Lifestyle and other factors

Poverty and homelessness are associated with worse survival, probably reflecting co-factors such as nutrition and access to medical care. The possible effects of lifestyle factors such as anxiety and depression are being studied but no firm conclusions have yet been reached.

A study at the Chelsea and Westminster Hospital in London enrolled 168 people with HIV who had been infected for many years. The results found no associations between particular lifestyle factors including history of sexually transmitted diseases, use of recreational drugs, alcohol and tobacco, nutritional intake and use of vitamin supplements, sleep patterns, level of physical activity, use of conventional and complementary therapies and social activities and the rate of HIV disease progression. This suggests that lifestyle plays at most a minor role in influencing the course of infection.¹ Similarly, a longitudinal study involving only HIV-positive women found that lifestyle factors did not affect risk of progression over seven years.²

A recent study of nearly 600 people with HIV indicated that those who had roughly three drinks per day, with occasional bingeing, had lower CD4 cell counts than those who did not drink or who were moderate drinkers. After controlling for age, race, HIV risk behaviour, homelessness, depression, adherence, and duration in the study, heavy drinkers not taking antiretroviral therapy had CD4 cell counts that were approximately 50 cells/mm³ lower than those of untreated HIV-positive people who did not drink. Moderate drinkers did not show any significant difference from abstinent people. Viral load was not significantly affected by alcohol consumption.³

The findings imply that persons with HIV whose level of alcohol consumption may appear modest by the standards of some countries or communities, may already be closer to the threshold for starting treatment by the time they are diagnosed with HIV, and that if alcohol consumption increases after diagnosis and stays high, it will moderately affect disease progression.⁴

A smaller study of 231 HIV-positive drug users found that those who were not on antiretroviral therapy were nearly eight times more likely to experience a CD4 cell count drop below 200 cells/mm³ (from a median baseline of 310 cells/mm³) if they had two or more drinks per day.⁵

Alcohol may accelerate disease progression by stimulating expression of the CCR5 co-receptor and thus boosting HIV infection of cells.⁶  

Malabsorption , diarrhoea, and limited intake of calories, particularly protein, contribute to worsening immune function. Deficiencies in vitamin A, E, and B₁₂ and in the minerals zinc and selenium are associated with more rapid decline of CD4 cell counts.⁷

Multivitamin supplementation can slow time to disease progression and increase survival, according to a number of studies. Specifically vitamins B₁, B₂, B₃, B₆, B₉, C and E and other broad micronutrient supplements can reduce viral load, HIV-related symptoms, and progression to AIDS or death.^{8 9}

In developing countries, children born to women who took multivitamins is separately associated with decreased risk of death, increased attainment of weight by 24 months, and increased CD4 cell counts.

Researchers at Harvard studied the effect of a high-fat diet in eight simian immunodeficieny virus (SIV)-infected macaques as compared to 52 SIV-infected macaques fed a normal diet. The macaques on a high-fat diet were over five times as likely to die; had higher peak viral load and an absence of viral load rebound after acute viraemia; and higher interleukin-18 (IL-18) levels. Higher IL-18 levels were independently associated with increased viral load and mortality. Adipose tissue is known to contain cells and chemicals involved in the immune response; increased dietary fat could lead to alterations in the way HIV interacts with the body’s immune system. Fat and cholesterol are also thought to directly alter viral replication.¹⁰

Even in severely malnourished patients, however, robust early increases in CD4 cell count reduce the risk of death. A large prospective study in Zambia found that mortality risk was reduced for all patients whose CD4 cell count increased by at least 100 cells/mm³ after beginning antiretroviral therapy, regardless of their nutritional status.¹¹

In the past few years, a growing body of literature indicates that drug use not only increases the risk of acquiring HIV infection, but also speeds its progression.

