Health of HIV Infected People: Food, Nutrition and Lifestyle with Antiretroviral Drugs

By Ronald Ross Watson

Health of HIV Infected People: Food, Nutrition and Lifestyle with Antiretroviral Drugs provides basic and applied knowledge on the supportive roles of bioactive foods, exercise, and dietary supplements on HIV/AIDS patients receiving antiretroviral drugs.

Approaches include the application of traditional herbs and foods aiming to define both the risks and benefits of such practices. Readers will learn how to treat or ameliorate the effects of chronic retroviral disease using readily available, cheap foods, dietary supplements, and lifestyle changes with specific attention to the needs of patients receiving antiretroviral drugs.

This work provides the most current, concise, scientific appraisal of the efficacy (or lack thereof) of key foods, nutrients, dietary plants, and behavioral shifts in preventing and improving the quality of life of HIV infected infants and adults, while also giving the needed attention to these complex and important side effects.

• Covers the role of nutrients in the prevention and treatment of HIV-induced physiological changes in children undergoing HAART, including covers of omega-3 fatty acids, dietary fat intake, metabolic changes, and vitamin D
• Explores food and the treatment of obesity, diabetes, and cardiovascular disease in HIV infected patients, including fundamental coverage and recommendations for care
• Provides coverage of fitness and exercise regimens, physical activity, and behavioral and lifestyle changes on HIV infected individuals
• Gives careful attention to the specific nutritional needs of patients undergoing HAART therapy

• Language: English
• Publisher: Academic Press
• Release date: Apr 30, 2015
• ISBN: 9780128011430

Book preview

book.

Section I

Food and Overview

Outline

Chapter 1 Exercise and Rehabilitation: Exercise in the Era of HAART in South Africa

Chapter 2 Metabolic Abnormalities in HIV-Infected Populations without or with Antiretroviral Therapy (ART)

Chapter 3 Effects of Dietary Fat Intake on Acquired Immune Deficiency Syndrome During Antiretroviral Therapy

Chapter 4 Human Immunodeficiency Virus Infection–Associated Cancer and Mycotoxins in Food

Chapter 5 Effects of Omega-3 Fatty Acids on Body Composition and Health in HIV/AIDS During HAART Therapy

Chapter 6 Diet Modulation of Chronic Inflammation in Individuals with Acquired Immune Deficiency Syndrome

Chapter 1

Exercise and Rehabilitation

Exercise in the Era of HAART in South Africa

Sonill Sooknunan Maharaj,    University of KwaZulu-Natal, Durban, South Africa

Highly active antiretroviral therapy (HAART) for individuals with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has been in use in South Africa for the past decade. Factors such as patient compliance, side effects of medications, and availability of HAART for the increasing number of individuals being infected by the virus, as well as transition from acute to chronic illness, have made it necessary to come up with alternative forms of therapies. Exercise is one such form of therapy, but due to limitations in cardiorespiratory fitness and other pathologies, exercise must be set according to the level of fitness of the infected individual. Rebound exercise appears to be suitable for this population; it is a simple form of aerobic activity performed on a mini-trampoline, which is based on the use of an elastic surface, gravity, and springs. Individuals who cannot perform other more physically demanding exercises enjoy and cope with the bouncing or jumping activities on the mini-trampoline. This chapter explains how this exercise can benefit HIV-infected individuals receiving HAART and the physiology of exercise.

Keywords

Rebound exercise; HAART; chronic pathologies

1.1 Introduction

Highly active antiretroviral therapy (HAART) for individuals with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) with a CD4 count of less than 200 cells/mm³ was introduced in South African public hospitals in 2004 and has been in use for the past decade. HAART, which is a triple combination of antiretroviral drugs (ARVs), has changed the prognosis of AIDS from a terminal to chronic cyclical illness because the combination of drugs results in elevating the CD4 counts in infected individuals and increasing the potential to live longer [1,2]. It is estimated that more than 80% of individuals diagnosed with AIDS and receiving HAART survive for 3 years or more with a lower incidence of opportunistic infections [3,4]. However, it is reported that these infected individuals are presenting with an increase in chronic health problems, impairments, and disabilities compared with the pre-HAART era [5]. Projections in South Africa indicate that beyond 2015, the number of patients with chronic AIDS will continue to increase even with antiretroviral treatment [6]. The reason for this is that HIV infection and HIV drug therapies cause physical and psychological challenges for the patients. The physical challenges result from neuro-musculo-skeletal symptoms with neurologic manifestations. Of these, peripheral neuropathy seems to be the most common condition, followed by respiratory complications, mainly pneumonia and tuberculosis (TB). The neurologic complications may be related to studies that have documented relationships among the central or peripheral nervous system, peripheral neuropathy, and the HIV infection, in association with antiretroviral therapy [7,8]. The relationship between the antiretroviral therapy and the development of peripheral neuropathy has been attributed to the HIV nucleoside reverse transcriptase inhibitors.

