Acute HIV revisited: new opportunities for treatment and prevention

Abstract

Inability to recognize incident infection has traditionally limited both scientific and public health approaches to HIV disease. Recently, some laboratories have begun adding HIV nucleic acid amplification testing to HIV diagnostic testing algorithms so that acute (antibody-negative) HIV infections can be routinely detected within the first 1-3 weeks of exposure. In this review article, we will highlight critical opportunities for HIV treatment and prevention that are presented by these diagnostic strategies.

Figure 1

Acute HIV diagnostic timeline. Symptoms, when present, typically occur around 2 weeks after infection. Viremia is detectable prior to symptoms in the form of HIV p24 antigen (detectable by ELISA) or HIV RNA (detectable by even more sensitive nucleic acid amplification). While viremia reaches extremely high levels in the month or two following infection, p24 antigen typically becomes undetectable shortly before seroconversion, because of the formation of early antibody-antigen complexes. A secondary antibody-negative, p24 antigen–negative period is sometimes observed.

Figure 2

Specimen pooling for HIV RNA testing. The algorithm shown here is that used by the North Carolina State Laboratory of Public Health to increase the predictive accuracy and cost efficiency of the screening of all sera, obtained through HIV voluntary counseling and testing, that are initially antibody-negative for HIV RNA. (A) Illustration of the creation of intermediate and master pools in a 1:10:90 pyramid-style pooling scheme. Only HIV-seronegative specimens are pooled. In each step, 200-μl aliquots are drawn off for pooling. The master pool ultimately contains sera from 90 antibody-negative individuals. (B) Illustration of the manner in which pools are screened using HIV RNA amplification testing. Positive results on a master pool trigger testing of intermediate pools and, in the final round of testing, individual specimens. When only a small number of specimens in a population are truly HIV RNA–positive, this procedure results in a dramatic reduction in the number of RNA tests used and virtually eliminates false-positive RNA test results in the final round of testing. Figure reprinted with permission from Journal of the American Medical Association (16).

Figure 3

HIV transmission and the establishment of HIV reservoirs. (A) Interactions of HIV envelope glycoproteins, CD4, and CCR5 or CXCR4 coreceptors trigger fusion and entry of HIV. (B) Outline of the sequence and time course of events involved in viral dissemination. Figure adapted with permission from New England Journal of Medicine (98, 99).

Figure 4

Similarity in the dynamics of viremia and genital shedding in experimentally HIV- or SHIV-infected macaques. (A and B) Virion-associated RNA (vRNA) levels in blood plasma (A) and seminal plasma (B), observed in pig-tailed macaques during the first 12 weeks after intravenous (n = 4; filled symbols) or intrarectal exposure (n = 4; open symbols and dashed lines) to HIV type 2 (HIV_GB122). (C and D) vRNA levels in blood plasma (C) and seminal plasma (D) through 12 weeks after intravenous exposure (n = 2) to simian/HIV (SHIV_89.6p) are also shown. Peak viremia and peak genital shedding occur simultaneously and resolve over a similar time frame in each model. Figure modified with permission from Journal of Infectious Diseases (83).