Cocaine boosts the ability of HIV to infect immune system cells by suppressing the production of cytokines, such as MIP-1beta and enhancing CCR5 expression, the co-receptor used predominantly to infect cells throughout the course of HIV disease.¹² Weekly use of hallucinogens and cocaine were associated with increased risk of death in one study, although a causal connection was not explored.¹³

In a cohort of nearly 1700 HIV-positive women from the US Women’s Interagency HIV Study (WIHS), 29% of whom used crack cocaine, the drug’s use was an independent predictor of decreased CD4 cell count, increased viral load, occurrences of opportunistic illness, and AIDS-related mortality.¹⁴

After controlling for HAART adherence (self-reported at 95% or higher), alcohol use, age, race, income, education, illness duration, geographic area, and baseline markers, persistent crack users were three times as likely to die from AIDS-related causes over the eight-year study period than were non-users. Even occasional users, tested when using or abstinent, had greater CD4 cell loss and higher viral load than did equivalent non-users. When controlling for heroin use, smoking, depression, hepatitis C virus co-infection, and injecting drug use, crack users in this study were more likely to develop opportunistic illnesses than other women in the study.

The Multicenter AIDS Cohort Study (MACS, over 4000 participants) found that, after adjusting for covariates, the increased relative risk of seroconversion was 1.46 for those individuals using methamphetamines (meth). The relative risk of seroconversion for those who used poppers (inhaled nitrates) was 2.10; combined with meth use, the joint relative hazard of seroconversion was 3.05. Seroconversion risk rises in a dose-dependent proportion with the number of unprotected receptive anal sexual partners, from 1.9 for 1 partner to 9.3 for over 5 partners. Factoring in meth use, the joint relative hazard was 2.7 for one unprotected receptive anal sexual partner and the seroconversion risk rose in proportion to the number of partners.¹⁵

Using this same cohort and analysing individual clinical and laboratory data collected semi-annually before 1996 (to avoid potential effects of ART), researchers found no clinically meaningful association between the use of marijuana, cocaine, poppers, or amphetamines and the numbers and percentages of circulating CD4 and CD8 T-cells in seronegative or seropositive gay men or in the rates of clinical change for those who were HIV-positive.¹⁶

A recent study reported on in California looked at whether stimulant use might promote immune activation. In 44 individuals using cocaine, crack, or methamphetamines on a weekly or monthly basis, all had elevated neopterin levels. Those who used on a weekly basis (27) also had markedly elevated viral load and reduced tryptophan levels in contrast to a control group of 88 participants who reported not using stimulants in the past three months. After controlling for self-reported ARV non-adherence, weekly stimulant use was independently associated with higher neopterin, elevated viral load, and lower tryptophan.¹⁷

Several other studies have recently documented various mechanisms for disease progression mediated by the use of methamphetamines. Methamphetamines at pharmacological concentrations have been shown to have a direct immunosuppressive effect because they cause alkalisation of acidic organelles in dendritic cells and macrophages, inhibiting their role as antigen-presenting cells and decreasing phagocytosis of antibody-coated HIV particles. Intracellular HIV replication is increased and intracellular control of the pathogens candida albicans and cryptococcus neoformans is decreased.¹⁸  

Results of an in vivo study indicate that methamphetamine causes an upregulation of CCR5 receptor activity on macrophages, enhancing HIV infection through inhibition of endogenous interferon-alpha expression.¹⁹ Another study found that HIV seropositive individuals who used methamphetamine had greater neuropathological abnormalities than HIV-negative users or HIV-positive non-meth using individuals. Though Tat (an early RNA binding protein that regulates transcription) and methamphetamine independently do not have a toxic effect, their combination significantly increased cell death after 48 hours of exposure, inducing death of the human neuroblastoma cell line, SH-Sy5Y.²⁰  

One other study that should be mentioned hypothesises that meth has a synergistic effect when combined with Tat that damages basal ganglia, resulting in HIV-1 associated dementia (HAD), a form of subcortical dementia. This interaction results in exacerbated neuronal damage in rodent models and cell culture and also manifests in movement abnormalities, similar to those seen with Parkinson’s disease.²¹

