PRIMARY HIV-1 INFECTION: DIAGNOSIS AND TREATMENT

Author
Paul E Sax, MD
Section Editor
John G Bartlett, MD
Deputy Editor
Barbara H McGovern, MD
Disclosures
Literature review current through: May 2012. |This topic last updated: jun 14, 2011.
INTRODUCTION Primary HIV-1 infection may present as a mononucleosis type of syndrome
with a constellation of nonspecific symptoms. Without a high index of suspicion, the diagnosis can
frequently be missed by well-intentioned physicians.
The diagnosis and treatment of primary HIV will be reviewed here. The pathogenesis, epidemiology,
and clinical manifestations of this infection are discussed separately. (See "Primary HIV-1 infection:
Pathogenesis; epidemiology and clinical manifestations".)
PUBLIC HEALTH IMPLICATIONS Establishing the diagnosis of primary HIV infection is clearly
important from the public health perspective. Patients are typically highly infectious during acute
HIV due to an enormous viral burden in blood and genital secretions [1]. Such patients may be
unaware that they are infected and continue to engage in risky sexual activity and needle sharing,
putting others at risk. Pregnant women who are unaware of their acute infection can transmit HIV
perinatally unless a timely diagnosis is made and antiretroviral therapy is initiated [2].
Mathematical models suggest that a large proportion of all HIV infections may be transmitted by
individuals with primary infection [3,4]. This was illustrated in a retrospective study of 235
monogamous, HIV-discordant couples in Uganda. HIV transmission was confirmed by viral
sequence analysis in 68 patients [5]. The highest rates of acquisition were among partners of
patients who recently acquired HIV followed by those with end-stage AIDS. The period of greatest
risk is in the earliest stages of acute HIV, during which there is a very high viral load and no
detectable antibody [4].
ESTABLISHING THE DIAGNOSIS The diagnosis of acute HIV infection is infrequently made in
clinical practice. In a case series from Seattle, for example, the diagnosis of HIV infection was
considered in only 5 of 19 patients (26 percent) who sought care from their primary care physicians,
emergency departments, and walk-in clinics [6]. This finding was especially surprising since these
patients were enrolled in a surveillance program for HIV.
There are several reasons why acute HIV infection is so infrequently diagnosed:

The symptoms especially in mild cases are nonspecific and resolve

spontaneously without treatment [7].

Clinicians may be uncomfortable asking questions about sexual exposure or

intravenous drug-use, especially with patients whom they see infrequently, such as
young, previously healthy individuals.

Primary care physicians may not be aware of high-risk behavior even in patients they
know well. Such patients often choose to undergo counseling and serial serologic
testing at an anonymous clinic rather than to discuss risk behaviors with their primary
care provider.

Patients may not perceive themselves to be at risk. We have seen several men who
acquired HIV through receptive oral sex and expressed surprise that this was a mode
of HIV transmission.

Given the importance of establishing the diagnosis of acute HIV infection both for the individual and
for its public health implications, we propose the following approach to the patient who presents
with an ill-defined febrile illness, heterophile-negative mononucleosis-like syndrome, and/or aseptic
meningitis:

Question all patients about HIV risk behaviors including sexual activity and injection
drug use.

Perform a thorough physical examination with particular attention to the signs of

primary HIV infection such as rash, mucocutaneous ulcers, and lymphadenopathy.

Perform a HIV antibody test. This serves two important purposes: it establishes
whether chronic HIV infection is present, and it initiates a discussion about the
implications of HIV testing with the patient since most states require informed consent
for HIV antibody testing.

Obtain an HIV viral load test.

The diagnosis of acute HIV infection is established by demonstrating a high viral load or a positive
p24 antigen in a patient with typical clinical features and a negative or indeterminate HIV serologic
test. Biopsy of a skin lesion usually does not assist in the diagnosis of primary HIV infection due to
the nonspecific nature of the histopathologic changes.
As an alternative to the above two-test strategy, another option is a combined HIV antibody/p24
antigen assay, approved by the FDA in 2010 [8,9]. Point of care tests that simultaneously detect
HIV antibody and antigen are also under development.
Viral load Patients with acute HIV have a markedly elevated viral load, easily detectable with
viral load tests. In one study, for example, all patients with acute HIV had values >100,000
copies/mL [10]. An additional finding in this study was the occurrence of false-positive viral loads in
8 of 303 (2.6 percent) patients without HIV infection.

