Vascular pressure wave

Modern physiology developed the concept of the vascular pressure wave (VPW). This wave is created by the heart during the systole and originates in the ascending aorta. Much faster than the stream of blood itself, it is then transported through the vessel walls to the peripheral arteries. There the pressure wave can be palpated as the peripheral pulse. As the wave is reflected at the peripheral veins it runs back in a centripetal fashion. Where the crests of the reflected and the original wave meet, the pressure inside the vessel is higher than the true pressure in the aorta. This concept explains why the arterial pressure inside the peripheral arteries of the legs and arms is higher than the arterial pressure in the aorta, and in turn for the higher pressures seen at the ankle compared to the arm with normal ankle brachial pressure index values.

AIDS denialism

Main article: AIDS denialism

A small number of activists question the connection between HIV and AIDS, the existence of HIV, or the validity of current treatment methods (even going so far as to claim that the drug therapy itself was the cause of AIDS deaths). Though these claims have been examined and thoroughly rejected by the scientific community, they continue to be promulgated through the Internet and have had a significant political impact. In South Africa, former President Thabo Mbeki's embrace of AIDS denialism resulted in an ineffective governmental response to the AIDS epidemic that has been blamed for hundreds of thousands of AIDS-related deaths.

Economic impact

Changes in life expectancy in some hard-hit African countries. Botswana Zimbabwe Kenya South Africa Uganda

HIV and AIDS affects economic growth by reducing the availability of human capital.^[8] Without proper nutrition, health care and medicine that is available in developed countries, large numbers of people suffer and die from AIDS-related complications. They will not only be unable to work, but will also require significant medical care. The forecast is that this will probably cause a collapse of economies and societies in countries with a significant AIDS population. In some heavily infected areas, the epidemic has left behind many orphans cared for by elderly grandparents.

The increased mortality in this region will result in a smaller skilled population and labor force. This smaller labor force will be predominantly young people, with reduced knowledge and work experience leading to reduced productivity. An increase in workers’ time off to look after sick family members or for sick leave will also lower productivity. Increased mortality will also weaken the mechanisms that generate human capital and investment in people, through loss of income and the death of parents. By killing off mainly young adults, AIDS seriously weakens the taxable population, reducing the resources available for public expenditures such as education and health services not related to AIDS resulting in increasing pressure for the state's finances and slower growth of the economy. This results in a slower growth of the tax base, an effect that will be reinforced if there are growing expenditures on treating the sick, training (to replace sick workers), sick pay and caring for AIDS orphans. This is especially true if the sharp increase in adult mortality shifts the responsibility and blame from the family to the government in caring for these orphans.

On the level of the household, AIDS results in both the loss of income and increased spending on healthcare by the household. The income effects of this lead to spending reduction as well as a substitution effect away from education and towards healthcare and funeral spending. A study in Côte d'Ivoire showed that households with an HIV/AIDS patient spent twice as much on medical expenses as other households.

Stigma

Ryan White became a poster child for HIV after being expelled from school because of his infection.

AIDS stigma exists around the world in a variety of ways, including ostracism, rejection, discrimination and avoidance of HIV infected people; compulsory HIV testing without prior consent or protection of confidentiality; violence against HIV infected individuals or people who are perceived to be infected with HIV; and the quarantine of HIV infected individuals.Stigma-related violence or the fear of violence prevents many people from seeking HIV testing, returning for their results, or securing treatment, possibly turning what could be a manageable chronic illness into a death sentence and perpetuating the spread of HIV.

AIDS stigma has been further divided into the following three categories:

• Instrumental AIDS stigma—a reflection of the fear and apprehension that are likely to be associated with any deadly and transmissible illness.
• Symbolic AIDS stigma—the use of HIV/AIDS to express attitudes toward the social groups or lifestyles perceived to be associated with the disease.
• Courtesy AIDS stigma—stigmatization of people connected to the issue of HIV/AIDS or HIV- positive people.

Often, AIDS stigma is expressed in conjunction with one or more other stigmas, particularly those associated with homosexuality, bisexuality, promiscuity, prostitution, and intravenous drug use.