These studies support earlier research suggesting that DNA damage caused by drug use leads to faster viral turnover and greater viral mutation. This may then contribute to the higher rates of neurological disease and drug resistance seen among HIV-infected injecting drug users.²²

Becoming HIV-infected through injection drug use has been associated with faster disease progression.²³ Using injecting drugs after seroconversion resulted in a 45% greater risk of disease progression than was found in non-users in a study of over 2000 individuals.²⁴ Although this is thought to be due to poorer adherence to antiretroviral therapy among drug users, other factors – including poor nutrition, poverty, and reduced access to healthcare – no doubt also contribute to faster disease progression.

Sharing needles to inject drugs runs the risk of re-exposure to HIV, as well as increasing the risk of introducing other infections into the body or causing septicaemia, a dangerous blood infection. Injecting drug users should be encouraged to stop injecting and either switch to methadone or stop using drugs altogether. This is a very difficult change to make at any time, but particularly so immediately following a diagnosis of HIV.

Marijuana use has been associated with an exacerbation of HIV-induced cognitive impairment, particularly memory impairment, in patients with advanced disease.²⁵  

Repeated exposure to HIV may accelerate disease progression. Frequent unprotected receptive anal intercourse has been associated with more rapid CD4 cell declines. The risk of CD4 T-cell loss increases with the number of partners with whom unprotected receptive anal intercourse is practised, although a small proportion of men who consistently report a high number of partners appear to be at a much lower risk of rapid CD4 decline.²⁶ It has not been determined if the cause of CD4 cell count decline is re-infection with HIV, exposure to other sexually transmitted infections, or some other factor.

In some of the documented cases of re-infection, also known as superinfection, control of HIV by the immune system or by therapy has been undermined, and disease progression has followed.

Most studies suggest that smoking does not affect the rate of HIV progression itself.²⁷ However, there is good evidence that it does increase the risk of opportunistic infections such as pneumocystis and community-acquired pneumonia, as well as kidney disease.^{28 29} 

Smokers have significantly less T-cell numbers and cytokine activity in their lungs than non-smokers, putting them at greater risk of lung infections. Smokers are three times more likely to develop pneumocystis pneumonia (PCP) than non-smokers, with the heaviest smokers at the highest risk. Smokers with HIV are at increased risk of developing emphysema, in which lung tissue is destroyed.³⁰ HIV-positive smokers were also found to have much higher levels of cytotoxic CD8 T-cells in their lung tissue, suggesting that damage may be caused by activity of immune cells in smokers. Smoking also increases the risk of developing bacterial pneumonia, oral hairy leukoplakia, and thrush in HIV-positive men. The heaviest smokers were at the greatest risk of developing these infections.

Women who smoke have a greater chance of passing HIV to their unborn children if not receiving antiretroviral treatment.³¹ It is thought that nicotine may cause premature rupture of membranes surrounding the foetus, increasing the potential exposure of the infant to HIV-infected blood during delivery.

Severe stress can accelerate HIV disease progression. A high frequency of stress events, such as the break-up of a long-term relationship, trouble at work, chronic financial difficulties, death of a loved one, or arrest have been associated with a fourfold increased risk of disease progression.³²

Levels of stress common to everyday living do not influence disease progression. Psychological distress has been associated with faster disease progression, but not a shorter survival time.³³ Many studies have found a relationship between psychosocial factors (lack of adequate social support, stressful life events, and depression) with staying on therapy and with disease progression.^{34 35}

People who receive their medical care from doctors experienced in AIDS live longer than those with less experienced doctors.³⁶ Patients of experienced physicians are more likely to receive primary care and special care services, as well as better access to pharmacy and laboratory services. This translates into improved survival.³⁷

The quality of the patient-physician relationship, meaning specifically that an individual feels the clinician 'knows them as a person', has also been significantly and independently associated with receiving HIV treatment, adhering to treatment, and having undetectable viral load.³⁸