Acute Clinical Manifestations and Diagnosis of HIV

Symptoms and Signs of Acute HIV Infection

Different terms, including acute, recent, primary, and early HIV infection, have been used to describe initial exposure and infection with HIV. Regardless of the terminology, acute HIV infection is the period from the time of initial HIV infection until the stabilization of the viral load “set point” about 1 to 3 months later.

The usual time from any route of HIV exposure to the development of symptoms is 2 to 4 weeks, although incubation periods as long as 10 months have been observed. Typically, acute HIV infection presents with an acute retroviral syndrome, which is a constellation of nonspecific symptoms similar to a mononucleosis ( Chapter 348 ) or a flulike illness ( Chapter 331 ). Most symptoms associated with acute HIV infection are brief, but the severity and duration of symptoms can vary widely. Symptoms can include fever, lymphadenopathy, pharyngitis, rash, myalgia/arthralgia, diarrhea, anorexia, and weight loss ( Table 355-1 ). Headache, often described as retroorbital pain exacerbated by eye movement, frequently is reported.

No findings on physical examination are specific for acute HIV infection. Nontender lymphadenopathy, primarily involving the axillary, cervical, and occipital nodes, is common and often develops during the second week of illness. Nodes typically decrease in size following the acute presentation, but a modest degree of adenopathy may persist. Pharyngitis with pharyngeal edema and hyperemia is common, usually without tonsillar enlargement or exudate. Painful mucocutaneous ulceration is one of the most distinctive manifestations of acute HIV infection. These lesions may reflect mucocutaneous disease associated with coincident sexually transmitted infections, such as herpes simplex virus ( Chapter 345 ), syphilis ( Chapter 295 ), or chancroid ( Chapter 276 ). A generalized faint rash, which is also common, typically occurs 48 to 72 hours after the onset of fever and persists for 5 to 8 days. These lesions are characteristically small (5 to 10 mm), well-circumscribed, oval or round, pink to deeply red colored macules or maculopapules.

The acute retroviral syndrome can easily be missed or misdiagnosed unless the degree of suspicion is high. The differential diagnosis of acute HIV infection includes mononucleosis ( Chapter 348 ), toxoplasmosis ( Chapter 320 ), rubella ( Chapter 339 ), syphilis ( Chapter 295 ), disseminated gonococcal infection ( Chapter 275 ), viral hepatitis ( Chapter 134 ), and other viral infections.

The severity of the acute syndrome is associated with a higher viral load and a stronger innate immune response. ^, An estimated 10 to 40% of acute HIV infections are asymptomatic and can be diagnosed only later during routine screening or when symptoms or signs of immunosuppression develop.

Opportunistic infections and central nervous system manifestations may occur in some individuals during acute HIV infection. Oral and esophageal candidiasis ( Chapter 124 ; Figs. 310-1 and 397-5 ) is the most common opportunistic infection. Other infrequently reported infections include cytomegalovirus (proctitis, colitis, and hepatitis; Chapter 347 ), Pneumocystis jirovecii pneumonia ( Chapter 313 ), and cryptosporidiosis ( Chapter 321 ). More serious neurologic manifestations of acute HIV infection are unusual but can include aseptic meningitis, with severe headache, meningismus, photophobia, and a lymphocytic pleocytosis on cerebrospinal fluid (CSF) analysis. The presence of severe illnesses during acute infection may predict more rapid clinical progression to acquired immunodeficiency syndrome (AIDS).

Symptoms associated with acute HIV infection also can occur when patients who have well-controlled, established HIV infection discontinue suppressive antiretroviral therapy. In these cases, HIV viral levels rapidly rise from undetectable levels to as high as 1,000,000 copies/mL, CD4 counts drop appreciably, and symptoms (including fever, lymphadenopathy, and rash) develop in 10 days to 4 weeks after discontinuing all antiretroviral drugs.

Viral Load and Infectivity

In acute HIV infection, the viral RNA level is typically very high (10 ⁵ to 10 ⁷ copies/mL) within 2 weeks of infection, and the CD4 cell count can drop rapidly. Patients with acute HIV infection are highly contagious to others given the high HIV viral loads, which correlate with the risk of HIV transmission. In men with acute HIV infection, the viral load in semen appears to follow a similar pattern to that seen in blood, with the highest levels occurring at approximately 20 days after infection or 6 days after the onset of acute retroviral symptoms.

Concomitant with the evolution of HIV-specific immunity within the next several weeks, virus-specific CD8+ cytotoxic T lymphocytes appear, antibody seroconversion occurs, plasma HIV RNA levels fall precipitously by 2 to 3 logs, and the symptoms of the acute HIV infection resolve. In the absence of antiretroviral therapy, plasma HIV RNA levels will stabilize at an individual’s given “set point” within approximately 1 to 3 months after infection. Usually, the CD4 cell counts drop in relation to the initial increase in viral load, and CD8 cell counts increase. Following peak viremia, CD4 cell counts begin to rebound, and CD8 cell counts decline but do not generally return to baseline levels, thereby resulting in a persistent inversion of the normal CD4:CD8 ratio to less than 1. Additionally, elevations of liver enzymes, mild anemia, and thrombocytopenia can occur during acute HIV infection.

Rare individuals with HIV may retain normal CD4 counts and low or undetectable plasma viremia even in the absence of antiretroviral therapy. Individuals with persistent viral suppression, who are referred to as “elite controllers,” are distinguished from usual HIV patients who develop progressive disease by the persistence of HIV-specific T-helper cell proliferative responses. However, it is not clear whether these HIV immune responses directly cause or are the result of HIV control. Some data suggest that the initiation of antiretroviral therapy during acute infection protects activated HIV-specific T helper cells from infection by HIV, thereby preserving the HIV-specific cytotoxic T-lymphocyte response to virally infected cells. For example, patients who become infected despite preexposure prophylaxis ( Chapter 356 ) tend to have milder acute symptoms and lower viral loads. Preservation of the immune response to HIV may also shorten the duration of symptoms associated with acute infection, prevent dissemination of virus to other organs, and establish a lower virologic “set point.” Unfortunately, eradication of virus is currently unlikely because replication-competent HIV can be recovered from patients with suppressed viral loads. In addition, patients with prolonged virologic suppression still experience virologic rebound when treatment is stopped.