Co-factors influence the speed of progression of disease without directly causing it, and without being necessary for the disease to occur. In AIDS there are several proven co-factors and more still under study.

Infection route

There is conflicting evidence on whether there is any difference in the risk of developing AIDS between people according to infection route. Studies which showed a faster rate of disease progression among those infected by blood transfusion may not have taken into account the older age of the blood transfusion recipients, which is in itself a risk factor for faster disease progression (Collaborative Group 2000).

There is conflicting evidence surrounding the rate of disease progression in injecting drug users. See Recreational drugs below for further information.

Age

There is faster overall progression to AIDS in adults with increasing age. The effect is more noticeable in people over the age of 40. It has been estimated that in adults the risk of developing AIDS may increase by between 27 and 55% for each ten-year increase in age. A study of almost 1220 haemophiliacs in the United Kingdom found that the proportion who remained alive ten years after infection was 86% for those aged under 15 when infected, 72% of those aged between 15 and 34, 45% for those aged between 35 and 54 and 12% for those over 55 (Darby 1996).

An Italian study found that the relative risk of disease progression increased 1.5-fold for every ten years. The age range of subjects in the study was 14 to 61 years, with the average age 25 amongst injecting drug users, 33 amongst gay men and 26 amongst heterosexual men and women (Pezzotti 1996).

A meta-analysis of data from 38 studies, comprising over 13,000 individuals, showed that age and time since seroconversion were the significant factors in determining the speed of disease progression. Median survival varied from 12.5 years for those aged between 15 and 24 years at seroconversion to 7.9 years for those aged between 45 and 54 years at seroconversion. Development of AIDS occurred after a median of 11.0 years and 7.7 years respectively (Collaborative Group 2000).

One explanation for this effect is that CD4 T-cells are more difficult to replace with increasing age, perhaps because of the loss of capacity of the thymus gland to generate new naive CD4 T-cells. For further discussion on the role of the thymus in HIV disease, see Immune restoration with anti-viral drugs in Anti-HIV therapy: Restoring the immune system.

The Italian researchers also suggested that there may be age-related differences in response to antiretroviral therapy, and that this should be controlled for in long-term clinical trials. Another possibility is that older people may have lower levels of chemokines whose presence can make it harder for HIV to infect CD4 T-cells. These are discussed in Immune responses to HIV in The immune system and HIV: How HIV damages the immune system earlier in this section.

The rate of disease progression is also faster among younger children, especially newborn HIV-positive babies. The slowest rate of progression to AIDS is seen in teenagers.

An unanswered question is the extent to which age influences the viral set-point after seroconversion. If, as has been suggested, younger people have a better immune response, one would expect to see a significant trend not merely towards slower disease progression but also towards a lower viral set-point. However, this data will not be available until longitudinal studies of viral burden have been carried out.

After starting antiretroviral therapy, older age remains a risk factor for disease progression. French cohort data show that risk of disease progression is generally lower among people who have not experienced an AIDS-defining event in the previous year. However, age over 50 and CD4 cell count below 200 cells/mm³ are associated with increased risk of progression in this group (Droz 2003).

However, a United States cohort study found that being aged over 50 was associated with a higher rate of achieving an undetectable viral load once starting combination antiretroviral therapy. People aged 50 or older also experienced similar levels of CD4 cell count increases and AIDS-defining illnesses as the younger members of the cohort. However, people aged 50 or more still had a significantly higher mortality, although the cause of death was not directly HIV-associated in the majority of patients (Moore 2004).

Ethnicity and location

Research from the United Kingdom does not support the view that Africans living in the United Kingdom develop AIDS and die more quickly than non-Africans, as has been suggested. A review of over 1050 Africans with HIV and 992 non-Africans diagnosed between 1982 and 1995 showed a similar median survival period of 82 and 78 months respectively, no significant difference in the rate of CD4 cell count decline, and no difference in rates of progression according to the treatment centre attended.

Although the study could not specifically investigate HIV-1 sub-type, the researchers suggested that it was highly likely that the African men and women studied would have been infected with different sub-types from the one normally found in gay men and injecting drugs users in Europe and North America. This suggests that outside Africa, these sub-types do not cause faster disease progression, and that it is environmental factors and lack of access to state of the art medical care in Africa which contribute to faster disease progression rates in Africa (Del Amo 1998).