Importantly, all of the false-positives had <2000 copies/mL, making them easily distinguishable from
the true positives whose values were much higher. Furthermore, all of the false positives occurred
with the bDNA rather than RT-PCR version of the test.
As a result, the preferred viral load test for diagnosis of acute HIV infection is RT-PCR. A false
positive test should be suspected if the viral load is low (<10,000 copies/mL) in the setting of
suspected acute HIV infection [11,12]. A repeat sample should be drawn in this setting since a
rising viral load suggests a true positive result.
Nucleic acid amplification testing (NAT) is a sensitive method to detect acute HIV viremia in patients
who are antibody-negative. However, NAT is an expensive test to utilize as a screening tool for the
detection of acute HIV infection in large populations. Interest in the use of pooled specimen testing
to decrease the cost of the assay has increased due to the ability of NAT to detect HIV RNA at
levels of 75 copies/microL or lower. False positive NAT test results occur in three to five percent of
patients, depending on the population prevalence [13]. If the HIV RNA level is less than 2000
copies/mL, risk reduction behavior coupled with repeat testing should be offered, since a rising level
of HIV RNA is consistent with true infection [14].
The addition of pooled specimen NAT to standard HIV antibody testing was evaluated for the
detection of acute HIV in 109,250 persons at risk in North Carolina [15]. Chronic HIV infection was
diagnosed in 583 patients by standard ELISA and Western blot assays; of these, 107 infections
were recently acquired as identified by detuned ELISA testing. Use of NAT on 108,667 samples
with negative or indeterminate results on standard antibody assays detected an additional 25
subjects with viremia. Acute HIV infection was confirmed in 23 patients. (See 'Serologic studies'
below.)
A p24 antigen assay is a less costly but also less sensitive alternative to viral load testing, and in
one series was falsely negative in 5 out of 54 patients with acute HIV [10,16]. (See "Techniques and
interpretation of HIV-1 RNA quantitation".)
Serologic studies Primary HIV infection is ultimately confirmed serologically by the appearance
of antibodies to HIV. (See "Diagnostic assays for HIV infection".) In one study of eight patients with
symptomatic primary HIV infection, IgM antibody by immunofluorescence assay (IFA) was detected
at a mean of 53 days and IgG antibodies at a mean of 113 days after the onset of symptoms [17].
However, the standard third generation enzyme linked immunosorbent assays (ELISAs) used in
clinical practice and in blood banks in the United States do not detect antibodies to HIV until three
to seven weeks after infection.
Very early treatment for primary HIV infection has rarely led to abrogation of HIV antibody
responses [18,19]. In a cohort of 150 patients with symptomatic primary HIV infection that was
treated with antiretroviral therapy, three patients did not develop a fully evolved antibody response
and/or demonstrate evidence of seroreversion after successful HIV RNA suppression. In another
study of 75 acutely infected patients who had positive EIA antibody results at the time of initiation of

ART, five subsequently developed a negative result on at least one second generation EIA test [19].
It has been postulated that maturation of the humoral response was thwarted by rapid HIV RNA
suppression early in the course of disease [20]. It is critical that physicians and patients understand
that the rare event of seroreversion does not indicate viral eradication [19,21].
"Detuned ELISA"/STARHS The Serologic Testing Algorithm for Recent HIV Seroconversion
(STARHS or "detuned ELISA") is available from some research laboratories and the CDC to
establish whether patients with positive HIV antibody tests have recently-acquired HIV [22]. Since
such patients have HIV antibody levels that are still rising, a positive test on a currently available
(and highly sensitive) HIV ELISA at the same time a less-sensitive ELISA is negative provides
strong evidence that the patient has recently seroconverted, and that HIV acquisition has occurred
within the previous 170 days. The use of the less-sensitive ELISA has been helpful in defining HIV
incidence among groups of patients who already have a positive HIV antibody test [15,23].
Use of the detuned ELISA may aid public health interventions by highlighting important
demographic information regarding recently infected populations. In one study, based in Australia
during a period of rising numbers of HIV diagnoses, the use of the detuned ELISA identified 132
incident infections from 317 specimens identified through surveillance [24]. Of note, it also
misclassified 13 specimens in patients who had laboratory markers of advanced disease. This test
is not currently available from commercial laboratories.
Genotype resistance testing HIV strains resistant to currently available antiretroviral drugs may
be transmitted [25]. These strains are strongly influenced by antiretroviral drug use patterns in the
source. (See "Primary HIV-1 infection: Pathogenesis; epidemiology and clinical manifestations".)
As a result, it is recommended that all patients with documented primary HIV infection also undergo
resistance testing after the diagnosis has been established, regardless of whether treatment is
being considered [26,27]. Determination of the patient's drug resistance profile is important since
some resistance mutations may become undetectable over time without the selection pressure of
antiretroviral therapy. Selection of treatment regimens in the future should consider these initially
detected resistance mutations, as their presence may reduce the response to certain antiviral
agents. One study of 107 patients with acute HIV infection demonstrated that minority variants
(including viruses harboring the M184V mutation) were efficiently suppressed in patients who
received a ritonavir-boosted PI and two NRTIs [28].
While both genotype and phenotype testing are available, genotype testing is preferred since the
procedure is more standardized, the cost of the test is lower, and the turnaround time is faster
(approximately one to two versus three to four weeks). In addition, genotype testing is more
sensitive for mixtures of resistant and wild-type virus. (See "Overview of HIV drug resistance testing
assays".)
In the absence of antiretroviral therapy, drug resistance tests are generally able to detect resistance
longer in patients who are initially infected with a drug-resistant strain of HIV (primary drug

