Are there benefits to starting antiretroviral therapy during primary HIV infection? Conclusions from the Seattle Primary Infection Cohort vary by control group

Department of Medicine, University of Washington, Seattle, WA, USA.
International Journal of STD & AIDS (Impact Factor: 1.05). 03/2012; 23(3):201-6. DOI: 10.1258/ijsa.2011.011178
Source: PubMed


It is controversial whether starting combination antiretroviral therapy (cART) during primary HIV infection (PHI) is beneficial. Subjects in this observational cohort began cART <30 days (group 1: acute treatment, n = 40), 31-180 days (group 2: early treatment, n = 82) or >180 days (group 3: delayed treatment, n = 35) after HIV infection, and were compared with 27 historical and 60 contemporary controls. Time to HIV-related diagnoses did not differ for group 1 (adjusted hazard ratio [aHR] 1.44, P = 0.3) or group 2 (aHR 1.17, P = 0.5) compared with contemporary controls, but it was delayed for both treated groups (aHR 0.38 for group 1, P = 0.01; and aHR 0.28 for group 2, P < 0.0001) compared with historical controls. Although rates of HIV-related diagnoses were similar in acutely treated subjects and contemporary controls, results were confounded by associations between higher CD4 counts, lower HIV RNA levels and delayed disease progression as reasons for deferring treatment. Randomized trials are needed to address benefits of cART during PHI.

Download full-text


Available from: Robert Wellman, Aug 26, 2014
  • Source
    • "At Gay City, all counselors participated , and the study was offered primarily to men considered to be at higher risk for HIV acquisition; this included men with symptoms of acute infection, who reported sex with an HIV-infected partner, or who had a condom break or had no recollection of events during or after a sexual exposure. Finally, to enrich the analysis with persons with early infection, study enrollment was offered to persons referred to the PIC [22] for suspected or confirmed diagnosis of acute HIV infection. The University of Washington Institutional Review Board approved this study, and all participants gave verbal consent. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Point-of-care (POC) rapid HIV tests have sensitivity during the "window period" comparable only to earliest generation EIAs. To date, it is unclear whether any POC test performs significantly better than others. Compare abilities of POC tests to detect early infection in real time. Men who have sex with men (MSM) were recruited into a prospective, cross-sectional study at two HIV testing sites and a research clinic. Procedures compared four POC tests: one performed on oral fluids and three on fingerstick whole blood specimens. Specimens from participants with negative POC results were tested by EIA and pooled nucleic acid amplification testing (NAAT). McNemar's exact tests compared numbers of HIV-infected participants detected. Between February 2010 and May 2013, 104 men tested HIV-positive during 2479 visits. Eighty-two participants had concordant reactive POC results, 3 participants had concordant non-reactive POC tests but reactive EIAs, and 8 participants had acute infection. Of 12 participants with discordant POC results, OraQuick ADVANCE Rapid HIV-1/2 Antibody Test performed on oral fluids identified fewer infections than OraQuick performed on fingerstick (p=.005), Uni-Gold Recombigen HIV test (p=.01), and determine HIV-1/2 Ag/Ab combo (p=.005). These data confirm that oral fluid POC testing detects fewer infections than other methods and is best reserved for circumstances precluding fingerstick or venipuncture. Regardless of specimen type, POC tests failed to identify many HIV-infected MSM in Seattle. In populations with high HIV incidence, the currently approved POC antibody tests are inadequate unless supplemented with p24 antigen tests or NAAT.
    Full-text · Article · Dec 2013 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology
  • Source
    • "RNA was extracted from five plasma specimens from one HIV-1 infected individual from the Seattle Primary Infection Cohort (Schacker et al., 1996; Stekler et al., 2012) using the QIAamp Viral RNA Mini Kit (Qiagen, Valencia, CA) according to the manufacturer's protocol. A total of 560 ml of plasma was extracted in each case and eluted in 80 ml of elution buffer. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Pyrosequencing technology provides an important new approach to more extensively characterize diverse sequence populations and detect low frequency variants. However, the promise of this technology has been difficult to realize, as careful correction of sequencing errors is crucial to distinguish rare variants (∼1%) in an infected host with high sensitivity and specificity. We developed a new approach, referred to as Indel and Carryforward Correction, or ICC, to cluster sequences without substitutions and locally correct only indel and carryforward sequencing errors within clusters to ensure that no rare variants are lost. ICC performs sequence clustering in the order of (a) homopolymer indel patterns only, (b) indel patterns only, and (c) carryforward errors only, without the requirement of a distance cut-off value. Overall, ICC removed 93%-95% of sequencing errors found in control data sets. On pyrosequencing data from a PCR fragment derived from 15 HIV-1 plasmid clones mixed at various frequencies as low as 0.1%, ICC achieved the highest sensitivity and similar specificity compared to other commonly used error correction and variant calling algorithms.Availability and implementation: Source code is freely available for download at It is implemented in Perl and supported on Linux, Mac OS X and MS Windows. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
    Full-text · Article · Jul 2013 · Bioinformatics
  • [Show abstract] [Hide abstract]
    ABSTRACT: U.S. guidelines recommend genotyping for persons newly diagnosed with HIV infection to identify transmitted drug resistance mutations associated with decreased susceptibility to NRTIs, NNRTIs, and PIs. To date, testing for integrase strand transfer inhibitor (INSTI) mutations has not been routinely recommended. We aimed to evaluate the prevalence of transmitted INSTI mutations among persons with primary HIV-1 infection in Seattle, WA. Persons with primary HIV-1 infection have enrolled in an observational cohort at the University of Washington Primary Infection Clinic since 1992. We performed a retrospective analysis of plasma specimens collected prospectively from the 82 antiretroviral-naive subjects who were enrolled from 2007-13, after FDA-approval of the first INSTI. Resistance testing was performed by consensus sequencing. Specimens for analysis had been obtained a median of 24 (IQR 18-41, range 8-108) days after the estimated date of HIV-1 infection. All subjects were infected with HIV-1 subtype B except for one subject infected with subtype C. Consensus sequencing identified no subjects with major INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R, N155H). Using exact binomial confidence intervals, the upper bound of the 95% CI was 4.4%. Although our sample size was small, this study does not support the need at this time to evaluate integrase mutations as part of routine consensus sequencing among persons newly diagnosed with HIV-1 infection. However, it is likely that the prevalence of transmitted INSTI mutations may increase with the recent commercial introduction of additional INSTIs and presumably greater INSTI use among persons living with HIV-1.
    No preview · Article · May 2014 · Antiviral therapy
Show more