positive individuals are female, a huge rise from the formerly male-dominated population of just a few years ago.5 The highest occurrence of HIV worldwide is in sub-Saharan Africa, which currently reports 35% of new infections and 38% of AIDS deaths.6 High-risk activities that may increase exposure to HIV include any activity in which body fluids may be exchanged, including injection drug use, blood transfusions and unprotected sexual activity. It is also possible that pregnant women may pass HIV to their fetus during the pregnancy or birth and potentially while breastfeeding.7
CONVENTIONAL TREATMENT
Conventional medications are constantly evolving, and the prescribed drugs change often, depending upon the most recent research in this dynamic field. The aim of primary therapy is to increase CD4 count and to reduce the viral load down to an undetectable level. The most popularly prescribed agents for this task are grouped under the heading of highly active antiretroviral therapy (HAART) and include drugs from several classes.8
Each of these prescriptions works to target specific sites critical to the viral replication pathway. The most common classes of drugs include nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), which insert faulty messages into the reverse transcriptase process; non-nucleoside reverse transcriptase inhibitors (NNRTIs), which bind to reverse transcriptase and halt the production of viral DNA; protease inhibitors (PIs) which are responsible for targeting the construction of new HIV; and fusion inhibitors, which block binding of the virus to the cell. Often prescribed alongside these drugs are agents to combat the systemic effects of HIV, including lipid-lowering agents, antidepressants and sedatives.9
KEY TREATMENT PROTOCOLS
Optimise digestion and liver function
Common side effects of HIV and HIV medications can include a spectrum of gastrointestinal (GI) disorders, including diarrhoea, nutrient malabsorption, abdominal pain, GI bleeding and hepatomegaly.10 Malnutrition and wasting are hallmarks of HIV infection,11 making the need for optimal digestion critical for all individuals diagnosed with HIV. Opportunistic infections of the GI may also compound these symptoms and can seriously impact quality of life.12 Supporting the gut in optimal functioning and promoting nutrient absorption can greatly improve an individual’s ability to cope with the stresses of HIV.13 Nutrients that support the gastric and intestinal mucosa include L-glutamine, probiotics and dietary fibre.14
Reducing mitochondrial toxicity
Although the drugs prescribed to combat HIV infection can greatly improve the quality of life of people living with HIV, mitochondrial toxicity is a problematic side effect regularly observed with NRTI therapy.15 Lipodystrophy (LD) is a disorder of metabolism that cause fat deposition in atypical sites, causing fat loss in the limbs and face, and excess fat deposits on the trunk. The appearance of thin limbs and wasted face combined with abdominal obesity are often seen as identifying stigma for medicated individuals. In addition to the physical appearance, mitochondrial toxicity is also responsible for the intense fatigue present in some patients. Mitochondrial toxicity combined with the effects of increased cellular oxidation causes an accelerated rate of ageing and an increase in the risk of age-related comorbidities.16 Additional effects of mitochondrial toxicity have been found to include lactic acidosis, pancreatitis and peripheral neuropathy.17 Treatment of these side effects can slow the progression of adverse events and can greatly improve quality of life for individuals on NRTIs. Supplements that can reduce mitochondrial toxicity include coenzyme Q10, riboflavin and thiamine.18 It has been noted that the levels of coenzyme Q10 are lower in individuals with advanced HIV, and that supplementation improves biochemical markers of health.19 Supplements that can function as antioxidants, immune stimulants and can aid in the treatment of mitochondrial toxicity are highly efficacious and include N-acetyl cysteine, L-glutamine, L-carnitine and alpha-lipoic acid.20 By acting as a sulphur donor, N-acetyl cysteine normalises lymphocyte glutathione production and thereby decreases the number of free radicals produced by the cell. This normalisation leads to improved CD4 levels and decreases progression to AIDS in clinical trials.21–23