Research in Uganda suggests that disease progression rates among Africans are similar to those seen in the industrialised world. The median time from exposure to an AIDS diagnosis was estimated at 9.4 years (Morgan 2002). Similarly, a study in the United States found no difference in viral load levels amongst different racial groups after controlling for CD4 cell count, access to medical care and socio-economic status. The study was conducted amongst military personnel, a racially mixed group homogenous in other respects.

However, there is evidence that a particular genetic mutation which occurs commonly among people of African descent may increase a person's risk of HIV infection and the speed of disease progression, as outlined below.

The progression from HIV infection to AIDS and death from AIDS is more rapid in untreated young men infected with HIV-1 subtype E living in Thailand than in HIV-positive individuals with HIV-1 subtype B infection living in the United States, Australia and Europe, with median times to the development of clinical AIDS being 7.4 and 11 years, respectively. In addition, the mortality rate of the Thai men was 18% five years after HIV-1 infection, as compared to a 9% among individuals living in developed countries in the West (Rangsin 2004).

Genetic susceptibility - receptors

People who have inherited certain mutant genes or polymorphisms may have CD4 cells that are less vulnerable to infection by HIV because they lack the co-receptors CCR5 or CXCR4, or because they express them in a different way. A polymorphism is a common specific difference in a gene between individuals that is not a mutation. Such polymorphisms usually result in the change of a single amino acid building block in the receptors protein structure.

A meta-analysis of over 2210 individuals with known seroconversion dates from eleven cohorts which reported 680 AIDS events in 14,700 person years found that the CCR5-Δ32 mutation was associated with a 23% lower risk of progression to AIDS, and the CCR2 64I polymorphism was associated with a 26% lower risk of disease progression (Ioannidis 2001). A second meta-analysis involving 1850 people found that CCR5-Δ32 reduced the risk of AIDS by 31% and the risk of death by 39% (Mulherin 2003).

The CCR2 64I polymorphism was associated with a significantly longer time to reach a CD4 cell count below 200 cells/mm³ in a group of 122 European patients (Easterbrook 1999). This polymorphism has been found to be more prevalent amongst Africans and Asians than amongst Europeans, whilst the CCR5-Δ32 mutation is largely confined to people of northern European descent. The CCR2 64I polymorphism has also been associated with an increased risk of male to female transmission of HIV (Lockett 2001).

However, the way in which such mutations impact on HIV disease appears to be more complex than first thought. The protective effect has been linked to duration of infection, younger age, and injecting drug use (Mulherin 2003; Iversen 2003). For example, CCR2 64I provides the greatest protection early in the course of HIV infection (Mulherin 2003; Ioannidis 2003). A study of disease progression among injecting drug users has found that the CCR5-Δ32 and the CCR2 64I mutations did not significantly affect progression to AIDS or CD4 cell count decline (Schinkel 1999).

Researchers have attempted to explain this observation in terms of the impact that injecting drug use may have on the immune system but the limited protective effect of CCR5-Δ32 in other cohorts suggests that other factors influence the protective effect of receptor mutations. One study investigating the relationship between age, CCR5-Δ32, CCR2-64I and a mutation called SDF-1 3A found that having a younger age or the CCR2-64I or SDF-1 3 A mutations were associated with higher CD4 cell counts. However SDF-1 3 A was also found to be associated with increased risk of developing AIDS (Geskus 2005).

A mutation on the CCR5 receptor called 356T makes CD4 T-cells more vulnerable to HIV infection. This mutation, which occurs in 20% of African Americans, and is common in people from west Africa, may increase the likelihood of transmission and the speed of disease progression. The chemokine receptor CX₃CR1 contains two known polymorphisms called T/M280 and V/I249. T/M280 has also been linked to accelerated HIV progression (Faure 2003). A study of the T/M280 and V/I249 polymorphism in children found that the amino acid isoleucine at position 249 of the receptor instead of valine was associated with more rapid disease progression. Children with valine at position 249 and threonine at position 280 instead of methionine experienced significantly slower disease progression (Singh 2005).

For more information, see Receptors, co-receptors and immunity to HIV in The immune system and HIV: How the immune system works.