Although the specific pathophysiology is not well understood, Moyle and Sadler [8] indicate that several nucleoside antiretroviral agents such as zalcitabine, stavudine, and didanosine cause peripheral neuropathy within 3 months and other related comorbidities such as cardiorespiratory-related illnesses, neuro-musculo-skeletal symptoms, and pain. The finding is that long-term exposure to these inhibitors may possibly cause mitochondrial injury to the host cells, which results in mitochondrial toxicities that could lead to myopathies, enthesopathies, and pain [9]. The effects of these conditions may lead to the affected person to spend less time on vigorous activities because of the lower aerobic capacity and functional limitations; this can be attributed to a detraining effect and the resultant poor quality of life (QoL) [9–11]. It is also now being reported that in South Africa, an additional burden associated with HIV is the rate of co-infection with TB [12]. It was found that although HAART resulted in an 80% reduction in the incidence, morbidity, and mortality rates of HIV-associated TB, there is evidence that co-infected patients become more ill following the commencement of antiretroviral therapy, and the condition is referred to as paradoxical worsening of TB symptoms [13]. This could be attributed to the interaction of TB and HIV medications, as there is reconstitution of the immune response to mycobacteria caused by rifampicin, an anti-TB drug that metabolizes protease inhibitors and non-nucleoside reverse transcriptase inhibitors [14]. Since the incidence and prevalence rates of HIV/AIDS are still on the increase, the South African health services are challenged by the double impact of an increase in HIV-related illnesses and TB; financial and human resources available to meet these challenges, mainly in public hospitals, are limited. An additional factor is that individuals on HAART follow a strict medication regime and possibly have to take additional medications for TB, pain, psychological disorders, and other pathologies related to HIV, which may result in these individuals becoming overwhelmed by the number of medications and protocols. The side effects of antiretrovirals may also be contributing to the compromise of the value of medical management and the relatively poor QoL of these individuals. Therefore, alternative therapies are warranted and necessary so that the affected individuals have options in terms of potential treatment outcomes. This will help maintain or improve their QoL and motivate them to adhere to and comply with HAART, thus maintaining CD4 cell counts of greater than 200 cells/mm³, critical for therapeutic success in the treatment of HIV infection. This will also result in improvement in scores for most domains of QoL, assessed using health-related questionnaires [15].

1.2 Quality of Life

With the introduction of HAART, an improvement has been seen in the QoL of the affected individuals, although the outcomes may be different, depending on the person’s baseline QoL [16]. Over a period with the use of HAART, it has been found that there are side effects or adverse effects associated with the use of these medications. The resulting physical, psychological, metabolic, or morphologic manifestations are associated with anthropometric abnormalities caused by body fat redistribution [17]. Symptoms such as pain, nausea, fatigue, anxiety, depression, or impaired psychosocial deficits result in the affected individuals either discontinuing or not complying with their course of medication or turning to complementary and alternative forms of therapies. These may include, but are not limited to, acupuncture, massage, homeopathy, and vitamin supplements. The main objective of these alternative therapies is to improve the health and subjective perceptions of the individual. These perceptions may include assessment of life in terms of happiness, life satisfaction, and positive effects that may reflect not only how they feel physically but, to some extent, what their health allows them to do functionally as well. The reason for this is that good health, which can be regarded as absence of mental, physical, and psychological symptoms and the ability to achieve and maintain maximal functional independence and autonomy, is an important factor that contributes to a good QoL. Therefore, rehabilitation techniques focus on maintaining, restoring, and enhancing the QoL in individuals with HIV and is an important outcome for HIV treatment [18–20]. Physical movement is the cornerstone for performing recreational activities or activities of daily living (ADLs) and also improves psychosocial and mental health. Limitations in mobility of individuals with HIV who may or may not be receiving HAART were shown to be commonly associated with problems such as pain and loss of muscle power and neuro-musculo-skeletal and related functions because patients often avoid physical activity as they fear that this will cause injury and worsen the pain. These symptoms and physical impairments can influence coping strategies and have a negative effect on the QoL and health of the infected individuals [21,22]. Rehabilitation programs must therefore consider mobility and QoL as important goals when initiating any form of therapy for individuals affected by HIV/AIDS. It is often found that questionnaire-based methods are commonly used to assess the health status of people with HIV/AIDS. These measures are often used to determine the effects of medical, physical, and community-based health interventions. One of the generic questionnaires used to assess the measures of QoL is the Short Form-36 Medical Outcomes Study (SF-36). This questionnaire measures the outcome of health care delivery and is also used to monitor people living with HIV/AIDS in South Africa, as patient-reported measures of QoL are likely to be reliable and valid methods of assessing the impact of different HIV/AIDS interventions within the African context. [23,24]. Following the use of this instrument, patients can be assessed with the primary aim of rehabilitation to restore the patient to optimal physiologic and psychological health, relieving pain, encouraging movement, and potentially relieving stress and depression. The paradigm shift of any rehabilitation intervention must therefore be related to the goal of improving short-term function by decreasing discomfort and increasing mobility to an emphasis on long-term independent function, placing the emphasis on patient-based outcomes and improvement in QoL as the main objectives of treatment [25,26]. QoL, therefore, becomes important factor in determining the impact of chronic diseases on patients’ lives, and improvement in QoL should be recognized as an significant outcome in the treatment of HIV [19,25,27].

1.3 Exercise and HAART

Generally, exercises are known to improve immune function and QoL of the individuals with HIV by improving their lung function, breathing, and ventilation and their physical and emotional status and by delaying AIDS-related complications [28]. However, it appears that medications used in HAART, mainly zidovudine and didanosine, have variable effects on exercise tolerance, physical and psychological challenges, and motivation due to decrease in the performance of activities. Various studies have indicated that vigorous activity and aerobic capacity are lower among those on HAART as the infected individuals reported climbing fewer stairs and walking fewer blocks per day, and fewer of them were employed because they did not have the physical capacity to work [29–32]. Even in the absence of clinical immunosuppression, infected individuals experience depression, disabilities, activity limitations, and restricted participation due to pain and diminished muscle power and movement-related functions; thus, they avoid physical activity fearing that this will worsen the pain and cause further injury [21]. Physiologically, persons of all ages infected with HIV show low functional capacity, which is expressed as lowered capacity to utilize oxygen and perform work [33]. The ability to utilize oxygen is referred to as functional aerobic capacity, and studies have shown that individuals with HIV have a maximal functional aerobic capacity of 24–44% below the normal values for their age [29]. It is generally acknowledged that physical activity provides health benefits, with moderate physical activity being one of the primary interventions in the treatment of some diseases [32,34]. In the pre-HAART era, physical activity three or more times per week was associated with slower progression to AIDS, and an inverse relationship was seen between viral load and physical activity [28,35,36]. In the era of HAART, studies have shown that physical activity is recommended for the treatment and prevention of cardiovascular disease, lipodystrophy, and insulin resistance and to improve the health-related QoL in individuals with HIV [37–39]. Since the introduction of HAART, although the lifespan of the infected individuals has been prolonged, specific adverse effects, including neuropathy, fatigue, insomnia, nausea, diarrhea, vomiting, skin rashes, anemia, body fat distribution, and psychiatric symptoms, occur following long-term use of HAART medications, [40]. Since rehabilitation management and techniques require self-activity to ensure physical and mental health, one of the primary methods to facilitate this is through the engagement of these individuals to participate in exercise programs. The premise is that an improvement in the participants’ feeling of physical and mental well-being will likely serve as positive reinforcement, which may provide an impetus for engaging in and continuing with the exercise programs.

