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and recognized by Gag and Rev proteins. The SLIP element (TTTTTT) is involved in the

frameshift in the Gag-Pol reading frame required to make functional Pol.[53]

Tropism

Main article: HIV tropism

The term viral tropismrefers to which cell types HIV infects. HIV can infect a variety ofimmune cells such as CD4 + T cells , macrophages, and microglial cells. HIV-1 entry to

macrophages and CD4+ T cells is mediated through interaction of the virion envelope

glycoproteins (gp120) with the CD4 molecule on the target cells and also with chemokine

coreceptors.[54]

Macrophage (M-tropic) strains of HIV-1, or non-syncitia-inducing strains (NSI) use the

-chemokine receptorCCR5 for entry and are thus able to replicate in macrophages and

CD4+ T cells.[61] This CCR5 coreceptor is used by almost all primary HIV-1 isolates

regardless of viral genetic subtype. Indeed, macrophages play a key role in severalcritical aspects of HIV infection. They appear to be the first cells infected by HIV and

perhaps the source of HIV production when CD4+ cells become depleted in the patient.

Macrophages and microglial cells are the cells infected by HIV in thecentral nervoussystem. In tonsils and adenoids of HIV-infected patients, macrophages fuse into

multinucleated giant cells that produce huge amounts of virus.

T-tropic isolates, orsyncitia-inducing (SI) strains replicate in primary CD4+ T cells as

well as in macrophages and use the -chemokine receptor,CXCR4, for entry.[61][62][63]

Dual-tropic HIV-1 strains are thought to be transitional strains of HIV-1 and thus are able

to use both CCR5 and CXCR4 as co-receptors for viral entry.

The -chemokine SDF-1, a ligand for CXCR4, suppresses replication of T-tropic HIV-1

isolates. It does this by down-regulating the expression of CXCR4 on the surface of thesecells. HIV that use only the CCR5 receptor are termedR5; those that only use CXCR4

are termed X4, and those that use both, X4R5. However, the use of coreceptor alone does

not explain viral tropism, as not all R5 viruses are able to use CCR5 on macrophages fora productive infection[61] and HIV can also infect a subtype ofmyeloid dendritic cells,[64]

which probably constitute a reservoir that maintains infection when CD4+ T cell numbers

have declined to extremely low levels.

Some people are resistant to certain strains of HIV.[65]For example people with the

CCR5-32 mutation are resistant to infection with R5 virus as the mutation stops HIVfrom binding to this coreceptor, reducing its ability to infect target cells.

Sexual intercourse is the major mode of HIV transmission. Both X4 and R5 HIV are

present in the seminal fluid, which is passed from a male to his sexual partner. Thevirions can then infect numerous cellular targets and disseminate into the whole

organism. However, a selection process leads to a predominant transmission of the R5

virus through this pathway.[66][67][68] How this selective process works is still under

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investigation, but one model is that spermatozoamay selectively carry R5 HIV as they

possess both CCR3 and CCR5 but not CXCR4 on their surface[69]and that genital

epithelial cells preferentially sequester X4 virus.[70]In patients infected with subtype BHIV-1, there is often a co-receptor switch in late-stage disease and T-tropic variants

appear that can infect a variety of T cells through CXCR4.[71] These variants then

replicate more aggressively with heightened virulence that causes rapid T cell depletion,immune system collapse, and opportunistic infections that mark the advent of AIDS.[72]

Thus, during the course of infection, viral adaptation to the use of CXCR4 instead of

CCR5 may be a key step in the progression to AIDS. A number of studies with subtypeB-infected individuals have determined that between 40 and 50% of AIDS patients can

harbour viruses of the SI, and presumably the X4, phenotype.[73][74]

HIV-2 is much less pathogenic than HIV-1 and is restricted in its worldwide distribution.