Genetic susceptibility - chemical messengers

Genetic variations in cytokines and chemokines may also influence disease progression. One study of 337 slow and rapid progressors found that genetic variations of interleukin-4 and interleukin-10 affected the rate of disease progression (Vasilescu 2003). Similarly, levels of chemokines such as RANTES, MIP-1α and MIP-1β may also impact on HIV disease progression. The production of these chemokines is regulated by the production of interleukin-7 which may influence pathogenesis (Koning 2003; Llano 2003). Low copy number of the gene for a chemokine called CCL3L1 was fund to be associated with markedly increased risk of advanced disease progression (Mackay 2005).

For more details, Receptors, co-receptors and immunity to HIV in The immune system and HIV: How the immune system works.

Genetic susceptibility - human leukocyte antigens

There is a relationship between the genetic make-up of the immune system's antigen presenting molecules called human leukocyte antigens (HLAs) and HIV disease progression. HLAs are genetically inherited and play an important role in triggering immune responses. For a more detailed discussion of HLA, see Recognising antigens in The immune system and HIV: How the immune system works.

One study identified a six-fold difference in the time from infection with HIV to the development of AIDS between gay men with different HLA profiles. Other research has suggested that people with identical gene pairs for HLA-A and HLA-B progress to AIDS rapidly. These two tissue types are involved in the immune system's identification of infected cells and the CD8 T-cell response (Kaslow 1996; Tang 1999). Further evidence that a diverse range of HLA variations slows disease progression comes from American researchers. They have found that HIV adapts to the most frequent HLA alleles, providing an advantage to people with rare alleles. Dubbed HLA 'supertypes', these are associated with superior immune responses to HIV (Trachtenberg 2003).

French researchers have identified specific genes associated with slow or quick HIV progression. In particular, people with HLA class I genes B14 and C8 are likely to experience slow or non-progression of HIV, whereas those with HLA class I genes A29 and B22 are likely to experience rapid progression (Hendel 1999).

Australian researchers have also identified HLA variations associated with non-progression, particularly class I alleles A1, B14, B44, B27 and B57 or B5701 (Guerin 2003). Investigation of an elite group of long-term non-progressors found 11 of 13 had the B5701 variant. However, it seems that this variant is not the single determinant of non-progression, given that 19 of 200 progressors also had the B5701 variant (Migueles 2000). In contrast, rapid progression of HIV disease has been linked to HLA alleles B*54, B*55 and B*56 (Dorak 2003).

The mechanism by which HLA influences disease progression is not yet understood. Some researchers have suggested that particular HLA molecules may be directly involved in restricting HIV replication, while others have claimed that HLA molecules associated with slow disease progression may allow recognition of a wider range of viral antigens and a greater capacity for stimulating cytotoxic T-cell responses (Scherer 2004). More research is required to understand this process, in particular since the success of an eventual HIV vaccine may depend on the HLA type in the person being vaccinated.

A recent study has shown that children infected with HIV from their mothers, and who have inherited HLA alleles that normally are associated with slower disease progression are more likely to progress to AIDS or death than children who inherit them from their fathers (Kuhn 2004). This is probably because HIV in the mother has already evolved mechanisms to evade the effect of these HLA genes in the mother's body.

Genetic susceptibility - multi-drug transporters

The multidrug resistance transporter 1 (MDR1) gene has also been linked to speed of progression, although these reports have been controversial. MDR1 is the gene which produces P-glycoprotein (P-gp), a drug transport molecule present on the cell surface that protects cells from toxic chemicals such as cancer chemotherapies and HIV antiretrovirals by pumping them out of cells. Different MDR1 genes will produce different amounts of P-gp, and some reports have suggested that P-gp, even in the absence of therapy, might also play a role in how susceptible cells are to becoming infected with HIV.

However, a new study suggests this may not be the case. The study looked at the type and amount of MDR1 in T-cells taken from HIV-negative people and then exposed these cells to HIV in the laboratory. MDR1 and P-gp did not affect the cells' susceptibility to HIV infection. Furthermore, analysis of MDR1 in patients enrolled in the Swiss Cohort Study indicated that MDR1 variations may have a very slight effect on the rate of CD4 cell count decline over three years, but this was not statistically significant (Bleiber 2004).