In many developed countries, there is an association between AIDS and homosexuality or bisexuality, and this association is correlated with higher levels of sexual prejudice such as anti-homosexual attitudes. There is also a perceived association between AIDS and all male-male sexual behavior, including sex between uninfected men.

AIDS

AIDS was first reported June 5, 1981, when the U.S. Centers for Disease Control (CDC) recorded a cluster of Pneumocystis carinii pneumonia (now still classified as PCP but known to be caused by Pneumocystis jirovecii) in five homosexual men in Los Angeles. In the beginning, the CDC did not have an official name for the disease, often referring to it by way of the diseases that were associated with it, for example, lymphadenopathy, the disease after which the discoverers of HIV originally named the virus. They also used Kaposi's Sarcoma and Opportunistic Infections, the name by which a task force had been set up in 1981. In the general press, the term GRID, which stood for Gay-related immune deficiency, had been coined. The CDC, in search of a name, and looking at the infected communities coined “the 4H disease,” as it seemed to single out Haitians, homosexuals, hemophiliacs, and heroin users. However, after determining that AIDS was not isolated to the homosexual community, the term GRID became misleading and AIDS was introduced at a meeting in July 1982. By September 1982 the CDC started using the name AIDS, and properly defined the illness.

A more controversial theory known as the OPV AIDS hypothesis suggests that the AIDS epidemic was inadvertently started in the late 1950s in the Belgian Congo by Hilary Koprowski's research into a poliomyelitis vaccine. According to scientific consensus, this scenario is not supported by the available evidence.

A recent study states that HIV probably moved from Africa to Haiti and then entered the United States around 1969.

Epidemiology

Estimated prevalence of HIV among young adults (15–49) per country at the end of 2005

The AIDS pandemic can also be seen as several epidemics of separate subtypes; the major factors in its spread are sexual transmission and vertical transmission from mother to child at birth and through breast milk. Despite recent, improved access to antiretroviral treatment and care in many regions of the world, the AIDS pandemic claimed an estimated 2.1 million (range 1.9–2.4 million) lives in 2007 of which an estimated 330,000 were children under 15 years.^[7] Globally, an estimated 33.2 million people lived with HIV in 2007, including 2.5 million children. An estimated 2.5 million (range 1.8–4.1 million) people were newly infected in 2007, including 420,000 children.

Sub-Saharan Africa remains by far the worst affected region. In 2007 it contained an estimated 68% of all people living with AIDS and 76% of all AIDS deaths, with 1.7 million new infections bringing the number of people living with HIV to 22.5 million, and with 11.4 million AIDS orphans living in the region. Unlike other regions, most people living with HIV in sub-Saharan Africa in 2007 (61%) were women. Adult prevalence in 2007 was an estimated 5.0%, and AIDS continued to be the single largest cause of mortality in this region. South Africa has the largest population of HIV patients in the world, followed by Nigeria and India. South & South East Asia are second worst affected; in 2007 this region contained an estimated 18% of all people living with AIDS, and an estimated 300,000 deaths from AIDS. India has an estimated 2.5 million infections and an estimated adult prevalence of 0.36%. Life expectancy has fallen dramatically in the worst-affected countries; for example, in 2006 it was estimated that it had dropped from 65 to 35 years in Botswana.

In the United States, young African-American women are also at unusually high risk for HIV infection. This is due in part to a lack of information about AIDS and a perception that they are not vulnerable, as well as to limited access to health-care resources and a higher likelihood of sexual contact with at-risk male sexual partners. There are also geographic disparities in AIDS prevalence in the United States, where it is most common in rural areas and in the southern states, particularly in the Appalachian and Mississippi Delta regions and along the border with Mexico.

Prognosis

Without treatment, the net median survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype, and the median survival rate after diagnosis of AIDS in resource-limited settings where treatment is not available ranges between 6 and 19 months, depending on the study. In areas where it is widely available, the development of HAART as effective therapy for HIV infection and AIDS reduced the death rate from this disease by 80%, and raised the life expectancy for a newly diagnosed HIV-infected person to about 20 years.

