Relative likelihood of new diagnosis of HIV infection among all HIV positive patients.

<p>Relative likelihood of new diagnosis of HIV infection among all HIV positive patients.</p

Characteristics of all participants stratified by testing acceptance (N = 2355).

<p>Characteristics of all participants stratified by testing acceptance (N = 2355).</p

Patient enrollment and testing acceptance overview.

<p>Patient enrollment and testing acceptance overview.</p

Characteristics of participants who consented to HIV testing or knew their HIV status, stratified by HIV status (N = 1852).

<p>Characteristics of participants who consented to HIV testing or knew their HIV status, stratified by HIV status (N = 1852).</p

Contrasting antibody responses to intrasubtype superinfection with CRF02_AG

<div><p>HIV superinfection describes the sequential infection of an individual with two or more unrelated HIV strains. Intersubtype superinfection has been shown to cause a broader and more potent heterologous neutralizing antibody response when compared to singly infected controls, yet the effects of intrasubtype superinfection remain controversial. Longitudinal samples were analyzed phylogenetically for <i>pol</i> and <i>env</i> regions using Next-Generation Sequencing and envelope cloning. The impact of CRF02_AG intrasubtype superinfection was assessed for heterologous neutralization and antibody binding responses. We compared two cases of CRF02_AG intrasubtype superinfection that revealed complete replacement of the initial virus by superinfecting CRF02_AG variants with signs of recombination. NYU6564, who became superinfected at an early time point, exhibited greater changes in antibody binding profiles and generated a more potent neutralizing antibody response post-superinfection compared to NYU6501. In contrast, superinfection occurred at a later time point in NYU6501 with strains harboring significantly longer V1V2 regions with no observable changes in neutralization patterns. Here we show that CRF02_AG intrasubtype superinfection can induce a cross-subtype neutralizing antibody response, and our data suggest timing and/or superinfecting viral envelope characteristics as contributing factors. These results highlight differential outcomes in intrasubtype superinfection and provide the first insight into cases with CRF02_AG, the fourth most prevalent HIV-1 strain worldwide.</p></div

Timeline and clinical parameters of the two cases of intrasubtype CRF02_AG superinfection.

<p><b>A)</b> Plasma samples were collected from 2002 to 2014 for patients NYU6501 and NYU6564. Samples are shown in green along the timeline. Red indicates the time span when superinfection occurred. Blue indicates antiretroviral treatment (ART). <b>B)</b> Collection dates, viral load, CD4 cell counts, and the time post diagnosis for each sample used in the study (mths abbreviates for months when listed). Red shades indicate the first time point collected after superinfection occurred. Blue shades highlight samples taken when the patient was on ART. Time points after superinfection are in bold.</p

Penile HIV shedding, wound healing, and resumption of sex stratified by plasma viral load and ART status.

<p>The day 0 visit is prior to surgery. (A) HIV shedding from MC wounds increased at 7, 14, and 21 d after MC. The open symbols are the empirical data, and the filled symbols and line are the fit estimates. The error bars represent the 95% CIs of the fitted values. (B) There was no difference in certified wound healing between the three ART/VL groups. (C) There was no difference in the proportion of men resuming sex between the three ART/VL groups.</p

Diversity and divergence over time for 34 individuals for both p24 and gp41.

<p>Top Row: Mean pairwise diversity at first, second, and third codon positions over time for individuals (represented in yellow, pink, and light blue, respectively). The average change in mean pairwise diversity over time was inferred by linear regression. Bottom Row: Mean nonsynonymous (purple) and synonymous divergence (blue) over time for individuals.</p

Evolutionary rates for p24 and gp41 at the within- and between-hosts scales measured in substitutions per site per year (subs/site/year).

<p>The within-host nonsynonymous (filled circles) and synonymous (open circles) substitution rates were estimated for p24 and gp41 for all 34 individuals, which are ordered from left to right (subtype A, pink; subtype C, green; subtype D, yellow). Blue and white columns correspond to the individual estimates. The estimates in the grey background indicate the between-host substitution rates for subtypes A, C, and D. The vertical lines represent the 95% credible intervals (solid lines, nonsynonymous; dashed lines, synonymous).</p

Study flow diagram.

<p>The retention (asterisk) indicates the number (percent) of men at each follow-up visit.</p