Genetic susceptibility - other factors

The human protein APOBEC3G is a naturally-occurring antiviral protein that inhibits viral replication by altering the DNA molecules produced from HIV's genetic material by the reverse transcriptase gene. HIV can evade the action of this protein by producing the viral infectivity factor (Vif), which inhibits APOBEC3G's activity.

A recent study in over 3070 HIV-positive patients found that variations in the human APOBEC3G gene can affect the speed of HIV disease progression. One variant, H186R, was common in African Americans and was associated with a rapid decline in CD4 cell counts and the development of AIDS (An 2004).

Gender

Current thinking is that gender itself does not influence the risk of developing AIDS. However, there has been confusion about this issue because some studies have found an effect by gender which reflected measures of poverty and poor access to medical care among women.

A Swiss cohort study which looked at this question found no difference in AIDS survival rates between men and women. However, year of infection, female sex and injecting drug use were associated with faster CD4 cell count declines (Vanhems 1999). Women on average have a lower viral set-point than men but this does not seem to affect the rate of disease progression.

A New York study investigated disease progression children and found no differences between genders (Liu 2004).

Pregnancy

Most research suggests that pregnancy does not hasten HIV disease progression. For example, seven-year follow-up of 648 HIV-infected women in the United States found that multiple pregnancies were not associated with an increased risk of disease progression (Mayer 2003).

However other studies have provided equivocal findings. The Swiss Cohort study and the Swiss Collaborative HIV and Pregnancy Study compared 32 women with 416 control women. Although pregnant women had a higher rate of AIDS-defining events than the control women, this difference was not statistically significant. One AIDS defining event, recurrent bacterial pneumonia, was significantly more common among the group of women who had been pregnant. There is also evidence that viral load increases in the twelve weeks after giving birth, even in women on stable antiretroviral therapy, and that viral load gradually increases thereafter (Watts 2003).

Nutrition

It is well known that deficiencies in some vitamins and minerals and protein malnutrition can worsen immune function. There is now evidence that deficiencies of vitamins A and B₁₂ and zinc are associated with more rapid decline of CD4 cell counts.

Malabsorption, diarrhoea and poor intake of calories and proteins probably contribute to worsening HIV disease. For example, a study looking a prognostic markers of survival in children in Zambia found that malnutrition was the best clinical predictor of death in both HIV-negative and HIV-positive children (Sinyinza 2004).

Multivitamin supplementation has been shown to slow time to AIDS and death in a number of studies. One study, involving almost 1080 HIV-positive women in Tanzania showed that women receiving a supplement containing vitamins B₁, B₂, B₃, B₆, B₉, C and E reduced the likelihood of progression to AIDS or death, viral loads and HIV-related symptoms over up to eight years' follow-up, relative to placebo. However, the addition of vitamin A seemed to reduce the effect of the vitamin supplementation (Fawzi 2004).

A placebo controlled study in Thailand in 500 HIV-positive adults also showed that micronutrient supplementation reduced the risk of death over 48 weeks of follow-up by 70 to 80% in those with CD4 cell counts below 200 cells/mm³, although no impact was seen at CD4 counts above this level (Jiamton 2004). A similar study in patients in the United States taking antiretroviral therapy has also shown a beneficial effect of a broad-spectrum micronutrient formula on CD4 cell count increases (Kaiser 2004).

Stress

Severe stress can accelerate HIV disease progression, according to research from the United States. 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 over a two year period were associated with a four-fold increased risk of disease progression from asymptomatic illness. The study was conducted amongst 93 gay men aged 18 to 51 who were asymptomatic when they entered the study. Users of recreational drugs and heavy users of alcohol were excluded from the study, and researchers excluded disease related stress from their analysis in order to differentiate between the effects of developing symptoms on the immune system and other stress-related changes (Evans 1997).

Levels of stress common to everyday living did not influence disease progression. However, one study found that HIV disease progression was accelerated in men who experienced stress but who had inadequate social support (Leserman 1999).

Psychological distress, as assessed by an eleven-point scale, was also found to be associated with faster disease progression, but not a shorter survival time in 451 injecting drug users in the ALIVE cohort between 1988 and 1999. After controlling for baseline CD4 cell count, development of oral thrush and HIV viral load at baseline, psychological distress was found to be predictive of the development of an AIDS-defining illness within two years (Golub 2003).