1.3.1 Exercise Activities

Many studies have indicated the benefits of aerobic, resistance, or combination exercises to patients infected with HIV and receiving HAART [28,41,42]. Exercise has been associated with an improvement in self-confidence, sense of well-being, and mental relaxation, all of which have a positive impact on the overall QoL [43]. Aerobic exercises incorporating treadmill activities, cycle ergometer, jogging, walking, running, and other exercises related to cardiorespiratory fitness have been advocated as being beneficial for persons with HIV and those receiving HAART. Some of these studies have focused on the general benefits of exercises to physical function and others specifically on the QoL of individuals with HIV. In a study using a rehabilitation program of moderate-intensity cycling and treadmill exercises, incorporating a home exercise program for patients on HAART, the findings were that there was a significant improvement in the QoL in those individuals participating in the study with no adverse effects from these exercises [44]. This study also found that sick days from work decreased from a mean of 7 days to 3 days. The female dropout rate was significant, as more females dropped out of the study compared with men. In a study not based on exercise programs, Ajithkumar et al. [45] noted that the majority of patients receiving antiretrovirals went back to their jobs. Evidence has shown that women have a higher incidence of psychological symptoms and greater psychological distress [46]. Therefore, it seems that the physiological manifestation of HIV is different in women than in men [18], which could be a reason for women not participating in rehabilitation programs to the same extent as do men. However, this is in contrast to the study by Keyser et al. [33], in which female participants were found to be either less affected by their infection or their lifestyles required more time to be spent on other activities, which could be the reasons for females not seeing the benefit of participating in formal exercise or rehabilitation programs. The study by Maharaj and Chetty [44] on exercises also noted significant improvements in physical and mental component scores following the exercise program, possibly due to improvements in the participants’ feeling of physical and mental well-being serving as positive reinforcement and providing an impetus for continuing with the exercise program. It was also shown that functional limitations common in individuals with HIV due to detraining could be reversed by adherence to a moderate exercise program [47]. Although various types of exercise seem to have positive effects on the individual with HIV, rehabilitation professionals have noted that sometimes resource-poor communities and facilities do not have the necessary infrastructure for running successful exercise programs and that individuals with HIV fatigue easily or show no interest in exercise regimes. Therefore, alternative methods of exercise activities are warranted. One such exercise is the rebound exercise.

1.3.2 Rebound Exercise

Rebound exercise performed on a mini-trampoline with an elastic surface and springs, including gravity-assisted vertical movements, is a relatively new type of exercise recommended inter alia to improve cardiorespiratory fitness [48] (Figure 1.1). Rebound exercise can vary in intensity, depending on the age and fitness of the individual; feet are either in constant contact as in a bouncing movement or raised above the elastic surface, depending on jump height assisted by gravity, springs, and a handlebar for support (Figure 1.2). Bounce or jump frequencies can be monitored by signals from an electronic metronome, which, when set at a minimum of 60 per minute and height of 15 cm, does not provoke an increase in maximal oxygen consumption (VO2) or energy expenditure [49]. The benefit of this is that the signal from the metronome can act as a means of feedback to the individual, and if a successful number of bounces are performed, it can serve to motivate the patient. Thus, it encourages further activity, and the relative stability of VO2 will not lead to fatigue of the individual. It is, therefore, a suitable exercise for an individual who has either respiratory compromise such as pulmonary TB or other challenges related to activity and exercises. Anecdotal reports indicate that patients enjoy the bouncing and jumping activities and also cope adequately with rebound exercise, as patients with neuro-musculo-skeletal weakness use the handlebars for support and stability. The elastic surface of the trampoline and the springs facilitate movement. The additional benefit is the avoidance of a jarring effect on the musculoskeletal system, mainly on joints affected by arthritis and osteoporosis, which commonly prevent individuals from engaging in other aerobic exercises such as jogging and treadmill activities. Cycle ergometer exercises can be beneficial to individuals with arthritis or osteoporosis; mobilization in standing, which is possible with gentle bouncing on the trampoline, improves functional residual capacity, oxygen saturation, and the partial pressure of oxygen and reduces the partial pressure of carbon dioxide with short-term improvements in tidal volume, inspiratory flow rate, and minute volume [50]. Studies indicating the effect of exercises in individuals presenting with pathologies are limited, but some of the initial studies have indicated that rebound exercise has the potential to benefit certain conditions.

Figure 1.1 The rebounder (mini-trampoline).

Figure 1.2 Feet in contact (handlebar for safety).

1.3.3 Studies with Rebound Exercise

The author has conducted two studies with different exercise programs for individuals with HIV using rebound exercise to determine its effect as follows:

1. Cycle ergometer and rebound exercises with chest physiotherapy: a useful adjunct for sputum expectoration in mild to moderately symptomatic HIV infected children [51]. This study was conducted on children aged 8–12 years with mild to moderately symptomatic HIV, who presented with difficulty expectorating sputum. The volumes of sputum produced following cycle ergometer or rebound exercise after chest physiotherapy were compared. Both exercises were found to be safe for these children, but the combination of rebound exercise and physiotherapy resulted in the production of significantly more sputum. This combination was, therefore, considered useful to remove excess sputum commonly occurring in these children.

