Uncommon Signs and Symptoms of Early HIV Infection

Study Shows That Serious, "Later Stage" Illnesses Can Accompany Early Infection

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While there has been much published on the early signs and symptoms of HIV, there is still no widely agreed definition as to how a "typical" infection might present itself in the early (acute) stages. And that's a problem.

Despite government efforts to increase HIV testing among all Americans ages 15 to 65, many people will wait until such time as the "early signs" of infection appear. The fact that the newest infections will present with absolutely no symptoms only exacerbates the issue and may explain why 20% of the 1.2 million Americans living with HIV remain undiagnosed.

To complicate matters even further, for those who do have symptoms, research now suggests that anywhere from 25-40% will present with conditions not typically associated with HIV. As a result, it is likely that new infections are being either missed or misdiagnosed—and not just by the infected individual but by the treaters themselves.

Such non-typical symptoms of early infection can include diseases of the gastrointestinal and central nervous system, as well as the eyes, lungs, kidneys, liver, and genitals.  

Common and Uncommon Symptoms of Early HIV

Typically speaking, around 40% of newly infected individuals will experience signs of  acute retroviral syndrome (or ARS). ARS is simply the body's response to HIV as it mounts a defense against the viral invader, with the ensuing inflammation causing symptoms similar to that of the flu.

Fever, fatigue, headache, sore throat, swollen lymph glands, and muscle/joint pain are not uncommon features of ARS.

Others might develop a rash (often referred to as an "HIV rash"), which can manifest with bumpy patches, generally on the upper half of the body. Other still might experience short-term nausea, vomiting, or stomach pain.

While these are considered the most common signs of ARS, an increasing body of evidence seems to suggest that some might experience more serious conditions, even life-threatening ones.

In 2015, scientists with the Zurich Primary HIV Prevention Study in Switzerland aimed to establish the range and frequency of symptoms that can occur during acute HIV infection. According to the research, not only were they able to identify 18 different illnesses or conditions—far more than had been previously established—they reported a significant number has been missed in initial diagnosis.

Only patients identified during early infection were included, defined as:

  • Acute HIV infection, meaning that a person had either presented with symptoms along with a negative or indeterminate HIV test, or had no symptoms but has tested positive for HIV within 90 days of a known exposure.
  • Recent HIV infection, meaning that a person presented with symptoms along with a positive HIV test, or had no symptoms but had tested positive for HIV within 90-180 days of a known exposure.

The results were surprising. Of the 290 patients who satisfied the recruitment criteria, 25% had symptoms not typically associated with ARS.

Among those with symptoms, the incidence grew even greater, with 28.5% of acute and 40% of recent patients experiencing atypical HIV- and non-HIV-related illnesses.

Among them, 23% presented with an AIDS-defining condition, meaning that their very first sign of infection was an illness typically seen in later-stage disease. These included cases of esophageal candida (thrush, cytomegalovirus (CMV) of the gut or liver, herpes zoster (shingles), and even a case of HIV wasting syndrome, a condition almost exclusively associated with advanced infection.

Non-HIV-associated gastrointestinal symptoms were next on the list, accounting for 14% of atypical presentations. Nearly half were cases of tonsillitis, while more serious manifestations included severe gastric bleeding, gall bladder inflammation, kidney failure, and a herpes-related infection (which was not only misdiagnosed as appendicitis but later resulted in the partial removal of the patient's colon). 

Central nervous system (CNS) symptoms accounted for further 12% of atypical cases. Among these, hospitalizations were reported in patients with severe brain inflammation (encephalitis) and meningitis. Transient facial paralysis was also regularly noted, as were cases of acute psychiatric episodes.

More concerningly perhaps, almost half of these cases received a diagnosis other than HIV before finally being tested for the virus.

So What Does This Tell Us?

In the past, we might have reasonably presumed that a person presenting with a serious, HIV-related illness was simply infected years ago and was only now just becoming symptomatic. We now understand that, in some patients, serious disease can accompany even the earliest stages of infection.

Even more surprisingly, we now know that these conditions tend to occur in patients with healthier immune systems. According to the research, individuals with a stronger immune response (i.e., a CD4 count over 500 cells/mL) who were more likely experience a severe acute episode than someone with a moderately suppressed system.

While the mechanisms for these disorders are not entirely clear, we do know that certain factors can increase their likelihood, including an extremely high viral load in early infection (average 4-5 million copies/mL) and the type of virus the person is infected with (specifically the non-B HIV subtype).

We are also gaining greater insight into the rate and extent of HIV infiltration in the gut and brain, and the factors that might predispose a person to serious gastrointestinal and CNS infections.

From an individual standpoint, the research strongly supports the government's call for HIV testing of all Americans ages 15-65 as part of doctor's visit. No longer can we presume a person to be at low risk simply because he or she is not presenting with "classical" sign of infection.

While the Swiss researchers concluded that the real-world incidence of atypical acute symptoms may be only around 15%, that's still translate one out of eight potentially missed diagnoses. And with HIV infection rates rising in many at-risk populations (including men who have sex with men and African Americans), that's one in eight we simply cannot afford to miss.


Braun, D.; Kouyos. R.; Balmer, B.; et al. "Frequency and spectrum of unexpected clinical manifestations of primary HIV-1 infection." Clinical Infectious Diseases. 2015; 61(6):1013-1021.

Cohen, M.; Gay, C.; Busch, P.; and Hecht, F. "The Detection of Acute HIV Infection." The Journal of Infectious Diseases. 2010; 202(Supplement 2):S270-S277.

Moyer, V. "Screening for HIV: U.S. Preventive Services Task Force Recommendation Statement." April 30, 2013. Annals of Internal Medicine. April 30, 2013; doi:10.7326/0003-4819-159-1-201307020-0064.

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