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 (Easterbrook 1996). Similarly, a longitudinal study involving only HIV-positive women found that lifestyle factors did not affect risk of progression over seven years (Mayer 2003).

Unprotected intercourse - re-infection with HIV or sexually transmitted infections?

There is some evidence that repeated exposure to HIV accelerates disease progression.

A five-year study of 937 HIV-positive men receiving little or no antiretroviral treatment has shown that those who had unprotected receptive anal intercourse had more rapid CD4 cell declines than men who avoided it. The men who reported unprotected intercourse during the previous twelve months were twice as likely to experience a CD4 cell count decline compared those who did not. The risk of CD4 T-cell loss increased with the number of partners with whom they had had unprotected receptive anal intercourse, although a small number of men who consistently reported a high number of partners were at much lower risk of rapid CD4 decline (Wiley 2000). However, this study could not determine whether the cause of the CD4 cell count decline was re-infection with HIV, exposure to other sexually transmitted infections, or some immunosuppressive effect of semen itself.

Several cases of re-infection have been documented. In some cases re-infection, also known as superinfection, has undermined control of HIV by the immune system or treatments, and disease progression has followed. See the Transmission of resistant HIV in Anti-HIV therapy: Resistance for further information.

Smoking

Most studies suggest that smoking does not affect the rate of HIV progression itself, such as the speed at which the CD4 count falls or how rapidly AIDS is diagnosed (Galai 1997). However, there is good evidence that it increases the risk from certain opportunistic infections.

Although smokers have a slightly higher blood CD4 cell counts than non-smokers, analysis of immune cells in the lung fluid has shown that CD4 and CD8 percentages and cytokine activity are significantly reduced in smokers, putting them at greater risk of lung infections. For example, a large review of 598 HIV-positive people found that smokers were three times more likely to have developed Pneumocystis pneumonia (PCP) than non-smokers, with the heaviest smokers at highest risk (Buskin 1992).

Smokers with HIV are significantly more likely to develop the lung condition emphysema than HIV-negative smokers. Emphysema is a condition in which lung tissue is destroyed, possibly by immune system reactions. In one study, 15% of HIV-positive patients had emphysema, compared with 2% of the HIV-negative group, and in people who had smoked for 12 years or more, the difference was even more striking: 37% of the long-term HIV-positive smokers had evidence of emphysema, whilst none of the long-term HIV-negative smokers had signs of emphysema. The average age of the HIV-positive patients was 34, indicating very early onset of smoking-related emphysema (Diaz 2000). HIV-positive smokers were also found to have much higher levels of cytotoxic CD8 T-cells in their lung tissue, suggesting that some of the damage may have been caused by these immune cells.

In the general population, smoking is a risk factor for Candida (thrush) in the mouth. However, one study found that although smoking increased the number of Candida organisms detectable in swabs from the mouth, it did not seem to increase the risk of developing symptoms of candidiasis (Nittayananta 1994). Another study conducted in the United States found that smoking did increase the risk of developing bacterial pneumonia, oral hairy leukoplakia and thrush in HIV-positive men, but did not increase the risk of developing PCP. The heaviest smokers were at the greatest risk of developing these infections (Conley 1996). Similar results were seen in another study (Burns 1996).

Women who smoke have a greater chance of passing HIV to their unborn children, according to a study of women with HIV who gave birth between 1988 and 1990, before the introduction of antiretroviral treatment to reduce the risk of mother to baby transmission (Turner 1997). One third of women who smoked transmitted HIV to their babies, compared with less than one in four of women who did not smoke. It has been suggested that nicotine may cause premature rupture of membranes surrounding the foetus, increasing the period of time during which an infant may potentially be exposed to HIV-infected blood during delivery.

There is also evidence that smoking can increase the risk of HIV-positive patients developing kidney disease (Miguez-Burbano 2004).

Recreational drugs

Most research indicates that recreational drug use does not affect HIV disease progression. A review of the literature conducted in 1994 concluded that there is little evidence that active drug injection is detrimental to the outcome of HIV infection (Phillips 1994). However, there have been studies that suggest that HIV-positive drug users who continue to inject heroin may develop AIDS faster than those who use other drugs or give up drugs (Ronald 1994). A New York study of almost 1150 women, 40% of whom reported use of cocaine, heroin, methadone, or injecting drugs, found there was no associated change in CD4 cell percentage, viral loads or death of any cause. An increased risk of certain types of nonfatal infections was found, however, namely herpes, tuberculosis and recurrent pneumonia (Thorpe 2004).