The adoption of "accessory genes" by HIV-2 and its more promiscuous pattern ofcoreceptor usage (including CD4-independence) may assist the virus in its adaptation to

avoid innate restriction factors present in host cells. Adaptation to use normal cellular

machinery to enable transmission and productive infection has also aided theestablishment of HIV-2 replication in humans. A survival strategy for any infectiousagent is not to kill its host but ultimately become acommensalorganism. Having

achieved a low pathogenicity, over time, variants more successful at transmission will be

selected.[75]

Replication cycle

The HIV replication cycle

Entry to the cell

HIV enters macrophagesand CD4+T cells by the adsorption ofglycoproteins on itssurface to receptors on the target cell followed by fusion of theviral envelope with the

cell membrane and the release of the HIV capsid into the cell.[76][77]

Entry to the cell begins through interaction of the trimeric envelope complex (gp160

spike) and both CD4 and a chemokine receptor (generally eitherCCR5orCXCR4, butothers are known to interact) on the cell surface.[76][77] gp120 binds to integrin 47activating LFA-1 the central integrin involved in the establishment of virological

synapses, which facilitate efficient cell-to-cell spreading of HIV-1.[78]

The gp160 spikecontains binding domains for both CD4 and chemokine receptors.[76][77]

The first step in fusion involves the high-affinity attachment of the CD4 binding domains

ofgp120 to CD4. Once gp120 is bound with the CD4 protein, the envelope complex

undergoes a structural change, exposing the chemokine binding domains of gp120 andallowing them to interact with the target chemokine receptor.[76][77] This allows for a more

stable two-pronged attachment, which allows the N-terminal fusion peptide gp41 to

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penetrate the cell membrane.[76][77] Repeat sequences in gp41, HR1 and HR2 then interact,

causing the collapse of the extracellular portion of gp41 into a hairpin. This loop structure

brings the virus and cell membranes close together, allowing fusion of the membranesand subsequent entry of the viral capsid.[76][77]

After HIV has bound to the target cell, the HIV RNA and various enzymes, includingreverse transcriptase, integrase, ribonuclease, and protease, are injected into the cell.[76]

During the microtubule based transport to the nucleus, the viral single strand RNAgenome is transcribed into double strand DNA, which is then integrated into a host

chromosome.

HIV can infect dendritic cells (DCs) by this CD4-CCR5route, but another route using

mannose-specific C-type lectin receptors such as DC-SIGN can also be used.[79] DCs areone of the first cells encountered by the virus during sexual transmission. They are

currently thought to play an important role by transmitting HIV to T-cells when the virus

is captured in the mucosa by DCs.[79] The presence ofFEZ-1, which occurs naturally in

neurons, is believed to prevent the infection of cells by HIV.

[80]

Replication and transcription

Shortly after the viral capsid enters the cell, anenzyme calledreverse transcriptase

liberates the single-stranded (+)RNA genome from the attached viral proteins and copiesit into a complementary DNA (cDNA) molecule.[81]The process of reverse transcription

is extremely error-prone, and the resulting mutations may cause drug resistance or allow

the virus to evade the body's immune system. The reverse transcriptase also has

ribonuclease activity that degrades the viral RNA during the synthesis of cDNA, as wellas DNA-dependent DNA polymerase activity that creates a senseDNA from the

antisense cDNA.

[82]

Together, the cDNA and its complement form a double-stranded viralDNA that is then transported into the cell nucleus. The integration of the viral DNA intothe host cell's genome is carried out by another viral enzyme calledintegrase.[81]

Reverse transcription of the HIV genome into double strand DNA

This integrated viral DNA may then lie dormant, in the latent stage of HIV infection.[81]

To actively produce the virus, certain cellulartranscription factors need to be present, the

most important of which is NF- B (NF kappa B), which is upregulated when T-cells

become activated.

[83]

This means that those cells most likely to be killed by HIV are thosecurrently fighting infection.

During viral replication, the integrated DNA provirus is transcribedinto mRNA, which is

then spliced into smaller pieces. These small pieces are exported from the nucleus intothe cytoplasm, where they aretranslatedinto the regulatory proteinsTat (which

encourages new virus production) and Rev. As the newly produced Rev protein

accumulates in the nucleus, it binds to viral mRNAs and allows unspliced RNAs to leave

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retroviral DNA sequence that is a recombinant between the two parental genomes.[86] This

recombination is most obvious when it occurs between subtypes.[86]

The closely related simian immunodeficiency virus(SIV) has evolved into many strains,classified by the natural host species. SIV strains of the African green monkey(SIVagm)

andsooty mangabey (SIVsmm) are thought to have a long evolutionary history with theirhosts. These hosts have adapted to the presence of the virus,[89]which is present at high

levels in the host's blood but evokes only a mild immune response,[90] does not cause thedevelopment of simian AIDS,[91] and does not undergo the extensive mutation and

recombination typical of HIV infection in humans.[92]

In contrast, when these strains infect species that have not adapted to SIV ("heterologous"

hosts such as rhesus or cynomologus macaques), the animals develop AIDS and the virusgenerates genetic diversity similar to what is seen in human HIV infection.[93]

