BF Integrase Genes of HIV-1 Circulating in São Paulo, Brazil, with a Recurrent Recombination Region

Although some studies have shown diversity in HIV integrase (IN) genes, none has focused particularly on the gene evolving in epidemics in the context of recombination. The IN gene in 157 HIV-1 integrase inhibitor-naïve patients from the São Paulo State, Brazil, were sequenced tallying 128 of subtype B (23 of which were found in non-B genomes), 17 of subtype F (8 of which were found in recombinant genomes), 11 integrases were BF recombinants, and 1 from subtype C. Crucially, we found that 4 BF recombinant viruses shared a recurrent recombination breakpoint region between positions 4900 and 4924 (relative to the HXB2) that includes 2 gRNA loops, where the RT may stutter. Since these recombinants had independent phylogenetic origin, we argue that these results suggest a possible recombination hotspot not observed so far in BF CRF in particular, or in any other HIV-1 CRF in general. Additionally, 40% of the drug-naïve and 45% of the drug-treated patients had at least 1 raltegravir (RAL) or elvitegravir (EVG) resistance-associated amino acid change, but no major resistance mutations were found, in line with other studies. Importantly, V151I was the most common minor resistance mutation among B, F, and BF IN genes. Most codon sites of the IN genes had higher rates of synonymous substitutions (dS) indicative of a strong negative selection. Nevertheless, several codon sites mainly in the subtype B were found under positive selection. Consequently, we observed a higher genetic diversity in the B portions of the mosaics, possibly due to the more recent introduction of subtype F on top of an ongoing subtype B epidemics and a fast spread of subtype F alleles among the B population

Perceptions of HIV cure research among people living with HIV in Australia

Participation in HIV cure-related clinical trials that involve antiretroviral treatment (ART) interruption may pose substantial individual risks for people living with HIV (PLHIV) without any therapeutic benefit. As such, it is important that the views of PLHIV are considered in the design of HIV cure research trials. Examining the lived experience of PLHIV provides unique and valuable perspectives on the risks and benefits of HIV cure research. In this study, we interviewed 20 PLHIV in Australia about their knowledge and attitudes toward clinical HIV cure research and explored their views regarding participation in HIV cure clinical trials, including those that involve ART interruption. Data were analysed thematically, using both inductive and deductive coding techniques, to identity themes related to perceptions of HIV cure research and PLHIV’s assessment of the possible risks and benefits of trial participation. Study findings revealed interviewees were willing to consider participation in HIV cure research for social reasons, most notably the opportunity to help others. Concerns raised about ART interruption related to the social and emotional impact of viral rebound, including fear of onward HIV transmission and anxiety about losing control. These findings reveal the ways in which PLHIV perspectives deepen our understanding of HIV cure research, moving beyond a purely clinical assessment of risks and benefits in order to consider the social context

Analysis of the Origin and Evolutionary History of HIV-1 CRF28_BF and CRF29_BF Reveals a Decreasing Prevalence in the AIDS Epidemic of Brazil

HIV-1 subtype B and subtype F are prevalent in the AIDS epidemic of Brazil. Recombinations between these subtypes have generated at least four BF circulating recombinant forms (CRFs). CRF28_BF and CRF29_BF are among the first two BF recombinants being identified in Brazil and they contributed significantly to the epidemic. However, the evolution and demographic histories of the CRFs are unclear.A collection of gag and pol sequences sampled within Brazil was screened for CRF28_BF-like and CRF29_BF-like recombination patterns. A Bayesian coalescent framework was employed to delineate the phylogenetic, divergence time and population dynamics of the virus having CRF28_BF-like and CRF29_BF-like genotype. These recombinants were phylogenetically related to each other and formed a well-supported monophyletic clade dated to 1988-1989. The effective number of infections by these recombinants grew exponentially over a five-year period after their emergence, but then decreased toward the present following a logistic model of population growth. The demographic pattern of both recombinants closely resembles those previously reported for CRF31_BC.We revealed that HIV-1 recombinants of the CRF28_BF/CRF29_BF clade are still circulating in the Brazilian population. These recombinants did not exhibit a strong founder effect and showed a decreasing prevalence in the AIDS epidemic of Brazil. Our data suggested that multiple URFs may also play a role in shaping the epidemic of recombinant BF HIV-1 in the region