Glutamine deficiency is prevalent in HIV infection as it serves as the preferred fuel for lymphocytes, macrophages and enterocytes and, since it is primarily stored in muscle tissue, a deficiency exhibits as muscle wasting and overall weight loss.24 It has been shown that supplementation at 40 g daily can reverse muscle wasting in HIV and increase weight gain in patients suffering from wasting syndrome.25
L-carnitine acts as an antioxidant and aids the production of energy by supporting the mitochondria and decreasing oxidation. Studies show that L-carnitine has an analgesic effect in the treatment of HIV peripheral neuropathy and can also improve peripheral nerve function by supporting several mechanisms, including nerve regeneration.26 Alpha-lipoic acid is also used to support glutathione levels in the blood and therefore decrease free radical activity generated by HIV infection. One study demonstrated that 300 mg t.i.d. normalised blood glutathione and increased lymphocyte reactivity to T-cell mitogens.27 In addition, alpha-lipoic acid had been used with success to treat the peripheral neuropathy of HIV by decreasing oxidative stress and inflammation of the involved nerves.28
Nutrient deficiencies
The elevated oxidation of cells in HIV infection, the side effects of therapeutic drugs and the increased stress on the body lead to the accelerated use of nutrients and subsequent deficiencies. Working to stay ahead of nutritional requirements is an integral part of treating individuals with HIV. Glutathione deficiency is a key source of immune dysfunction, muscle wasting and cellular oxidation as measured in multiple studies, but is not absorbable by the target tissues as a raw material.22 Rather, the production of glutathione must be supported by precursors, which include glutamine and cysteine. Selenium, alpha-lipoic acid27 and tryptophan are also important in increasing intracellular glutathione levels. Activities such as smoking,29 excessive exercise and drinking excessive alcohol30 can further deplete glutathione, so reducing exposure may, along with supplementation, lead to improved intracellular glutathione levels. Enhanced glutathione levels can lead to significant improvement in physical and quality of life markers, but research suggests that the benefits are present only while supplementation continues.31 It has been observed that gastrointestinal issues common in HIV may exacerbate nutrient deficiencies via malabsorption. Vitamin B12, vitamin A, beta-carotene, zinc, selenium and folate may all be affected by decreased transit time, dysbiosis and gut inflammation due to HIV or HAART.32 Antioxidants are also used at an increased rate in HIV, leading to the depletion of vitamin A, vitamin E and vitamin C.33 Supplementing these nutrients, along with other antioxidant compounds, has been shown to improve lymphocyte proliferation and apoptosis.34 Some research has been done with varying probiotic strains, but little clinical data exist to support their use in the general HIV population. Theoretically, introducing bacteria into an immunocompromised system may be harmful, and the benefits of supplementation should be carefully weighed against the inherent risk of infection.35,36 Minerals are also depleted through various mechanisms involved in HIV pathogenesis. Supplementation with minerals such as zinc,37 selenium,38 magnesium and copper39 have been shown to improve health outcomes and aid other nutrients in antioxidant functions.
Medication side effects
HAART is a life-saving intervention that can prolong an individual’s life, improve CD4 count and decrease viral load.40 Unfortunately these benefits often come at a physical price (see Table 36.1 and Figure 36.2). From liver toxicity and chronic diarrhoea, to insomnia and lipodystrophy, the symptoms are varied and can be so severe that people will stop taking the medications just to avoid the side effects. The primary target of naturopathic therapy is often the large number of adverse reactions to drugs. Making individuals more comfortable while they undergo therapy and stabilising their digestion, mood, sleep and cardiovascular health can have a profound influence upon quality of life and ultimately survival.