2. Chest physiotherapy and rebound exercise for sputum in patients co-infected with TB and HIV [52]. This study focused on the use of rebound exercise as a potential adjuvant with chest physiotherapy for sputum induction in patients who were co-infected with TB and HIV and were on HAART. A significant amount of sputum was produced when rebound exercise was followed by chest physiotherapy compared with a group receiving only chest physiotherapy. The acid-fast bacilli yield also improved after the combination of rebound exercise and chest physiotherapy. The additional benefit was less exposure to infected patients and thus a reduction in nosocomial TB infections and minimization of direct interaction with patients with HIV and TB co-infection. This is a significant advantage in the South African health care environment, as the health care professionals are already challenged by the HIV pandemic and the increasing incidence of TB. Co-infection has placed an enormous financial and human resource burden on the South African public health care. However, as the combination of rebound exercise with chest physiotherapy is a cough-generating and respiratory-facilitated procedure, biosafety measures must be implemented strictly, and rebound exercise should be used with caution due to the risk of increase in respiratory and blood pressure rates.

1.3.4 Precautions During Rebound Exercise

In both studies listed above, as the patients have cardiorespiratory compromise, an increase of 30% from baseline (preintervention) values of systolic or diastolic blood pressure during the exercise was deemed an indication that the patient was reaching an unstable state and the exercise was to be stopped [53]. Moderate intensity of exercise was between 50% to 60% of the age-predicted maximum heart rate (220-age in years), and a rate of 10 beats within this percentage was set as the predicted maximum for safety [54]. In general, as respiratory and blood pressure rates increased during rebound exercise these vital characteristics should be closely monitored during the use of this exercise in HIV-infected and other respiratory compromised patients.

1.3.5 Physiologic Responses Following Rebound Exercise

The significant amount of sputum produced with rebound exercise may be associated with the exercise facilitating strength and function of the respiratory system, which influences pulmonary pressures, volume, breathing depth, and frequency [55]. Physiologically, inspiratory muscles, including the diaphragm, are morphologically and functionally skeletal muscle, and patients with compromised elasticity of lung tissue will experience hyperinflation with shortening and flatting of the diaphragm resulting in altered length and decreased force production [56]. Rebound exercise, which requires rhythmic bouncing on the elastic surface and is assisted by gravity and springs, enhances the movement of the diaphragm and lung tissue into repetitive wavelike movements. This facilitates breathing excursions and mucus clearance by hyperventilation, which leads to high air flow and mechanical squeezing. The increase in mucus clearance is achieved by the mimicking of the active cycle of breathing techniques and natural work of breathing, which clears a significant volume of secretions from the bronchial tree and improves bronchopulmonary secretion and lung function [57,58]. Similar to the findings in the study by Weston et al. [59], other studies have also shown that the respiratory rates increased significantly in the rebound exercise group, as some patients may have bounced more than the prescribed minimum of 60 per minute. This may have caused an increase in step frequency and thus an increase in the respiratory rate but with no significant increases in the heart rate. These findings support the use of rebound exercise, as during treadmill exercises, an increase in heart rates has a linear increase in VO2 [59], which may be reduced in respiratory-compromised patients with HIV and TB co-infection. The hypertensive readings post-rebound exercise could be related to positive and negative lower body position changes, which alter central and thoracic blood volumes, causing changes in central venous pressure and mean values of systolic blood pressure. Systolic blood pressure also increases with exercise duration, peaking at 12 min at a heart rate of 160 beats per minute (beats/min), and diastolic pressure remains fairly constant, which must be noted during the use of rebound exercise [60,61].

1.3.6 Rebound Exercise and QoL

In an unpublished longitudinal study over 9 months, 69 patients on HAART for a minimum period of 3 years or more were recruited and subjected to rebound exercise. One of the aims of the study was to determine the effect of rebound exercise on the QoL domains of physical and mental components. Thirty minutes of rebound exercise twice per week improved the physical and mental components from baseline, peaking in the third month and marginally declining in months 6–9 (Figure 1.3). This may be due to rebound exercise having maximal physiologic and mental benefits during this period for the participants. However, over a longer period, the benefits decrease, which may possibly be due to physiologic adaptations of the body to the effects of the exercise and the decreased motivation of the individual, which lowered the values of the mental component.

Figure 1.3 Physical and mental component scores following rebound exercise (n = 69).

1.4 Summary and Clinical Implications

The era of HAART has seen significant changes in comorbidities associated with HIV in infected individuals. Peripheral neuropathy, TB, cerebral vascular accidents, musculoskeletal pain, and enthesopathies are commonly associated with the use of HAART and require medical and rehabilitation management. The overall aim of medication is to prevent and manage comorbidities associated with the virus, and rehabilitation programs aim to restore, maintain, and enhance the QoL and avoid inactivity in individuals with HIV due to the detraining effect. There are various ways to encourage activity and improve the QoL in this population with the use of exercise programs. The management of the virus and the comorbidities associated with it and the psychosocial aspects present challenges to health care professionals. Rehabilitation professionals must therefore contribute to the overall management by encouraging activities that are safe, manageable, and enjoyable for this population. Exercises, in particular rebound exercise, seem to have beneficial outcomes in these individuals and should therefore be encouraged. However, any exercise program must be used with appropriate caution in this population.

References

1. O’Brien K, Nixon S, Tynan A, Glazier R. Effectiveness of aerobic exercise on adults living with HIV/AIDS: systematic review. Med Sci Sports Exerc. 2004;36(10):1659–1666.

2. Scevola D, Di’Matteo A, Lanzarini P, Uberti F. The effect of exercise and strength training on cardiovascular status in HIV-infected patients receiving highly active antiretroviral therapy. AIDS. 2003;17:123–129.