Phylodynamics of HIV-1 Circulating Recombinant Forms 12_BF and 38_BF in Argentina and Uruguay

<p>Abstract</p> <p>Background</p> <p>Although HIV-1 CRF12_BF and CRF38_BF are two epidemiologically important recombinant lineages circulating in Argentina and Uruguay, little is known about their population dynamics.</p> <p>Methods</p> <p>A total of 120 "CRF12_BF-like" and 20 "CRF38_BF-like" <it>pol </it>recombinant sequences collected in Argentina and Uruguay from 1997 to 2009 were subjected to phylogenetic and Bayesian coalescent-based analyses to estimate evolutionary and demographic parameters.</p> <p>Results</p> <p>Phylogenetic analyses revealed that CRF12_BF viruses from Argentina and Uruguay constitute a single epidemic with multiple genetic exchanges among countries; whereas circulation of the CRF38_BF seems to be confined to Uruguay. The mean estimated substitution rate of CRF12_BF at <it>pol </it>gene (2.5 × 10-3 substitutions/site/year) was similar to that previously described for subtype B. According to our estimates, CRF12_BF and CRF38_BF originated at 1983 (1978-1988) and 1986 (1981-1990), respectively. After their emergence, the CRF12_BF and CRF38_BF epidemics seem to have experienced a period of rapid expansion with initial growth rates of around 1.2 year^-1and 0.9 year^-1, respectively. Later, the rate of spread of these CRFs_BF seems to have slowed down since the mid-1990s.</p> <p>Conclusions</p> <p>Our results suggest that CRF12_BF and CRF38_BF viruses were generated during the 1980s, shortly after the estimated introduction of subtype F1 in South America (~1975-1980). After an initial phase of fast exponential expansion, the rate of spread of both CRFs_BF epidemics seems to have slowed down, thereby following a demographic pattern that resembles those previously reported for the HIV-1 epidemics in Brazil, USA, and Western Europe.</p

Eradication of HIV-1 latent reservoirs through therapeutic vaccination

Abstract Despite the significant success of combination anti-retroviral therapy to reduce HIV viremia and save lives, HIV-1 infection remains a lifelong infection that must be appropriately managed. Advances in the understanding of the HIV infection process and insights from vaccine development in other biomedical fields such as cancer, imaging, and genetic engineering have fueled rapid advancements in HIV cure research. In the last few years, several studies have focused on the development of “Kick and Kill” therapies to reverse HIV latency and kick start viral translational activity. This has been done with the aim that concomitant anti-retroviral treatment and the elicited immune responses will prevent de novo infections while eradicating productively infected cells. In this review, we describe our perspective on HIV cure and the new approaches we are undertaking to eradicate the established pro-viral reservoir

The role of CD32 during HIV-1 infection

Persistence of latent HIV-1 in long-lived resting memory CD4+ T cells is a major barrier to curing HIV-1 infection, and thus a biomarker for latently infected cells would be of great scientific and clinical importance.,,,, Through an elegant discovery-based approach, Descours et al. reported that CD32a, an Fcγ receptor not normally expressed on T cells, is a potential biomarker for latently infected cells. Using the quantitative viral outgrowth assay, we show that CD32+ CD4+ T cells do not harbor the majority of intact proviruses in the latent reservoir and that the enrichment found by Descours et al. may in part reflect the use of an ultrasensitive ELISA for HIV-1 p24 antigen that does not predict exponential viral outgrowth. Our studies show that CD32 is not a biomarker for the major population of latently infected CD4+ T cells