As new treatments continue to be developed and because HIV continues to evolve resistance to treatments, estimates of survival time are likely to continue to change. Without antiretroviral therapy, death normally occurs within a year. Most patients die from opportunistic infections or malignancies associated with the progressive failure of the immune system. The rate of clinical disease progression varies widely between individuals and has been shown to be affected by many factors such as host susceptibility and immune function health care and co-infections, as well as which particular strain of the virus is involved.

Alternative medicine

Various forms of alternative medicine have been used to treat symptoms or alter the course of the disease. Current studies indicate that alternative medicine therapies have little effect on the mortality or morbidity of the disease, but may improve the quality of life of individuals with AIDS. The psychological benefits of these therapies are the most important use. Acupuncture has been used to alleviate some symptoms with no success and cannot cure the HIV infection.Several randomized clinical trials testing the effect of herbal medicines have shown that there is no evidence that these herbs have any effect on the progression of the disease, but may instead produce serious side-effects.

Morbidity and mortality among HIV-infected adults with adequate dietary nutritional intake is unaffected by multivitamin supplementation. A large Tanzanian trial in immunologically and nutritionally compromised pregnant and lactating women showed a number of benefits to daily multivitamin supplementation for both mothers and children. Dietary intake of micronutrients at RDA levels by HIV-infected adults is recommended by the World Health Organization.There is some evidence that vitamin A supplementation in children reduces mortality and improves growth. Daily doses of selenium can suppress HIV viral burden with an associated improvement of the CD4 count. Selenium can be used as an adjunct therapy to standard antiviral treatments, but cannot itself reduce mortality and morbidity.

Experimental and proposed treatments

It has been postulated that only a vaccine can halt the pandemic because a vaccine would possibly cost less, thus being affordable for developing countries, and would not require daily treatments. However, even after almost 30 years of research, HIV-1 remains a difficult target for a vaccine.

Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage drug resistance. A number of studies have shown that measures to prevent opportunistic infections can be beneficial when treating patients with HIV infection or AIDS. Vaccination against hepatitis A and B is advised for patients who are not infected with these viruses and are at risk of becoming infected. Patients with substantial immunosuppression are also advised to receive prophylactic therapy for Pneumocystis jiroveci pneumonia (PCP), and many patients may benefit from prophylactic therapy for toxoplasmosis and Cryptococcus meningitis as well.

Researchers have discovered an abzyme that can destroy the protein gp120 CD4 binding site. This protein is common to all HIV variants as it is the attachment point for B lymphocytes and subsequent compromising of the immune system.

In Berlin, Germany, a 42-year-old leukemia patient infected with HIV for more than a decade was given an experimental transplant of bone marrow with cells that contained an unusual natural variant of the CCR5 cell-surface receptor. This CCR5-Δ32 variant has been shown to make some cells from people who are born with it resistant to infection with some strains of HIV. Almost two years after the transplant, and even after the patient reportedly stopped taking antiretroviral medications, HIV has not been detected in the patient's blood.

Antiviral therapy

Current treatment for HIV infection consists of highly active antiretroviral therapy, or HAART. This has been highly beneficial to many HIV-infected individuals since its introduction in 1996 when the protease inhibitor-based HAART initially became available. Current optimal HAART options consist of combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of antiretroviral agents. Typical regimens consist of two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, particularly for young infants, treatment recommendations are more aggressive for children than for adults. In developed countries where HAART is available, doctors assess the viral load, rapidity in CD4 decline, and patient readiness while deciding when to recommend initiating treatment.

Standard goals of HAART include improvement in the patient’s quality of life, reduction in complications, and reduction of HIV viremia below the limit of detection, but it does not cure the patient of HIV nor does it prevent the return, once treatment is stopped, of high blood levels of HIV, often HAART resistant.^[107][108] Moreover, it would take more than the lifetime of an individual to be cleared of HIV infection using HAART.^[109] Despite this, many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to the plummeting of HIV-associated morbidity and mortality.^{[110][111][112]} In the absence of HAART, progression from HIV infection to AIDS occurs at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2 months. HAART is thought to increase survival time by between 4 and 12 years.