Chimpanzee SIV (SIVcpz), the closest genetic relative of HIV-1, is associated with

increased mortality and AIDS-like symptoms in its natural host.[94] Both SIVcpz and

HIV-1 appear to have been transmitted relatively recently to chimpanzee and humanpopulations, so their hosts have not yet adapted to the virus.[89] Both viruses have also lost

a function of the Nefgene that is present in most SIVs; without this function, T celldepletion is more likely, leading to immunodeficiency.[94]

Three groups of HIV-1 have been identified on the basis of differences in the envelope

(env) region: M, N, and O.[95] Group M is the most prevalent and is subdivided into eight

subtypes (orclades), based on the whole genome, which are geographically distinct.[96]

The most prevalent are subtypes B (found mainly in North America and Europe), A and

D (found mainly in Africa), and C (found mainly in Africa and Asia); these subtypes

form branches in the phylogenetic tree representing the lineage of the M group of HIV-1.

Coinfection with distinct subtypes gives rise to circulating recombinant forms (CRFs). In2000, the last year in which an analysis of global subtype prevalence was made, 47.2% of

infections worldwide were of subtype C, 26.7% were of subtype A/CRF02_AG, 12.3%

were of subtype B, 5.3% were of subtype D, 3.2% were of CRF_AE, and the remaining5.3% were composed of other subtypes and CRFs.[97] Most HIV-1 research is focused on

subtype B; few laboratories focus on the other subtypes.[98]The existence of a fourth

group, "P", has been hypothesised based on a virus isolated in 2009.[99][100][101] The strain isapparently derived from gorillaSIV (SIVgor), first isolated from western lowland gorillas

in 2006.[99]

The genetic sequence of HIV-2 is only partially homologous to HIV-1 and more closely

resembles that of SIVsmm.

Diagnosis

Main article: HIV test

Many HIV-positive people are unaware that they are infected with the virus.[102] For

example, less than 1% of the sexually active urban population in Africa have been tested

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and this proportion is even lower in rural populations.[102] Furthermore, only 0.5% of

pregnant womenattending urban health facilities are counselled, tested or receive their

test results.[102] Again, this proportion is even lower in rural health facilities.[102] Sincedonors may therefore be unaware of their infection, donor blood and blood products used

in medicine and medical research are routinely screened for HIV.[103]

HIV-1 testing consists of initial screening with an enzyme-linked immunosorbent assay

(ELISA) to detect antibodies to HIV-1. Specimens with a nonreactive result from theinitial ELISA are considered HIV-negative unless new exposure to an infected partner or

partner of unknown HIV status has occurred. Specimens with a reactive ELISA result are

retested in duplicate.[104] If the result of either duplicate test is reactive, the specimen isreported as repeatedly reactive and undergoes confirmatory testing with a more specific

supplemental test (e.g., Western blot or, less commonly, an immunofluorescence assay

(IFA)). Only specimens that are repeatedly reactive by ELISA and positive by IFA orreactive by Western blot are considered HIV-positive and indicative of HIV infection.

Specimens that are repeatedly ELISA-reactive occasionally provide an indeterminate

Western blot result, which may be either an incomplete antibody response to HIV in aninfected person, or nonspecific reactions in an uninfected person.[105]

Although IFA can be used to confirm infection in these ambiguous cases, this assay is not

widely used. Generally, a second specimen should be collected more than a month later

and retested for persons with indeterminate Western blot results. Although much lesscommonly available, nucleic acidtesting (e.g., viral RNA or proviral DNA amplification

method) can also help diagnosis in certain situations.[104] In addition, a few tested

specimens might provide inconclusive results because of a low quantity specimen. In

these situations, a second specimen is collected and tested for HIV infection.

