Joanne D. Stekler

Hiv Serosorting in Men Who Have Sex With Men: Is It Safe?

Background:Serosorting is the practice of preferentially having sex with partners of concordant HIV status or of selectively using condoms with HIV-discordant partners. Methods:We evaluated the epidemiology of serosorting among men who have sex with men (MSM) seen in a sexually transmitted disease clinic, Seattle, WA, 2001-2007, and defined the percentage of visits during which MSM tested HIV positive based on whether they reported nonconcordant unprotected anal intercourse (UAI), UAI only with partners thought to be HIV negative (serosorters), no UAI, or no anal intercourse. Results:Men reported serosorting during 3295 (26%) of 12,449 visits. From 2001 to 2007, the proportion of visits during which men reported serosorting increased (P = 0.02); this change was greater among HIV-infected MSM than among HIV-uninfected MSM. Among men who tested HIV negative in the preceding year, HIV tests were positive in 49 (3.5%) of 1386 who reported nonconcordant UAI, 40 (2.6%) of 1526 serosorters, 28 (1.5%) of 1827 who had only protected anal intercourse, and 0 of 410 who had no anal intercourse (P < 0.0001); 32% of new HIV infections occurred in serosorters. The prevalence of HIV was higher among serosorters tested during 2004-2007 than among those tested during 2001-2003 (0.85% vs. 3.2%, P = 0.03). Conclusions:Serosorting offers MSM limited protection from HIV.

Targeted screening for primary HIV infection through pooled HIV-RNA testing in men who have sex with men

HIV-RNA testing may identify individuals with primary HIV infection. Men who have sex with men (MSM) having HIV testing through Public Health, Seattle and King County were screened for primary infection through pooled RNA testing. Eighty-one out of 3525 specimens (2.3%) had detectable antibody and RNA, and seven out of 3439 antibody-negative specimens (0.2%) had HIV RNA. Targeted screening for primary infection through pooled RNA testing in MSM is a useful addition to HIV case finding.

Population-based metrics for the timing of HIV diagnosis, engagement in HIV care, and virologic suppression

Objective:To compare population-based metrics for assessing progress toward the US National HIV/AIDS Strategy (NHAS) goals. Design:Analysis of surveillance data from persons living with HIV/AIDS (PLWHA) in King County, Washington, USA, 2005–2009. Methods:We examined indicators of the timing of HIV diagnosis [intertest interval, CD4 cell count at diagnosis, and AIDS ⩽ 1 year of diagnosis (late diagnosis)]; linkage to initial care (CD4 or viral load report ⩽3 months after diagnosis) and sustained care (a laboratory report 3–9 months after linkage); engagement in continuous care in 2009 (at least two laboratory reports ≥3 months apart); and virologic suppression. Results:Thirty-two percent of persons had late HIV diagnoses, 31% of whom reported testing HIV negative in the 2 years preceding their HIV diagnoses. Linkage to sustained care, but not linkage to initial care, was significantly associated with subsequent virologic suppression. Among 6070 PLWHA in King County, 65% of those with at least one viral load reported in 2009 and 53% of all PLWHA had virologic suppression. Although only 66% of all PLWHA were engaged in continuous care, 81% were defined as engaged using the denominator proposed in the NHAS (at least one laboratory result reported in 2009 excluding persons establishing care in the second half of the year). Conclusions:Proposed metrics for monitoring the HIV care continuum may not accurately measure late diagnoses or linkage to sustained care and are sensitive to assumptions about the size of the population of PLWHA. Monitoring progress toward achievement of NHAS goals will require improvements in HIV surveillance data and refinement of care metrics.

Demographic Processes Affect HIV-1 Evolution in Primary Infection before the Onset of Selective Processes