3. Centre for Disease Control and Prevention. HIV/AIDS surveillance report. 2003;15:1–46.

4. Gange SJ, Barron Y, Greenblatt RM, Anatos K. Effectiveness of highly active antiretroviral therapy among HIV-1 infected women. J Epidemiol Community Health. 2002;56:153–159.

5. Rusch M, Nixon S, Schilder A, et al. Impairments, activity limitations and participation restrictions: prevalence and associations among persons living with HIV/AIDS in British Columbia. Health Qual Life Outcomes. 2004;6(2):46.

6. Dorrington R, Bradshaw D, Johnson L, Budlender D. The demographic impact of HIV/AIDS in South Africa: national; indicators for 2004 Cape Town: Centre for Actuarial Research and South African Medical Research Council; 2004.

7. Parry O, Mielke J, Latif AS, et al. Peripheral neuropathy in individuals with HIV infections in Zimbabwe. Acta Neuro Scand. 1997;96:218–222.

8. Moyle GJ, Sadler M. Peripheral neuropathy with nucleoside antiretroviral therapy: risk factors, incidence and management. Drug Saf. 1998;19:481–494.

9. Gerschenson M, Brinkman K. Mitochondrial dysfunction in AIDS and its treatment. Mitochondrion. 2004;4:763–777.

10. Simpson DM, Tagliati M. Neurological manifestations of HIV infection. Ann Intern Med. 2004;121:769–785.

11. Carr A, Emery S, Law M, Puls R, Lundgren JD, Powderly WG. An objective case definition of lipodystrophy in HIV-infected adults: a case controlled study. Lancet. 2003;361:726–735.

12. Naidoo S, Jinabhai CC. TB in health care workers in KwaZulu-Natal, South Africa. Int J Tuberc Lung Dis. 2006;10:676–682.

13. Narita M, Ashkin D, Hollender ES, Pitchenik AE. Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS. Am J Respir Crit Care Med. 1998;158:157–161.

14. McShane H. Co-infection with HIV and TB: double trouble. Int J STD AIDS. 2005;16:95–101.

15. Abera K, Gedif T, Engidawork E, Gebre-Mariam T. Quality of life of people living with HIV/AIDS and on highly active antiretroviral therapy in Ethopia. Afr J AIDS Res 2010;(Suppl. 1):31–40.

16. Nieuwkerk PT, Hillebrand ME, Vriesendorp R, et al. Effect on patient’s quality of life of starting HAART at different CD4 cell counts. Poster presentation at the 14th international AIDS conference, Barcelona, Spain; 7–12 July 2002.

17. Hicks C, Currier J, Sax P. Current management challenges in HIV: tolerability of antiretrovirals and metabolic complications. AIDS Patient Care STDS. 2003;17:221–233.

18. Solomon P, Wilkins S. Participation among women living with HIV: a rehabilitation perspective. AIDS Care. 2008;20(3):292–296.

19. Wu AW. Quality of life assessment comes of age in the era of highly active antiretroviral therapy. AIDS. 2000;14:1449–1451.

20. Franchi D, Wenzel RP. Measuring health-related quality of life among patients infected with human immunodeficiency virus. Clin Infect Dis. 1998;26:20–26.

21. Van As M, Myezwa H, Stewart A, Maleka D, Musenge E. The International Classification of Function Disability and Health (ICF) in adults visiting the HIV outpatient clinic at a regional hospital in Johannesburg, South Africa. AIDS Care. 2009;21(1):50–58.

22. Cunningham WE, Crystal S, Bozette S, Hays R. The association of health-related quality of life with survival among persons with HIV infection in the United States. J Gen Inter Med. 2005;20:21–27.

23. O’Keefe EA, Wood R. The impact of human immunodeficiency virus infection on quality of life in a multiracial South African population. Qual Life Res. 1996;5:275–280.

24. Mast TC, Kigozi G, Wabwire-Mangen F, et al. Measuring quality of life among HIV-infected women using a culturally adapted method in Rakai district Uganda. AIDS Care. 2004;16:81–94.

25. Cohen C. On the quality of life: some philosophical reflections. Circulation. 1982;66(Suppl. 111):29–33.

26. Call SA, Klapow JC, Stewart KE, et al. Health-related quality of life and virologic outcomes in an HIV clinic. Qual Life Res. 2000;9:977–985.

27. Guyatt GH, Feeney DH, Patrick DL. Measuring health-related quality of life. Ann Intern Med. 1993;118:622–629.

28. Stringer WW. HIV and aerobic exercise. Sports Med. 1999;28(6):389–395.

29. MacArthur RD, Levine SD, Birk TJ. Supervised exercise training improves cardiopulmonary fitness in HIV-infected persons. Med Sci Sports Exerc. 1993;25(Suppl. 6):684–688.

30. Cade WT, Fantry LE, Nabar SR, et al. A comparison of Qt and a-vO2 in individuals with HIV taking and not taking HAART. Med Sci Sports Exerc. 2003;35:1108–1117.

31. Cade WT, Peralta L, Keyser RE. Aerobic exercise dysfunction in human immunodeficiency virus: a potential link to physical disability. Phys Ther. 2004;84:655–664.

32. Smit E, Crespo CJ, Semba RD, et al. Physical activity in a cohort of HIV-positive and HIV-negative injection drug users. AIDS Care. 2006;8(8):1040–1045.

33. Keyser RE, Peralta L, Cade WT, Miller S, Anixt J. Functional aerobic impairment in adolescents seropositive for HIV: a quasi-experimental analysis. Arch Phys Med Rehabil. 2000;81(11):1479–1484.

34. US Department of Health and Human Services. Physical activity and health: a report of the surgeon general Atlanta, GA: Centre for Disease Control and Prevention; 1996.

35. Mustafa T, Sy FS, Macera CA, Thompson SJ, Jackson KL, Selassie A. Association between exercise and HIV disease progression in a cohort of homosexual men. Ann Epidemiol. 1999;9:127–131.