Modern HIV testing is extremely accurate. The chance of a false-positive result in thetwo-step testing protocol is estimated to be 0.0004% to 0.0007% in the general U.S.

population.[106][107][108][109]

Treatment

Further information: Antiretroviral drugandPost-exposure prophylaxis

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Abacavir- a nucleoside analog reverse transcriptase inhibitors (NARTIs or NRTIs)

There is currently no publicly available vaccine or cure for HIV or AIDS.[110][111]

However, a vaccine that is a combination of two previously unsuccessful vaccine

candidates was reported in September 2009 to have resulted in a 30% reduction ininfections in a trial conducted in Thailand.[112] Additionally, a course of antiretroviral

treatment administered immediately after exposure, referred to as post-exposureprophylaxis, is believed to reduce the risk of infection if begun as quickly as possible.[113]

In July 2010, a vaginal gel containing tenofovir, a reverse transcriptase inhibitor, was

shown to reduce HIV infection rates by 39 percent in a trial conducted in South Africa.[114]

However, due to the incomplete protection provided by the vaccine and/or post-exposure

prophylaxis, the avoidance of exposure to the virus is expected to remain the only reliable

way to escape infection for some time yet. Current treatment for HIV infection consists

ofhighly active antiretroviral therapy, or HAART.

[115]

This has been highly beneficial tomany HIV-infected individuals since its introduction in 1996, when the protease

inhibitor-based HAART initially became available.[116]Current HAART options arecombinations (or "cocktails") consisting of at least three drugs belonging to at least two

types, or "classes," ofantiretroviral agents. Typically, these classes are two nucleoside

analogue reverse transcriptase inhibitors (NARTIs or NRTIs) plus either a proteaseinhibitoror a non-nucleoside reverse transcriptase inhibitor(NNRTI).

There is no empirical evidence for withholding treatment at any stage of HIV infection,[117] and death rates are almost twice as high when therapy is deferred (until the CD4

count falls below 500) compared to starting therapy when the CD4 count is above 500.[29]

However, the timing for starting HIV treatment is still subject to debate.

[118]

The United States Panel on Antiretroviral Guidelines for Adults and Adolescents in 2009

recommended that antiretroviral therapy should be initiated in all patients with a CD4

count less than 350, with treatment also recommended for patients with CD4 countsbetween 350 and 500. However for patients with CD4 counts over 500, the expert Panel

was evenly divided, with 50% in favor of starting antiretroviral therapy at this stage of

HIV disease, and 50% viewing initiating therapy at this stage as optional. They noted that"Patients initiating antiretroviral therapy should be willing and able to commit to lifelong

treatment and should understand the benefits and risks of therapy and the importance of

adherence".[119]

New classes of drugs such asentry inhibitorsprovide treatment options for patients whoare infected with viruses already resistant to common therapies, although they are not

widely available and not typically accessible in resource-limited settings. Because AIDS

progression in children is more rapid and less predictable than in adults, particularly in

young infants, more aggressive treatment is recommended for children than adults.[120] Indeveloped countries where HAART is available, doctors assess their patients thoroughly:

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measuring the viral load, how fast CD4 declines, and patient readiness. They then decide

when to recommend starting treatment.[121]

HAART neither cures the patient nor does it uniformly remove all symptoms; high levelsof HIV-1, often HAART resistant, return if treatment is stopped.[122][123] Moreover, it

would take more than a lifetime for HIV infection to be cleared using HAART.[124]

Despite this, many HIV-infected individuals have experienced remarkable improvements

in their general health and quality of life, which has led to a large reduction in HIV-associated morbidity and mortality in the developed world.[116][125][126] One study suggests

the average life expectancy of an HIV infected individual is 32 years from the time of

infection if treatment is started when the CD4 count is 350/L. [127] Life expectancy isfurther enhanced ifantiretroviral therapy is initiated before the CD4 count falls below

500/L.[29]

In the absence of HAART, progression from HIV infection to AIDS has been observed to

occur at a median of between nine to ten years and the median survival time after

developing AIDS is only 9.2 months.

[15]

However, HAART sometimes achieves far lessthan optimal results, in some circumstances being effective in less than fifty percent of

patients. This is due to a variety of reasons such as medication intolerance/side effects,prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV.

However, non-adherence and non-persistence with antiretroviral therapy is the major

reason most individuals fail to benefit from HAART.[128]

The reasons for non-adherence and non-persistence with HAART are varied andoverlapping. Major psychosocial issues, such as poor access to medical care, inadequate

social supports, psychiatric disease and drug abuse contribute to non-adherence. The

complexity of these HAART regimens, whether due to pill number, dosing frequency,

meal restrictions or other issues along with side effectsthat create intentional non-adherence also contribute to this problem.[129][130][131] The side effects include

lipodystrophy, dyslipidemia, insulin resistance, an increase incardiovascularrisks, and

birth defects.[132][133]