ABSTRACT HIV-1 transmission and viral evolution in the first year of infection were studied in 11 individuals representing four transmitter-recipient pairs and three independent seroconverters. Nine of these individuals were enrolled during acute infection; all were men who have sex with men (MSM) infected with HIV-1 subtype B. A total of 475 nearly full-length HIV-1 genome sequences were generated, representing on average 10 genomes per specimen at 2 to 12 visits over the first year of infection. Single founding variants with nearly homogeneous viral populations were detected in eight of the nine individuals who were enrolled during acute HIV-1 infection. Restriction to a single founder variant was not due to a lack of diversity in the transmitter as homogeneous populations were found in recipients from transmitters with chronic infection. Mutational patterns indicative of rapid viral population growth dominated during the first 5 weeks of infection and included a slight contraction of viral genetic diversity over the first 20 to 40 days. Subsequently, selection dominated, most markedly in env and nef. Mutants were detected in the first week and became consensus as early as day 21 after the onset of symptoms of primary HIV infection. We found multiple indications of cytotoxic T lymphocyte (CTL) escape mutations while reversions appeared limited. Putative escape mutations were often rapidly replaced with mutually exclusive mutations nearby, indicating the existence of a maturational escape process, possibly in adaptation to viral fitness constraints or to immune responses against new variants. We showed that establishment of HIV-1 infection is likely due to a biological mechanism that restricts transmission rather than to early adaptive evolution during acute infection. Furthermore, the diversity of HIV strains coupled with complex and individual-specific patterns of CTL escape did not reveal shared sequence characteristics of acute infection that could be harnessed for vaccine design.

Env length and N-linked glycosylation following transmission of human immunodeficiency virus Type 1 subtype B viruses.

Whether there is selection for specific viral Env variants upon HIV-1 transmission is controversial. We examined the V1V2 and V1V4 regions of Env in 10 new and 8 previously described transmission pairs infected with HIV-1 subtype B, including a total of 9 pairs in which the infecting partner had developed substantial viral diversity prior to transmission. We found that during transmission of HIV-1 subtype B, as well as for other subtypes reported in the past, viral populations in recipients undergo substantial genetic bottlenecks, as well as weak evidence for a propensity to replicate viruses with shorter variable loops and fewer potential N-linked glycosylation sites.

Detection of acute HIV infection: we can't close the window.

Acute human immunodeficiency virus (HIV) infection poses a dilemma for diagnosis, clinical management, and public health. It has been variously defined as the transient symptomatic illness associated with high-titer viral replication [1], the period from initial infection to complete seroconversion [2], and the phase between the appearance of detectable HIV RNA and detectable antibodies to HIV [3]. In the context of therapeutic trials, primary HIV infection includes the acute infection interval and the first 6 months after seroconversion, during which viral set point is established [4, 5]. ‘‘Detecting acute infection’’ has also been used synonymously with ‘‘closing the window,’’ the period during which tests for HIV are negative in persons who are infected. In this issue of the journal, Rosenberg et al [6] evaluated how well the Determine HIV-1/2 Ag/Ab Combo rapid test (Combo RT) compared with an algorithm of parallel antibody tests followed by RNA polymerase chain reaction. The Combo RT, designed for use at the point of care with finger-stick whole blood to detect HIV antibody and HIV antigen (and distinguish the two) in 20 minutes, did not fare very well in this comparison. The Combo RT is a lateral flow test (ie, an immunoassay that incorporates all necessary reagents into a single test strip). The test result is read visually, without instrumentation, after the specimen flows across the strip. Lateral flow tests have revolutionized HIV testing because they are easy to perform, require minimal training, have long-term stability, require no dedicated instrumentation, and can use whole blood specimens. In the United States, lateral flow HIV tests are used extensively in nonclinical settings. However, high hopes for point-of-care rapid tests able to identify acute infection, predicated on detecting p24 antigen, may be unrealistic. Recently developed fourthgeneration HIV antigen-antibody (Ag/Ab) combination assays, designed for use in the laboratory, detect both p24 antigen and antibodies against HIV but do not distinguish between the two. They exhibit an analytic sensitivity for p24 antigen of 11–18 pg/mL [7], equivalent to approximately 30 000–50 000 copies/mL of HIV RNA [8]. In contrast, lateral flow assays using colloidal gold have a lower limit of detection in the range of 1 ng/mL [9], 100-fold higher than the p24 antigen concentration usually present in plasma [8]. With the ultrasensitive procedure that includes heat dissociation of p24 antigen–antibody immune complexes, signal amplification, and instrumentation, the limit of detection for p24 (without additional pretreatment of the specimen to disrupt viral particles) can be

Concurrent Sexually Transmitted Infections (STIs) in Sex Partners of Patients with Selected STIs: Implications for Patient-Delivered Partner Therapy

250 000 RNA copies/mL [10]. The findings of Rosenberg et al substantiate this: ultrasensitive methods were used to test 7 of the 8 acute specimens and failed to detect p24 antigen in 2 that had RNA concentrations of 45 000 and