36. Bopp CM, Phillips KD, Fulk LJ, Hand GA. Clinical implications of therapeutic exercise HIV/AIDS. J Assoc Nurses AIDS Care. 2003;14(1):73–78.

37. Aberg JA. Cardiovascular risk among HIV-positive patients on antiretroviral therapy. J Int Assoc Physicians AIDS Care 2003;(Suppl. 2):S24–S39.

38. Bergersen BM, Sandvik L, Bruun JN, Tonstad S. Elevated Framingham risk score in HIV-positive patients on highly active antiretroviral therapy: results from a Norwegian study of 721 subjects. Eur J Clin Microbiol Infect Dis. 2004;23:625–630.

39. Clingerman E. Physical activity, social support and health-related quality of life among persons with HIV disease. J Community Health Nurs. 2004;21:179–197.

40. Doerfler RE. Sweetening the toxic cocktail: managing the side effects of HIV medications. Adv Nurse Pract. 2002;10:52–103.

41. Dolan SE, Frontera W, Librizzi J, et al. Effects of a supervised home-based aerobic and progressive resistance training regimen in women infected with human immunodeficiency virus: a randomized trial. Arch Intern Med. 2006;166(11):1225–1231.

42. Filipas S, Oldmeadow LB, Bailey MJ, Cherry CL. A six month supervised aerobic and resistance exercise program improves self-efficacy in people with human immunodeficiency virus: a randomized controlled trial. Aust J Physiotheraphy. 2006;52(3):185–190.

43. O’Neil K, Reid G. Perceived barriers to physical activity by older adults. Can J Public Health. 1991;82:392–396.

44. Maharaj SS, Chetty V. Rehabilitation program for the quality of life for individuals on highly active antiretroviral therapy in KwaZulu-Natal, South Africa: a short report. Int J Rehabil Res. 2011;34:360–365.

45. Ajithkumar K, Iype T, Arun KJ, Ajith BK, Aveenlal KPR, Anthony TP. Impact of antiretroviral therapy on vocational rehabilitation. AIDS Care. 2007;19(Suppl. 10):1310–1312.

46. Derogatis LR, Derogatis MF. Quality of life and pharmaco-economics in clinical trials 2nd ed Philadelphia, PA: Lippincott-Raven; 1996.

47. Hand GA, Phillips KD, Dudgeon WD, Lyerly WG, Durstine JL, Burgess ES. Moderate intensity exercise training reverses functional aerobic impairment in HIV-infected individuals. AIDS Care. 2008;20(9):1066–1074.

48. Carter AE. The new miracles of rebound exercise New York, NY: Rebound Air Inc: Nature Distributors; 1988; (pp. 19–51).

49. Smith JF, Bishop PA. Rebounding exercise: are the training effects sufficient for cardio-respiratory fitness? Sports Med. 1998;5:6–10.

50. Zafiropoulos B, Alisson JA, Mc Carren B. Physiological responses to the early mobilization of the intubated ventilated abdominal surgery patient. Aust J Physiother. 2004;50(2):95–100.

51. Maharaj SS, Jeena PM. Cycle ergometer and rebound exercises with chest physiotherapy—a useful adjunct for sputum expectoration in mild to moderately symptomatic HIV-infected children. S Afr J Physiotheraphy. 2008;64(3):37–42.

52. Maharaj SS, Dunpath T. Chest physiotherapy and rebound exercise for sputum in patients co-infected with TB and HIV. S Afr J Physiotheraphy. 2014;70(3):10–14.

53. Lim PO, MacFayden RJ, Clarkson PB, MacDonald TM. Impaired exercise tolerance in hypertensive patients. Ann Intern Med. 1996;124:41–55.

54. American College of Sports Medicine. Guidelines for exercise testing and prescription 6th ed. Philadelphia, PA: Williams & Wilkins; 2000.

55. Clanton TL, Dias PT. Clinical assessment of the respiratory muscles. Phys Ther. 1989;75:983–995.

56. Enrich SJ, Unnithan VB, Heward C, Withnall L, Davies DH. Effect of high-intensity inspiratory muscle training on lung volumes, diaphragm thickness and exercise capacity in subjects who are healthy. Phys Ther. 2006;86(3):345–354.

57. Márquez G, Aguado X, Alegre LM, Lago A, Acero RM. The trampoline after effect: the motor and sensory modulation associated with jumping on an elastic surface. Exp Brain Res. 2010;204:575–584.

58. Pryor JA, Webber BA. Physiotherapy for respiratory and cardiac problems London: Churchill Livingstone; 1999; pp. 140–47.

59. Weston AR, Khan A, Mars M. Does heart rate adequately reflect exercise intensity during mini-trampoline exercise? S Afr J Sports Med 2001;99–113.

60. Coast RJ, Kroy JA, Akers FM, Dahl T. Effects of lower body pressure changes on pulmonary function. Med Sci Sports Exerc. 1998;30(7):1035–1040.

61. Olsen R, Amlie A, Omvik P. Blood pressure monitoring. J Appl Physiol. 2002;7:149–156.

Chapter 2

Metabolic Abnormalities in HIV-Infected Populations without or with Antiretroviral Therapy (ART)

Nazisa Hejazi and Roslee Rajikan,    Dietetics Program, School of Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia

Irregularities in blood metabolic parameters have been detected in the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) era prior to and during the period of treatment with HIV medications. Serum lipids and glucose concentrations, which are highly prevalent metabolic abnormalities, have been affected unfavorably in different patterns. Low concentrations of serum cholesterol and high-density lipoprotein cholesterol (HDL-c) are typically manifested during infection with HIV, whereas increased levels of serum triglycerides (TG), cholesterol, and glucose are well-known metabolic disorders seen during therapy for advanced HIV. In general, serum lipids and glucose disorders are more common and severe with some HIV medicines, which play significant roles in these metabolic complications. Based on the availability of various HIV medicines, the mechanism and pathway, occurrence rate, and severity may be dissimilar for each class of HIV medicine. This chapter introduces and explicates the findings of studies on HIV-associated metabolic abnormalities without and with antiretroviral therapy (ART) in detail.