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.[134] Research to

improve current treatments includes decreasing side effects of current drugs, furthersimplifying drug regimens to improve adherence, and determining the best sequence of

regimens to manage drug resistance. Unfortunately, only a vaccine is thought to be able

to halt the pandemic. This is because a vaccine would cost less, thus being affordable for

developing countries, and would not require daily treatment.[134]However, after over 20years of research, HIV-1 remains a difficult target for a vaccine.[134]

Treatments in development

There is an anecdotal case of an HIV-positive patient who had bothacute myelogenous

leukemia (AML) and HIV infection, was said by some to be "functionally cured" of his

HIV following a bone marrow transplantfor AML. The bone marrow donor had been

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elogenous_leukemiahttp://en.wikipedia.org/wiki/Acute_myelogenous_leukemiahttp://en.wikipedia.org/wiki/Bone_marrow_transplant

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selected as homozygous for a CCR5-32 mutation (which confers resistance to "almost

all strains of HIV").[135][136] After 600 days without antiretroviral drug treatment, HIV

levels in the person's blood, bone marrow and bowel were below the limit of detection,although the authors note that the virus is likely present in other tissues. Researchers

cautioned that it would be premature to consider this treatment a possible cure because of

its anecdotal nature, the mortality risk associated with bone marrow transplants and otherconcerns.[137][138]

In 2010, a chemical called BanLec was reported to be a potentinhibitor of HIV

replication.[139][140] Researchers found that BanLec bound to the HIV-1envelope protein

gp120, which is high in sugar content, inhibiting viral entry into human cells.[139][140] Theresearchers suggest that such an inhibitor of HIV infection may find use as a topical

treatment, such as avaginalmicrobicide, and may be cheaper to produce than current

antiviral topical treatments.[141] BanLec is not FDA approved for the treatment of HIV-1infection and it should not be used to treat or prevent HIV-1 infection.

A combination ofpeptides that stimulate integration together with the protease inhibitorRo 31-8959 cause apoptotic cell death ofcultured cells that were infected with HIV

without apparent damage to uninfected cells.[142]No animal or human tests of thiscombination have been reported.[143]

HIV latent reservoir

Despite the success of highly active antiretroviral therapy (HAART) in controlling HIV

infection and reducing HIV-associated mortality, current drug regimens are unable to

completely eradicate HIV infection. Many people on HAART achieve suppression ofHIV to levels below the limit of detection of standard clinical assays for many years.

However, upon withdrawal of HAART, HIV viral loads rebound quickly with aconcomitant decline in CD4+T-Cells, which, in most cases, absent a resumption of

treatment, leads to AIDS.

To successfully reproduce itself, HIV must convert its RNA genometoDNA, which is

then imported into the host cell's nucleus and inserted into the host genome through the

action ofHIV integrase. Because HIV's primary cellular target, CD4+ T-Cells, function

as the memory cells of the immune system, integrated HIV can remain dormantfor theduration of these cell's lifetime. Memory T-Cells may survive for many years and

possibly for decades. The latent HIV reservoir can be measured by co-culturing CD4+ T-

Cells from infected patients with CD4+ T-Cells from uninfected donors and measuring

HIV protein or RNA.

[144]

The failure of vaccine candidates to protect against HIV infection and progression to

AIDS has led to a renewed focus on the biological mechanisms responsible for HIV

latency. A limited period of therapy combining anti-retrovirals with drugs targeting thelatent reservoir may one day allow for total eradication of HIV infection.[145]

Prognosis

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Without treatment, the net median survival time after infection with HIV is estimated to

be 9 to 11 years, depending on the HIV subtype,[146] and the median survival rate after

diagnosis of AIDS in resource-limited settings where treatment is not available rangesbetween 6 and 19 months, depending on the study.[147] In areas where it is widely

available, the development ofHAARTas effective therapy for HIV infection and AIDS

reduced the death rate from this disease by 80%, and raised the life expectancy for anewly diagnosed HIV-infected person to 2050 years.[148][149]

As new treatments continue to be developed and because HIV continues toevolve

resistance to treatments, estimates of survival time are likely to continue to change.