HIV dynamics in seminal plasma during primary HIV infection

750 000 copies/mL. In contrast, the ability of the Combo RT to establish the presence of antibodies to HIV was excellent. The Combo RT was positive for antibody in 162 (99.4%) of the 163 persons with established infection and in 2 of the 8 patients with acute HIV infection who were negative on other antibody tests. This latter finding suggests that the Combo RT might be able to identify many of the earliest infections. As shown in Table 1, antibody tests differ in their sensitivity to detect HIV during seroconversion [11]. Most lateral flow rapid tests in current use (and also Western blot analysis) are based on second-generation immunoassay principles that detect only immunoglobulin (Ig) G–class antibodies and become positive, on average, 20–25 days after RNA appears [12]. The antibody component of the Combo RT detects both IgMand IgGclass antibodies. Several studies suggest Received and accepted 9 November 2011; electronically published 29 December 2011. Correspondence: Bernard M. Branson, MD, CDC, 1600 Clifton Rd, MS D-21, Atlanta, GA 30333 (bbranson@cdc.gov). The Journal of Infectious Diseases 2012;205:521–4 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011. DOI: 10.1093/infdis/jir793

Abacavir hypersensitivity reaction in primary HIV infection.

BACKGROUND Patient-delivered partner therapy (PDPT) is the practice of providing disease-specific antimicrobial agents to patients for delivery to their sex partners. Some partners who receive PDPT may forgo clinical evaluation, resulting in missed opportunities for the diagnosis and treatment of comorbid conditions. METHODS We conducted a review of electronic charts for 8623 individuals attending 4 sexually transmitted disease clinics who were sex partners of patients with selected sexually transmitted infections (STIs). We evaluated the concordance between STIs diagnosed in partners and their reported exposures for which they might have received PDPT. RESULTS Among 3503 female and 4647 heterosexual male partners, 19 (0.4%) of 4716 individuals tested were newly diagnosed with human immunodeficiency virus (HIV) infection, and 61 individuals (0.7%) had syphilis. Pelvic inflammatory disease was diagnosed in 133 women (3.8%). Seventy-two (3.2%) of 2226 female and heterosexual male partners reporting exposure to patients with chlamydial infection had gonorrhea diagnosed. Chlamydial infection or gonorrhea was diagnosed in 81 heterosexual male partners (10.3%) who reported contact with women with trichomoniasis. Among 473 men who have sex with men (MSM; including bisexual men), 13 (6.3%) of 207 tested were newly diagnosed with HIV infection, and 8 (1.7%) had syphilis. Six (6.1%) of 98 MSM reporting exposure to patients with chlamydial infection had gonorrhea diagnosed. CONCLUSIONS Infrequent coinfections in female and heterosexual male partners exposed to patients with chlamydial infection or gonorrhea would not preclude use of PDPT. However, PDPT for male partners of women with trichomoniasis and for MSM requires further study.

Replacing clinic-based tests with home-use tests may increase HIV prevalence among Seattle men who have sex with men: evidence from a mathematical model.

HIV dynamics in seminal plasma during primary HIV infection was evaluated through an observational study of individuals with primary HIV infection at the University of Washington Primary Infection Clinic. Seminal plasma HIV RNA was quantified using a real-time reverse transcription PCR assay. Blood plasma RNA was quantified by bDNA or PCR-based assays. Longitudinal analyses of HIV RNA levels over time used random effects regression analysis. From 1993 to 2005, 110 men collected 327 semen specimens. Initial blood and seminal plasma RNA levels in untreated men were only moderately correlated (Spearman r = 0.38, p = 0.0002). Estimated peak and set point levels were lower in semen than blood by 0.8 (p = 0.001) and 0.7 (p < 0.001) log(10) copies/ml, respectively. RNA decay rates were similar in the two compartments (p = 0.4). For 2 months after infection, mean HIV RNA levels in seminal plasma remained above a threshold level (3.8 log(10) copies/ml) that has been associated with recovery of infectious virus in vitro. HIV-positive men are likely to be most infectious in the first months following HIV acquisition. However, the modest relationship between HIV RNA levels in blood and seminal plasma suggests that the relative risk of HIV transmission during primary infection may vary from current estimates that are solely based on blood levels. Incorporating seminal plasma HIV levels into future mathematical models may increase the accuracy of these models.