resistance) than in patients who develop secondary drug resistance. (See "Drug resistance testing
in the clinical management of HIV infection".)
Prevention counseling All patients with suspected or confirmed acute HIV infection should be
counseled to adopt behaviors that guard against HIV transmission, including consistent and correct
condom use and avoidance of sharing injection drug use equipment. There is a particularly high risk
of transmission during primary HIV infection, when virus loads are often exceedingly high (100,000
to one million copies/mL compared to an average viral burden without therapy of 30,000 to 50,000
copies/mL in chronic infection) [29,30].
All patients with newly diagnosed HIV infection should also undergo testing for other sexually
transmitted diseases as recommended by the Centers for Disease Control and Prevention. (See
"Prevention of sexually transmitted diseases".)
RATIONALE FOR TREATMENT
Potential benefits The debate about aggressive antiretroviral treatment of primary HIV infection
continues [27,31]. Preliminary data suggest that treatment of acute HIV infection may result in
preservation of HIV-specific cellular immune function and establishment of a lower viral set point
after HIV therapy is stopped. Additionally, antiretroviral therapy may lead to decreased B cell
activation, reduction of apoptosis, and restoration of memory B cell pools [32]. However, not all
studies have suggested such a benefit on viral set point [33]. Further potential advantages of early
intervention include:

Reduced risk of viral transmission

Decreased severity of the symptoms of the acute infection

Limitation of viral mutation, including the evolution of drug resistance

Maturation and preservation of HIV-specific immune responses [34,35]

Earlier decay of cellular reservoirs [36,37]

Prolongation of the total time patients can remain off chronic therapy [38]

Potential risks The theoretic benefits of early treatment must be balanced against the possible
risks, including:

Higher risk of long-term drug toxicities due to a longer duration of antiretroviral

exposure [39]

Evolution of drug resistance if therapy fails to completely suppress viral replication

Given the increased safety of current treatments, concerns about drug toxicity are less relevant
compared with earlier days of ART. In addition, the CD4 cell threshold for initiation of ART is 500
cells/mm3, which is markedly higher than the previous threshold of 350 cells/mm3, and many
patients meet this threshold relatively soon after diagnosis [40]. One study of acute HIV
seroconverters found the probability of having a rst CD4 cell count below 500 cells/mm3 after

seroconversion was 0.57, 0.72, 0.79 and 0.84 at baseline, and two, four, and six years after the
initial diagnosis [41]. As a result, patients with acute HIV who start therapy at the time of diagnosis
would not be adding a significant amount of drug exposure since they would be highly likely to meet
the CD4 threshold of 500 cells/mm3 within a few years of initial infection.
Prevention of drug resistance requires patient commitment to strict adherence if treatment is
initiated during acute infection when the rate of viral replication is particularly rapid. As noted above,
acquisition of a drug-resistant strain of virus is also a possibility, and a resistance test should be
done after the diagnosis of acute HIV is confirmed.
CLINICAL STUDIES Since acute HIV infection is seldom recognized in clinical practice, data
about outcomes of early antiretroviral therapy are limited. Thus, it is currently unknown whether
treatment of acute HIV infection results in long-term virologic, immunologic, or clinical benefit. The
Department of Health and Human Services (DHHS) has suggested that treatment of primary HIV
infection should be considered optional [27]; by contrast, the International AIDS Society-USA has
recommended treatment for individuals with acute symptomatic HIV [40].
United States A prospective longitudinal analysis of clinical markers in 102 patients with primary
HIV infection was performed to assess the risks and benefits of early treatment intervention [42].
Patients were divided into two groups on the basis of the phase of HIV infection at the time of
initiation of treatment. Preseroconversion was defined by the presence of HIV-1 RNA and negative
results of HIV-1 antibody testing. Postseroconversion status was defined by positive results of HIV1 antibody testing with evidence of seroconversion occurring within the previous 12 months.
Fourteen patients who subsequently underwent a structured treatment interruption were excluded
from analysis. The study was significant for the following observations:

41 patients (40 percent) were treated during the preseroconversion phase and 55 (54
percent) had already experienced seroconversion.

The mean nadir CD4 count of 422 cells/microL increased to a mean of 702
cells/microL at 12 months and there was a continued incremental increase in CD4
counts over 60 months for subjects who remained on therapy. Ninety-seven percent of
patients also achieved virologic suppression, which was durable in the vast majority at
18 months of follow-up.

There was no significant difference in absolute CD4 counts or time to virologic

suppression for the pre- and postseroconversion groups.

Time to viral suppression was similar regardless of treatment regimen. Fifty-two

percent of patients discontinued at least one drug from their initial antiretroviral
regimen secondary to side effects.

This nonrandomized study is not designed to answer the question as to whether early therapy
should be the standard of care for primary HIV infection; however it does provide some data
regarding clinical expectations of the risks and benefits of treatment.

Duke-UNC Acute HIV Infection Consortium In a prospective, single arm study, 61 patients
with acute HIV infection were enrolled and treated with emtricitabine/tenofovir/efavirenz [43]. Of the
51 patients who had 48 weeks of follow-up, 41 (85 percent) achieved viral suppression to <50
copies/mL. Four patients had to undergo medication changes due to documented resistance to
efavirenz on genotypic testing and two discontinued medications because of side effects. Acutely
infected patients achieved viral suppression more rapidly than chronically infected participants from
a historical control group after adjustment for baseline viremia and CD4 cell counts.
AIDS Clinical Trial Group (ACTG) 371 ACTG 371 prospectively enrolled 121 patients with
acute or early HIV infection within 15 sites in the United States to assess the potential benefit of
early treatment [44]. All patients underwent treatment discontinuation after attaining a
nondetectable viral load for 52 weeks. Forty percent of the study patients sustained a viral load of
less than 5000 cells/microL after stopping treatment for 24 weeks; control of viremia did not differ
between patients with acute or early infection.
Acute Infection and Early Disease Research Program In the Acute Infection and Early
Disease Research Program, 337 patients were enrolled within six months of HIV seroconversion
and self-selected initiation of ART (for a minimum of 12 weeks) or deferral of treatment [34]. Of
these study participants, 58 chose to receive ART for either acute infection (n = 13 with
seroconversion within two weeks) or early infection (n = 45 with seroconversion within six months)
with the following results:

Initiation of ART within two weeks of seroconversion was associated with viral load
and CD4+ T-cell count benefits for up to 72 weeks after discontinuation of treatment
compared to patients who deferred therapy.

Patients who initiated ART later, but within six months of seroconversion, had lower
HIV RNA levels at 24 weeks than the untreated group; however, these differences
were no longer apparent by week 48.

Reasons for discontinuation of therapy or adverse events were not reported.

PRIMO and SEROCO cohorts PRIMO is an ongoing study, initiated in 1996, of 170 French
patients with acute HIV infection who started ART within three months after diagnosis, attained viral
suppression on treatment, and then interrupted ART for a minimum of three months [45]. The
French Seroconverters (SEROCO) cohort enrolled 1551 HIV-infected patients beginning in 1988.
The kinetics of CD4 cell decline were compared in 170 patients who received ART within the
PRIMO cohort and 123 never-treated patients within the SEROCO cohort. After ART interruption in
the PRIMO cohort, the CD4 cell count fell rapidly during the first five months and more slowly
thereafter; a larger increase in CD4 during treatment was associated with a larger and steeper
decline in CD4 after cessation of ART. By contrast, the CD4 decline in the SEROCO cohort was
less steep. As a result, the mean CD4 cell counts were similar (416 cells/microL) three years after
ART interruption (PRIMO) or after infection (SEROCO).