Without antiretroviral therapy, death normally occurs within a year after the individualprogresses to AIDS.[15] Most patients die from opportunistic infections ormalignancies

associated with the progressive failure of the immune system.[11] The rate of clinical

disease progression varies widely between individuals and has been shown to be affectedby many factors such as host susceptibility and immune function[65][150][151] health care and

co-infections,[11][15] as well as which particular strain of the virus is involved.[152][153][154]

Epidemiology

Main article: AIDS pandemic

Numbers of people living with, newly infected with, and killed by HIV (1990-2008)[155]

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

Disability-adjusted life yearfor HIV and AIDS per 100,000 inhabitants.no data 10 10-25 25-50 50-100 100-500 500-1000 1000-2500 2500-50005000-7500 7500-10000 10000-50000 50000

UNAIDS and the WHO estimate that AIDS has killed more than 25 million people since

it was first recognized in 1981, making it one of the most destructive pandemics inrecorded history. Despite recent improved access to antiretroviral treatment and care in

many regions of the world, the AIDS pandemic claimed an estimated 2.8 million

(between 2.4 and 3.3 million) lives in 2005 of which more than half a million (570,000)

were children.[5]

In 2007, between 30.6 and 36.1 million people were believed to live with HIV, and it

killed an estimated 2.1 million people that year, including 330,000 children; there were

2.5 million new infections.[146]

Sub-Saharan Africa remains by far the worst-affected region, with an estimated 21.6 to27.4 million people currently living with HIV. Two million (1.53.0 million) of them are

children younger than 15 years of age. More than 64% of all people living with HIV are

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in sub-Saharan Africa, as are more than three quarters of all women living with HIV. In

2005, there were 12.0 million (10.613.6 million)AIDS orphans living in sub-Saharan

Africa 2005.[5]

South & South East Asia are second-worst affected with 15% of the total. AIDS accounts

for the deaths of 500,000 children in this region. South Africa has the largest number ofHIV patients in the world followed by Nigeria.[156] Other Sub-Saharan countries, such as

the Sudan report lower prevalences of 1.6%, although the data is poorly documented.[157]

India has an estimated 2.5 million infections (0.23% of population), making India the

country with the third largest population of HIV patients. In the 35 African nations with

the highest prevalence, averagelife expectancy is 48.3 years6.5 years less than itwould be without the disease.[158]

The latest evaluation report of the World Bank's Operations Evaluation Department

assesses the development effectiveness of the World Bank's country-level HIV/AIDS

assistance defined as policy dialogue, analytic work, and lending with the explicit

objective of reducing the scope or impact of the AIDS epidemic.

[159]

This is the firstcomprehensive evaluation of the World Bank's HIV/AIDS support to countries, from the

beginning of the epidemic through mid-2004. Because the Bank aims to assist inimplementation of national government programmes, their experience provides important

insights on how national AIDS programmes can be made more effective.

The development ofHAART as effective therapy for HIV infection has substantially

reduced the death rate from this disease in those areas where these drugs are widelyavailable.[116] As the life expectancy of persons with HIV has increased in countries where

HAART is widely used, the continuing spread of the disease has caused the number of

persons living with HIV to increase substantially.

In Africa, the number of mother-to-child-transmission (MTCT) cases and the prevalenceof AIDS is beginning to reverse decades of steady progress in child survival. Countries

such as Uganda are attempting to curb the MTCT epidemic by offering VCT (voluntary

counselling and testing), PMTCT (prevention of mother-to-child transmission) and ANC(ante-natal care) services, which include the distribution of antiretroviral therapy.

History

Origins

Main article: Origin of AIDSSee History of known cases and spreadfor early cases of HIV / AIDS

HIV is thought to have originated in non-human primates in sub-Saharan Africa and wastransferred to humans late in the 19th or early in the 20th century.[160] The first paper

recognizing a pattern of opportunistic infections characteristic of AIDS was published in

1981.[161]

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zur Hausenalso shared the Prize for his discovery that human papilloma virus leads to

cervical cancer, but Gallo was left out.[176]Gallo said that it was "a disappointment" that

he was not named a co-recipient.[177] Montagnier said he was "surprised" Gallo was notrecognized by the Nobel Committee: "It was important to prove that HIV was the cause

of AIDS, and Gallo had a very important role in that. I'm very sorry for Robert Gallo." [176]

AIDS denialism

Main article: AIDS denialism

A small group of individuals continue to dispute the connection between HIV and AIDS,[178] the existence of HIV itself, or the validity of HIV testing and treatment methods.[179]

[180] These claims, known as AIDS denialism, have been examined and rejected by the

scientific community.[181] However, they have had a significant political impact,particularly in South Africa, where the government's official embrace of AIDS denialism

was responsible for its ineffective response to that country's AIDS epidemic, and has

been blamed for hundreds of thousands of avoidable deaths and HIV infections.[182][183][184]

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