Keywords

Metabolic abnormalities; HIV; antiretroviral therapy; highly active antiretroviral therapy; nucleoside reverse-transcriptase inhibitors; non-nucleoside reverse-transcriptase inhibitors; protease inhibitors; dyslipidemia; glucose intolerance; diabetes

2.1 Introduction

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), a set of clinical signs and symptoms, is not similar to other infectious diseases. It cannot be seen merely in the form of ordinary clinical manifestations of infection, such as fever, appetite loss, fatigue, or pain. In fact, this unique infectious syndrome can negatively affect all vital human body organs through deleterious changes in the form of weakening the immune system. As the results of spectrum immune alterations, some metabolic abnormalities can be seen early in the course of HIV infection. Aggravations in lipid and glucose metabolism and insulin resistance (IR) are examples of highly prevalent metabolic dysregulations [1–10]. HIV can interact with metabolic irregularities in many pathways. Another aspect of metabolic abnormalities can be explained in relation to HIV treatment, which has altered the clinical picture of this infection by declines in morbidity and mortality rates. These metabolic disorders are caused mainly by the introduction of some HIV medicines [1,8,10]. Some of these complications such as dyslipidemia, IR, and increased serum glucose can be recognized before or during HIV/AIDS treatment, particularly with the initiation of advanced and multiple antiretroviral therapy (ART), which is also referred to as highly active antiretroviral therapy (HAART). Before treatment with antiretroviral medication, rise of serum triglyceride (TG) level, decreases of high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) levels, as well low or high levels of serum glucose, were attributed to HIV infection, whereas ART regimens have dissimilar effects on lipid and glucose metabolisms among people living with HIV/AIDS (PLHIV) [11–14]. During prescriptions of antiretroviral agents, high serum concentrations of TG, TC, LDL-c, and plasma glucose and low level of HDL-c are associated with treatment. It is believed that the most of the hallmark influences of anti-HIV drugs in terms of metabolic complications are caused by a third class of antiretroviral agent, called the protease inhibitor (PI) [1,8,9,11]. Moreover, other associated risk factors increase the possibility of the occurrence of these disorders. Overall, these metabolic instabilities might be caused by a cluster of influences, comprising the adverse effects of anti-HIV drugs, the nature of HIV, environmental or lifestyle factors, and individual genetic susceptibility. Remarkably, cardiovascular diseases (CVDs) are the one of tragic consequences of these multiple metabolic illnesses, also called noncommunicable diseases (NCDs). Increasing in ART receiving rates (with a global target of 15 million people living with HIV [PLHIV]) from 54% at the end of 2011 to 65% in 2012, as reported by the World Health Organization (WHO) in 2013 [2], may elevate the incidences of these NCDs in the future. Understanding of the extremely complicated and multifactorial pathogeneses of these metabolic alterations is worthwhile for implementation of preventive programs and therapeutic management. This chapter explains the definition and type of metabolic abnormalities, epidemiology, pathophysiology (mechanism), and associated risk factors, as well studies and findings in relation to these topics. On account of the importance of HIV infection and the role of ART in the occurrence of these abnormalities, two sections in this chapter provide information on the courses of metabolic associated disorders without ART and with ART.

2.1.1 Metabolic Abnormalities

Metabolic abnormalities have been defined as a part of lipodystrophy syndrome in patients with HIV. HIV-associated lipodystrophy syndrome, which was first defined in 1998 [1], is characterized by undesirable metabolic and morphologic changes, including dyslipidemia, IR, and body fat redistribution. Dyslipidemia, which is a range of increased levels of serum TG (hypertriglyceridemia), LDL-c, and TC (hypercholesterolemia) and also low concentration of HDL-c, may or may not be associated with serum glucose disturbances. Also, IR and serum glucose disorders are frequently seen with this infection. In IR, body cells are unable to respond to the normal biologic activities of the hormone insulin so that the excess levels of insulin circulating in blood (hyperinsulinemia) almost reveals the IR [4]. Lack of insulin production as a result of defects in β-cells, which make insulin hormone in the pancreas and release it into the bloodstream, IR, or both are the other causes of glucose abnormalities in blood and human tissues. IR and serum glucose irregularities lead to numerous morbid illnesses, including impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), hypertension, coronary heart diseases (CHDs), and CVDs [3,4]. However HIV-associated body fat disorders are typically caused by the adverse effects of HAART, which alters body composition, and are considered morphologic changes. Excess local body fat accumulations (lipohypertrophy) in the abdomen as visceral fat, back of neck (buffalo hump), breast, liver, epicardium, and muscles may be seen with loss of subcutaneous adipose tissue (lipoatrophy). Lipoatrophy is observed in the extremities, including the arms and legs; in the face as shrunk temporal and periorbital fat pad; and in the chin as nasolabial double fold [5,6], which are the well-known morphologic alterations [1,7]. In most cases, body habitus changes are linked to blood lipid abnormalities in the form of high levels of TC, LDL-c, TG, or a combination of these [8,9].

Overlay metabolic disorders associated with HIV infection and ART can be summarized as follows:

 Dyslipidemia

 Hypertriglyceridemia

 Hypercholesterolemia

 Low HDL levels

 Abnormal glucose metabolism

 IR

 IGT

 Diabetes mellitus

2.1.2 Grading of Severity in Dyslipidemia and Abnormal Glucose Level

Definitions and classifications for serum lipids and glucose are slightly different in the HIV/AIDS era. The descriptions and categorizations recommended by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) with regard to blood metabolic abnormalities, which are presented in Table 2.1, are widely used by researchers and clinicians in HIV studies [10].