For some patients, which can be more than fifty percent of patients, HAART achieves far less than optimal results, due to medication intolerance/side effects, prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV. Non-adherence and non-persistence with therapy are the major reasons why some people do not benefit from HAART.^[115] The reasons for non-adherence and non-persistence are varied. Major psychosocial issues include poor access to medical care, inadequate social supports, psychiatric disease and drug abuse. HAART regimens can also be complex and thus hard to follow, with large numbers of pills taken frequently. Side effects can also deter people from persisting with HAART, these include lipodystrophy, dyslipidaemia, diarrhoea, insulin resistance, an increase in cardiovascular risks and birth defects. Anti-retroviral drugs are expensive, and the majority of the world's infected individuals do not have access to medications and treatments for HIV and AIDS.

Treatment

Abacavir – a nucleoside analog reverse transcriptase inhibitor (NARTI or NRTI)

The chemical structure of Abacavir

There is currently no publicly available vaccine for HIV or cure for HIV or AIDS. The only known methods of prevention are based on avoiding exposure to the virus or, failing that, an antiretroviral treatment directly after a highly significant exposure, called post-exposure prophylaxis (PEP). PEP has a very demanding four week schedule of dosage. It also has very unpleasant side effects including diarrhea, malaise, nausea and fatigue.

Exposure to infected body fluids

Health care workers can reduce exposure to HIV by employing precautions to reduce the risk of exposure to contaminated blood. These precautions include barriers such as gloves, masks, protective eyeware or shields, and gowns or aprons which prevent exposure of the skin or mucous membranes to blood borne pathogens. Frequent and thorough washing of the skin immediately after being contaminated with blood or other bodily fluids can reduce the chance of infection. Finally, sharp objects like needles, scalpels and glass, are carefully disposed of to prevent needlestick injuries with contaminated items. Since intravenous drug use is an important factor in HIV transmission in developed countries, harm reduction strategies such as needle-exchange programmes are used in attempts to reduce the infections caused by drug abuse.

Prevention and Sexual contact

Prevention

Estimated per act risk for acquisition
of HIV by exposure route

Exposure Route	Estimated infections per 10,000 exposures to an infected source
Blood Transfusion	9,000
Childbirth (to child)	2,500
Needle-sharing injection drug use	67
Percutaneous needle stick	30
Receptive anal intercourse*	50
Insertive anal intercourse*	6.5
Receptive penile-vaginal intercourse*	10
Insertive penile-vaginal intercourse*	5
Receptive oral intercourse*§	1
Insertive oral intercourse*§	0.5
* assuming no condom use § source refers to oral intercourse performed on a man

The three main transmission routes of HIV are sexual contact, exposure to infected body fluids or tissues, and from mother to fetus or child during perinatal period. It is possible to find HIV in the saliva, tears, and urine of infected individuals, but there are no recorded cases of infection by these secretions, and the risk of infection is negligible.

Sexual contact

The majority of HIV infections are acquired through unprotected sexual relations between partners, one of whom has HIV. The primary mode of HIV infection worldwide is through sexual contact between members of the opposite sex.

During a sexual act, only male or female condoms can reduce the chances of infection with HIV and other STDs and the chances of becoming pregnant. The best evidence to date indicates that typical condom use reduces the risk of heterosexual HIV transmission by approximately 80% over the long-term, though the benefit is likely to be higher if condoms are used correctly on every occasion.

The male latex condom, if used correctly without oil-based lubricants, is the single most effective available technology to reduce the sexual transmission of HIV and other sexually transmitted infections. Manufacturers recommend that oil-based lubricants such as petroleum jelly, butter, and lard not be used with latex condoms, because they dissolve the latex, making the condoms porous. If necessary, manufacturers recommend using water-based lubricants.

Oil-based lubricants can however be used with polyurethane condoms.

The female condom is an alternative to the male condom and is made from polyurethane, which allows it to be used in the presence of oil-based lubricants. They are larger than male condoms and have a stiffened ring-shaped opening, and are designed to be inserted into the vagina.

The female condom contains an inner ring, which keeps the condom in place inside the vagina – inserting the female condom requires squeezing this ring. However, at present availability of female condoms is very low and the price remains prohibitive for many women.