There is some evidence that drug use may, directly or indirectly, contribute to disease progression. In particular, studies have suggested that cocaine may accelerate HIV disease progression by increasing HIV replication. Research has shown that cocaine boosts the ability of HIV to infect immune system cells by suppressing the production of cytokines, such as MIP-1beta. This enhances the expression of CCR5 receptors, the co-receptors used by HIV to infect cells most of the duration of HIV infection (Nair 2000).

This finding confirms previous reports which linked cocaine use with accelerated disease progression. For instance, a study of 370 gay men in San Francisco has found that weekly use of hallucinogens and cocaine were associated with increased risk of death, although this study did not explore a causal connection (Vittinghoff 2001).

Methamphetamine has also been investigated for its potential effect on HIV viral load. One study of methamphetamine in 230 HIV-positive people found that users of methamphetamine who were taking antiretroviral therapy had higher viral load than non-users. However, there was no significant impact of methamphetamine on viral load in the absence of antiretroviral therapy. This suggests that impact on viral load may be a result of poor adherence to treatment, rather than a direct effect of the drug (Ellis 2003). Methamphetamine may also boost turnover of HIV (Gavrilin 2002) or accelerate brain damage (Langford 2003) although none of these claims has been definitively proven.

Injecting drug use itself is not thought to increase disease progression, although research has provided contradictory findings. Some experts have suggested 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 (Madden 2002). A study of over 2000 people found that injecting drug users were at a 45% greater risk of disease progression than non-users (Moore 2004). Although this is thought to be due to poorer adherence to antiretroviral therapy among drug users, other factors such as poor immune response, poor nutrition, poverty and reduced access to healthcare may be contributing to speedier 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 may be encouraged to stop injecting and to switch over to methadone, or to stop using drugs altogether. These forms of stress may be very difficult to deal with, particularly if they come immediately after a diagnosis of HIV.

There is also test-tube evidence that alcohol may accelerate HIV progression. By blocking a chemical messenger in the immune system and stimulating expression of the CCR5 co-receptor which HIV uses to infect cells, alcohol may boost HIV infection of cells (Wang 2002). This has been followed by observations that monkeys given high doses of alcohol over long periods of time have higher viral loads soon after infection, due to the drug's effects on immune cells in the intestine^[1][2][3]. However, studies in people have not found an association between alcohol consumption and HIV disease progression to date.

Marijuana use has been associated with an exacerbation of HIV-induced cognitive impairment, particularly in memory impairment, in patients with advanced disease (Cristiani 2004).

Some people have argued that poppers (inhaled nitrites) can suppress the immune system. Several studies have now been conducted to look at the effects of nitrites on the immune systems of mice and humans, with inconclusive results. While early studies in mice showed reductions in white blood cell counts with low doses, very high doses of inhaled nitrites caused serious impairment of T-cell functions and the ability of their macrophages to control the development of potential tumours. Critics of this study point out that the mice were exposed to huge amounts of nitrites.

The only study to have taken place in humans gave normal doses of nitrites to HIV-negative men three times a day for one week and then intermittently for a further one and a half weeks. By the end of this period the main defect in immune function was in the level of natural killer (NK) cells, which recognise and destroy a wide range of infected body cells or tumour cells. Levels of T-lymphocytes were not seriously affected and there was no selective effect on any sub groups of T-lymphocytes. No studies have yet demonstrated that alterations in NK cell levels correlate with any of the illnesses experienced by people with HIV.

Doctor's experience

While not strictly a co-factor, studies have found that people who receive their medical care from doctors experienced in AIDS tend to live longer than those with less experienced doctors. In one study, the risk of death among people with AIDS was 43% lower among those with the most experienced doctors compared with those with the least experienced doctors (Kitahata 1996).

Subsequent work by the same author has found that patients of experienced physicians are more likely to receive primary care and special care services, and that they receive better access to pharmacy and laboratory services. This translates into improved survival (Kitahata 2003).

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