Table 2.1

National Cholesterol Education Program Adult Treatment Panel III Approach to Dyslipidemia and Hyperglycemia

2.1.3 Anti-HIV Drugs by Class

The recent six classes of antiretroviral drugs (Table 2.2) comprise nucleoside reverse-transcriptase inhibitors (NRTIs), non-nucleoside reverse-transcriptase inhibitors (NNRTIs), PIs, fusion inhibitor (FI), and integrase inhibitor, which is also referred to as integrase strand transfer inhibitors (INSTIs). As a result of failure in first-line treatment with NRTIs, NNRTIs, or both, clinicians switch from first-line ART to second-line ART, which consists of two NRTIs+one PI [11] in both adults and children. Third-line regimens include new drugs such as integrase inhibitors, FIs, CCR5 antagonists, or new agents of second-generation NNRTIs and PIs. Switching to another line may be due to failure with previous line regimens, ART intolerance, or severe side effects of antiretroviral agents.

Table 2.2

The Clustering of Anti-HIV Medications by Class

Source: Adapted from guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents [11].

2.2 HIV-Associated Metabolic Abnormalities without ART

Irregularities in the metabolic system of patients with different HIV-1 subtypes before treatment with HIV medicine have been discussed extensively [12]. In the 1980s and 1990s, hormonal and metabolic derangements were observed in ART-naïve patients with HIV. One of the obvious examples of these alterations is lipid disorder, which has been observed in the form of decreased HDL-c, increased serum TG, and decreased cholesterol levels as the result of decreased clearance of very-low-density lipoprotein (VLDL-c) during advanced stages of AIDS [12–14]. This information about alterations in lipids was mainly obtained from cases of wasting syndrome in AIDS. Unfortunately, there are few studies on HIV-related metabolic disorders among the ART-inexperienced individuals with HIV from early in the HIV epidemic, although much attention was given to the severity and high incidence rates of the metabolic side effects of the antiretroviral classes.

2.2.1 Pathophysiology of Serum Lipid Disorders

Given the complexity of HIV/AIDS, many factors, including inflammatory conditions, endocrine disorders, and so on, contribute to HIV-related metabolic disorders. There are some theoretic concerns regarding the pathogeneses of lipid disorders induced by HIV. Blood lipid deregulations are common because of host responses to infections with bacteria, fungi, viruses, or other infective microorganisms. The host cells in mammals encounter significant metabolic alterations through the secretion of inflammatory markers, which exert protective actions against pathogens.

Cytokines are wide-ranging inflammatory indicators, which mainly act as the tumor necrosis factor (TNF) in reaction to bacterial contaminations, and interferons (IFNs) act as key cytokines in response to viral diseases [15–17]. Generally, cytokine activities lead to elevation of lipid peroxidation and the production of reactive oxygen species and free radicals, which damage the molecular structures of lipids [18]. As another mechanism, TNF, IFN-α, IFN-ϒ, interleukin 1 (IL-I), and IL-6, which are the main cytokines, have catabolic effects on fat cells through a decline in lipoprotein lipase activity and an upsurge of lipolysis (breakdown of lipids) in fat tissues [19–21]. The first atypical manifestation of a blood lipid is a rapid increase in serum TG level [22–24]. Overall, hepatic synthesis of fatty acids and VLDL-c by these cytokines [22,25] lead to the production of TG in the liver.

A good example of the effect of inflammatory markers on blood lipid profile can be seen in relation to the low HDL-c level [26]. Low serum concentration of HDL-c has been diagnosed in individuals with HIV who are not receiving ART [27], which was unrelated to the CD4+T-lymphocyte count [28,29]. Similarly, high-level productions of inflammatory cytokines such as TNF, IL, and IFN cause an upsurge in serum TG levels with progression in HIV infection and opportunistic infections, which possibly raise the serum amounts of these inflammatory markers [30,31] and steroid hormones [12,28]. Consequently, an increase in cytokines such as IFN-α causes elevations in serum concentrations of TC, TG, VLDL-c, apolipoprotein B (apoB: primary component of chylomicrons, VLDL-c and LDL-c), and apoB/apoA1 (apolipoprotein A1: the major protein component of HDL-c in plasma) [32]. These lipid alterations could be partially explained by the fact that the production of inflammatory factors and a weakened immune system can alter lipid levels unfavorably. This also explains why health care professionals consider a low CD4 cell count the major risk component for metabolic abnormalities [33,34]. Finally, the common consensus is that the low CD4 cell count, which is an indicator of chronic inflammatory markers, is accompanied by an increased amount of TG and lower levels of TC and LDL-c. HIV can affect the endocrine system by involving glands such as the pituitary, thyroid, adrenal, and gonadal glands and the pancreas, which causes imbalances in hormonal levels [35–40]. Endocrine dysfunctions are reported to be the results of different pathways. It is assumed that HIV itself or the related illnesses can damage the endocrine glands directly, resulting in endocrine system dysfunctions. Thyroid disorders, which cause fluctuations in the levels of thyroid hormones, also have been observed in the early and progressive stages of HIV infection [35]. Before progression of HIV infection, increases in the levels of serum thyroxine-binding globulin, serum total thyroxine (T4), and triiodothyronine (T3) concentrations are possible, whereas serum T4 and T3 concentrations may decline during the stage of acute illness due to the cytokine secretions [39]. Decrease in thyroid hormones (hypothyroidism with low level of T3 and T4) caused by HIV infection may reduce the HDL-c level and elevate the TG level [40]. Hepatitis C associated with HIV may decrease the rates of hyperlipidemia [41,42] due to liver malfunction caused by hepatitis C virus (HCV) [43] and also due to the binding of HCV to the LDL receptor; HCV increases lipid uptake from blood and lowers the levels of serum lipids [44,45]. Generally, the main causes of dyslipidemia in this infection can be summarized as cytokine profile alterations, declines in lipid clearances, and upsurge of hepatic synthesis of VLDL-c