Preliminary studies suggest that, where female condoms are available, overall protected sexual acts increase relative to unprotected sexual acts, making them an important HIV prevention strategy.

Studies on couples where one partner is infected show that with consistent condom use, HIV infection rates for the uninfected partner are below 1% per year. Prevention strategies are well-known in developed countries, but epidemiological and behavioral studies in Europe and North America suggest that a substantial minority of young people continue to engage in high-risk practices despite HIV/AIDS knowledge, underestimating their own risk of becoming infected with HIV.

Randomized controlled trials have shown that male circumcision lowers the risk of HIV infection among heterosexual men by up to 60%. It is expected that this procedure will be actively promoted in many of the countries affected by HIV, although doing so will involve confronting a number of practical, cultural and attitudinal issues. However, programs to encourage condom use, including providing them free to those in poverty, are estimated to be 95 times more cost effective than circumcision at reducing the rate of HIV in sub-Saharan Africa.

Some experts fear that a lower perception of vulnerability among circumcised men may result in more sexual risk-taking behavior, thus negating its preventive effects. However, one randomized controlled trial indicated that adult male circumcision was not associated with increased HIV risk behavior.

HIV test

Many people are unaware that they are infected with HIV. Less than 1% of the sexually active urban population in Africa has been tested, and this proportion is even lower in rural populations. Furthermore, only 0.5% of pregnant women attending urban health facilities are counseled, tested or receive their test results. Again, this proportion is even lower in rural health facilities. Therefore, donor blood and blood products used in medicine and medical research are screened for HIV.

HIV tests are usually performed on venous blood. Many laboratories use fourth generation screening tests which detect anti-HIV antibody (IgG and IgM) and the HIV p24 antigen. The detection of HIV antibody or antigen in a patient previously known to be negative is evidence of HIV infection. Individuals whose first specimen indicates evidence of HIV infection will have a repeat test on a second blood sample to confirm the results.

The window period (the time between initial infection and the development of detectable antibodies against the infection) can vary since it can take 3–6 months to seroconvert and to test positive. Detection of the virus using polymerase chain reaction (PCR) during the window period is possible, and evidence suggests that an infection may often be detected earlier than when using a fourth generation EIA screening test.

Positive results obtained by PCR are confirmed by antibody tests. Routinely used HIV tests for infection in neonates and infants (ie, patients younger than 2 years), born to HIV-positive mothers, have no value because of the presence of maternal antibody to HIV in the child's blood. HIV infection can only be diagnosed by PCR, testing for HIV pro-viral DNA in the children's lymphocytes.

CDC classification system

There are two main definitions for AIDS, both produced by the Centers for Disease Control and Prevention (CDC). The older definition is to referring to AIDS using the diseases that were associated with it, for example, lymphadenopathy, the disease after which the discoverers of HIV originally named the virus. In 1993, the CDC expanded their definition of AIDS to include all HIV positive people with a CD4⁺ T cell count below 200 per µL of blood or 14% of all lymphocytes. The majority of new AIDS cases in developed countries use either this definition or the pre-1993 CDC definition. The AIDS diagnosis still stands even if, after treatment, the CD4⁺

T cell count rises to above 200 per µL of blood or other AIDS-defining illnesses are cured.

WHO disease staging system

WHO Disease Staging System for HIV Infection and Disease

In 1990, the World Health Organization (WHO) grouped these infections and conditions together by introducing a staging system for patients infected with HIV-1. An update took place in September 2005. Most of these conditions are opportunistic infections that are easily treatable in healthy people.

• Stage I: HIV infection is asymptomatic and not categorized as AIDS
• Stage II: includes minor mucocutaneous manifestations and recurrent upper respiratory tract infections
• Stage III: includes unexplained chronic diarrhea for longer than a month, severe bacterial infections and pulmonary tuberculosis
• Stage IV: includes toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi or lungs and Kaposi's sarcoma; these diseases are indicators of AIDS.