CASCADE cohort The Concerted Action on SeroConversion to AIDS and Death in Europe
(CASCADE) collaboration represents 23 cohorts in Europe, Australia, and Canada of individuals
with well-defined dates of seroconversion. One subset analysis of this cohort has compared
changes in CD4 cell counts and HIV RNA and clinical disease rates between 675 patients who
initiated combination therapy within the first six months after seroconversion ("early group") versus
348 patients who started treatment more than six months after seroconversion ("deferred treatment
group") [46]. Transient early therapy did not have an effect on viral load set point and had limited
beneficial effect on CD4 cell counts compared to those receiving deferred therapy.
Further clarification of the role of early intervention in acute HIV infection will await the results of an
ongoing trial, which compares no intervention with treatment given for three or 12 months [47].
PATIENT MANAGEMENT After a diagnosis of acute HIV infection is made, patients should
ideally be referred to an HIV specialist for management. Given that antiretroviral therapy for acute
infection remains controversial, enrollment in a research study is encouraged to provide more
information for clinicians about the outcome of early intervention [48]. Listings of available trials can
be found at www.clinicaltrials.gov. If referral to an HIV specialist or enrollment in a protocol is not
feasible, treatment should be initiated following the latest consensus guidelines on antiretroviral
therapy.
If a decision is made to treat a patient with acute HIV infection, the US Department of Health and
Human Services (DHHS) guidelines suggest selection of the same potent regimens recommended
for chronic HIV infection [27]. Regimens recommended by DHHS [27] and by the International AIDS
Society-USA Panel [49] are discussed separately. (See "Selecting antiretroviral regimens for the
treatment naive HIV-infected patient", section on 'Selecting a regimen'.)
It is particularly important that all medications in the antiretroviral regimen are started
simultaneously to minimize the development of drug resistance during this period of rapid viral
replication [50]. Prior to treatment, drug resistance testing should be performed to determine if
transmitted virus was resistant to any one antiretroviral medication; however, treatment should not
be delayed while awaiting results of genotypic testing in the setting of acute HIV infection. Once the
results are available, treatment modifications can be made accordingly. Since drug resistance to
nonnucleoside reverse transcriptase inhibitors (NNRTIs) is more common than with protease
inhibitors (PIs), a PI-based combination regimen is advised [27].
DURATION OF TREATMENT Once treatment is initiated, ART is continued indefinitely.
However, there have been case reports of patients treated during acute infection who were able to
come off of therapy and maintain the viral load at a relatively low level. It was proposed that
immunologic control may be related to virus-specific CD4 responses, which are lacking in most
patients with chronic infection, even when an undetectable viral load and a relatively normal
quantitative CD4 cell count are achieved. One of the goals of early treatment is to stimulate these
critical HIV-specific CD4 responses.

An early report described eight patients treated with combination antiretroviral therapy within 72
hours of the diagnosis, five of whom achieved virologic control after either a first or second
treatment interruption for a median of 6.5 months off of therapy [51]. Treatment of acute HIV in
these patients led to a vigorous, HIV-specific CD4 response similar to that seen in long-term
nonprogressors; the purpose of the treatment interruptions was to boost HIV immunity through
reexposure to HIV antigens.
However, formal testing of this proof-of-concept in larger trials has been thwarted by difficulty
identifying patients with acute HIV infection; furthermore, the results of one small multicenter study
(PRIMSTOP) were not as encouraging as the above case report. This multicenter, prospective trial
formally evaluated structured treatment interruptions in 29 patients with early symptomatic primary
HIV infection [52]. A 34-week treatment phase was followed by three consecutive periods of two,
four, and eight weeks off ART, each separated by 12 weeks on ART. Treatment was permanently
stopped at week 84 and patients were followed up for 24 weeks for assessment of virologic
success. Six months after discontinuation of therapy, only one patient had a non-detectable plasma
viral load; six patients had a viral load <1000 copies/microL, and three patients developed a major
mutation to protease inhibitors (L90M). These data suggest that the vast majority of patients who
initiate HIV therapy in the setting of acute infection fail to suppress viremia.
At this time, patients with primary HIV should be enrolled in clinical trials since the benefits of early
treatment are still unclear. If such a referral is not possible, we recommend discussing the risks and
benefits of treatment with the patient. Some patients will have no strong preference, and will ask for
guidance on this issue. Given the overall trend towards earlier initiation of antiretroviral therapy in
treatment-nave patients [40] and the strong evidence that treatment reduces the risk of HIV
transmission to others [40], we favor initiation of therapy if patients are willing to commit to lifelong
therapy.
COMPLICATIONS OF TRANSIENT IMMUNOSUPPRESSION Although usually associated with
later stage HIV disease, opportunistic infections can occur during the transient CD4 lymphopenia of
primary HIV [53]. Oral and esophageal candidiasis is the opportunistic infection most often seen in
these patients [54,55]. The factors responsible for the frequency of esophageal candidiasis during
the immunosuppression of acute HIV infection are not well understood [56]. Two possibilities are
that esophageal ulceration provides a local environment that promotes the growth of Candida
species, and that the administration of antibacterial antibiotics to empirically treat primary HIV may
alter normal oropharyngeal flora
Case reports of other opportunistic infections seen during acute HIV infection include:

One case of CMV proctitis in a young man with rectal pain and bleeding in association
with more typical features of the acute retroviral syndrome [57]. Colonoscopy showed
diffuse edema, erythema, and friability of the rectal mucosa; biopsy revealed
characteristic inclusion bodies in the vascular endothelium and lamina propria. The

proctitis symptoms spontaneously improved within several weeks; repeat rectal biopsy
confirmed resolution of CMV.

Three patients with Pneumocystis carinii pneumonia 8 to 14 days after initial

presentation with primary HIV infection [58]; CD4 counts were very low (63 to
91/microL) in these patients.

One case of severe and prolonged cryptosporidiosis complicating acute HIV infection
[59].

Several patients have acquired thrush.

RECURRENT SYMPTOMATIC ACUTE HIV Several case reports have described a clinical
syndrome resembling primary HIV in patients with chronic HIV infection who discontinued effective
antiretroviral therapy [60,61]. Symptoms including fever, lymphadenopathy, and rash developed in
four patients ten days to four weeks after discontinuing all antiretroviral drugs. Viral loads which had
been <50 copies/mL in all of the patients rose dramatically to as high as 1,000,000 copies/mL and
CD4 counts dropped appreciably. Resumption of therapy produced resolution of symptoms,
decrease in viral load, and increase in CD4 counts. Cases of recrudescent symptomatic acute HIV
have also been reported in patients treated during acute infection who have stopped treatment [62].
SUMMARY AND RECOMMENDATIONS

Primary HIV-1 infection may present as a mononucleosis-like syndrome with a

constellation of nonspecific symptoms. Without a high index of suspicion, the
diagnosis can frequently be missed. (See 'Introduction' above.)

Patients who present with an ill-defined febrile illness, heterophile-negative

mononucleosis-like syndrome, and/or aseptic meningitis should be assessed for risktaking behaviors, such as engaging in unprotected sex or injection drug use.
Diagnostic testing for HIV infection should include an HIV antibody and HIV RNA
testing. (See 'Establishing the diagnosis' above.)

Patients with acute HIV infection usually have very high levels of viremia; a false
positive test should be suspected if the viral load is <10,000 copies/mL. (See 'Viral
load' above.)

HIV seroconversion is usually detected between three to seven weeks after infection.
(See 'Serologic studies' above.)

The transmission of drug-resistant HIV strains may occur; thus, all patients should
have drug resistance testing after diagnosis, regardless of whether treatment is being
considered or not. (See 'Genotype resistance testing' above.)

All patients with suspected or confirmed acute HIV infection should be counseled to
adopt behaviors that guard against HIV transmission, including consistent and correct
condom use and avoidance of sharing injection drug use equipment. (See 'Prevention
counseling' above.)

Establishing the diagnosis of primary HIV infection is important from both the personal
and the public health perspective. Patients are typically highly infectious during acute
HIV due to an enormous viral burden in blood and genital secretions. (See 'Public
health implications' above.)

Since acute HIV infection is seldom recognized in clinical practice, data about
outcomes of early antiretroviral therapy are limited. Thus, it is currently unknown
whether treatment of acute HIV infection results in long-term virologic, immunologic, or
clinical benefit. (See 'Clinical studies' above.)

Given that antiretroviral therapy for acute infection remains controversial, enrollment in
a research study is encouraged to provide more information about the outcome of
early intervention. (See 'Patient management' above.)

With the shift to earlier therapy in asymptomatic prevalent infection and a reduction in
the toxicity of antiretroviral therapy, some guidelines now advocate that HIV treatment
be given to patients with acute symptomatic HIV infection.

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