Table 36.1 Common side effects of HIV medications41
| MEDICATION | COMMON SIDE EFFECTS |
|---|---|
| Nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors | Lactic acidosis, hepatitis, pancreatitis, anaemia, lipoatrophy |
| Protease inhibitors | Increased cholesterol and triglycerides, diabetes, lipodystrophy and lipoatrophy, osteoporosis and osteonecrosis |
| Fusion inhibitors | Pain at injection site, rashes, bad taste in mouth, increased occurrence of pneumonia |
Cardiovascular risk
HIV not only affects the immune system, but it also has a considerable effect upon metabolism and in turn the cardiovascular system, and has been found to contribute to arteriosclerosis in infected individuals.42 Protease inhibitors, NNRTIs or both are also contributing factors in developing cardiovascular pathologies. Dyslipidaemia, blood sugar abnormalities, inflammation and decreased fibrinolysis may all increase the occurrence of adverse cardiovascular events.43 In addition to drug side effects, HIV pathogenesis has also been found to contribute to arteriosclerosis. Fortunately interventions that include dietary and lifestyle changes along with exercise can have a positive effect on lipid levels and cardiovascular markers.44 It has also been found that the use of omega-3 fish oils in combination with exercise can lead to a reduction in triglyceride levels, and would therefore be an important addition to any treatment protocol.45 In current research, another intervention that has been proven to change HIV-mediated cardiovascular markers is vitamin E.46 Acting as an antioxidant, vitamin E reduces lipoprotein peroxidation, thus decreasing the potential for damage due to elevated blood lipids. Vitamin E also acts to decrease platelet aggregation, reducing the likelihood of vessel blockage and subsequent cardiovascular events.47 In conclusion, suggesting a lower fat diet that includes high quality vegetable and protein sources, along with a moderate exercise schedule and metabolic support including fish oils and vitamin E, can help to decrease the risk of adverse cardiovascular events.
Maintaining vitality (tonics and adaptogens)
One of the greatest challenges of treating HIV is that of keeping the vital force of the patient strong. Dealing with the mental and emotional stresses, along with the physical effects of the disease, can drain an individual and decrease their ability to cope with change. Patients can get extremely overwhelmed by the volume of new information that comes with a diagnosis of HIV, and with the continued therapies involved in their care. Health maintenance becomes the main goal, and keeping physical as well as mental health balanced can be the most effective approach of all. Adaptogenic therapies can be extremely useful as an adjunct to other more aggressive medicines. The focus of adaptogenic medicines needs to be not only on supporting the adrenal glands, but also targeting the immune system. Herbs such as Withania somnifera,48 Eleutherococcus senticosus, Panax ginseng, Ganoderma lucidum and Glycyrrhiza glabra can all support the immune system while increasing tolerance to stress. Withania somnifera, in one study, was prescribed as an extract at 6 mL b.i.d. for 4 days with a result of stimulating an increase in the expression of CD4 and natural killer cells, demonstrating its stimulatory effect on the immune system.49 Eleutherococcus senticosus extracts have been found to increase CD4 counts and lymphocyte populations when used in healthy subjects.50 Studies have also shown that Eleutherococcus senticosus aids in adrenal function through decreasing adrenal hypertrophy and increasing adrenal vitamin C levels.51 Panax ginseng is a popular botanical used in traditional Chinese medicine and has demonstrated a broad range of effects on the immune system by enhancing both B- and T-cell mediated responses while acting as an antimicrobial against Heliobacter pylori and Staphylococcus aureus,52 which can lead to infection in HIV-positive individuals. In addition, one animal study found it to increase CD4 cell function against the challenge of an induced systemic candida infection,53 which is one of the main opportunistic infections found in HIV/AIDS. Ganoderma lucidum, a fungus traditionally used in Chinese medicine, has been proven to reduce physical and mental fatigue, while improving the function of the immune system.54 Glycyrrhiza glabra, as an extract, has been shown to decrease infective capability of Candida albicans strains.55 It has also been studied as a compound that interferes with the infective abilities and replication of HIV, in addition to its anti-inflammatory and adrenal support functions.56 Prescribing a botanical medicine based not only on its adaptogenic properties but also on its antimicrobial and immunosupportive qualities can help HIV-positive patients to maintain a high quality of life and improve their overall health.
Other lifestyle interventions, such as moderate exercise,57 alternating hot and cold showers58 and a daily meditation practice,59,60 also round out a treatment protocol for enhancing energy and boosting perceived quality of life.
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