Diagnosis

The diagnosis of AIDS in a person infected with HIV is based on the presence of certain signs or symptoms. Since June 5, 1981, many definitions have been developed for epidemiological surveillance such as the Bangui definition and the 1994 expanded World Health Organization AIDS case definition. However, clinical staging of patients was not an intended use for these systems as they are neither sensitive, nor specific. In developing countries, the World Health Organization staging system for HIV infection and disease, using clinical and laboratory data, is used and in developed countries, the Centers for Disease Control (CDC) Classification System is used.

The effect

The virus has cytopathic effects but how it does it is still not quite clear. It can remain inactive in these cells for long periods, though. This effect is hypothesized to be due to the CD₄-gp120 interaction.

• The most prominent effect of the HIV virus is its T-helper cell suppression and lysis. The cell is simply killed off or deranged to the point of being function-less (they do not respond to foreign antigens). The infected B-cells can not produce enough antibodies either. Thus the immune system collapses leading to the familiar AIDS complications, like infections and neoplasms (vide supra).
• Infection of the cells of the CNS cause acute aseptic meningitis, subacute encephalitis, vacuolar myelopathy and peripheral neuropathy. Later it leads to even AIDS dementia complex.
• The CD₄-gp120 interaction (see above) is also permissive to other viruses like Cytomegalovirus, Hepatitis virus, Herpes simplex virus, etc. These viruses lead to further cell damage i.e. cytopathy.

Cells affected

The virus, entering through which ever route, acts primarily on the following cells:

• Lymphoreticular system:
  • CD₄+ T-Helper cells
  • Macrophages
  • Monocytes
  • B-lymphocytes
• Certain endothelial cells
• Central nervous system:
  • Microglia of the nervous system
  • Astrocytes
  • Oligodendrocytes
  • Neurones – indirectly by the action of cytokines and the gp-120

Pathophysiology

The pathophysiology of AIDS is complex, as is the case with all syndromes. Ultimately, HIV causes AIDS by depleting CD4⁺ T helper lymphocytes. This weakens the immune system and allows opportunistic infections. T lymphocytes are essential to the immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4⁺ T cell depletion differs in the acute and chronic phases.

During the acute phase, HIV-induced cell lysis and killing of infected cells by cytotoxic T cells accounts for CD4⁺ T cell depletion, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4⁺ T cell numbers.

Although the symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of CD4⁺ T cell loss occurs during the first weeks of infection, especially in the intestinal mucosa, which harbors the majority of the lymphocytes found in the body. The reason for the preferential loss of mucosal CD4⁺ T cells is that a majority of mucosal CD4⁺ T cells express the CCR5 coreceptor, whereas a small fraction of CD4⁺ T cells in the bloodstream do so.

HIV seeks out and destroys CCR5 expressing CD4⁺ cells during acute infection. A vigorous immune response eventually controls the infection and initiates the clinically latent phase. However, CD4⁺ T cells in mucosal tissues remain depleted throughout the infection, although enough remain to initially ward off life-threatening infections.

Continuous HIV replication results in a state of generalized immune activation persisting throughout the chronic phase. Immune activation, which is reflected by the increased activation state of immune cells and release of proinflammatory cytokines, results from the activity of several HIV gene products and the immune response to ongoing HIV replication. Another cause is the breakdown of the immune surveillance system of the mucosal barrier caused by the depletion of mucosal CD4⁺ T cells during the acute phase of disease.

This results in the systemic exposure of the immune system to microbial components of the gut’s normal flora, which in a healthy person is kept in check by the mucosal immune system. The activation and proliferation of T cells that results from immune activation provides fresh targets for HIV infection. However, direct killing by HIV alone cannot account for the observed depletion of CD4⁺ T cells since only 0.01–0.10% of CD4⁺ T cells in the blood are infected.

A major cause of CD4⁺ T cell loss appears to result from their heightened susceptibility to apoptosis when the immune system remains activated. Although new T cells are continuously produced by the thymus to replace the ones lost, the regenerative capacity of the thymus is slowly destroyed by direct infection of its thymocytes by HIV. Eventually, the minimal number of CD4⁺ T cells necessary to maintain a sufficient immune response is lost, leading to AIDS