Among HIV-infected patients who initiated antiretroviral therapy (ART), patterns of cause-specific death varied by ART duration and were strongly related to age, sex, and transmission risk group. Deaths from non-AIDS malignancies were much more frequent than those from cardiovascular disease.
Kick&kill strategies combining drugs aiming to reactivate the viral reservoir with therapeutic vaccines to induce effective cytotoxic immune responses hold potential to achieve a functional cure for HIV-1 infection. Here, we report on an open-label, single-arm, phase I clinical trial, enrolling 15 early-treated HIV-1-infected individuals, testing the combination of the histone deacetylase inhibitor romidepsin as a latency-reversing agent and the MVA.HIVconsv vaccine. Romidepsin treatment resulted in increased histone acetylation, cell-associated HIV-1 RNA, and T-cell activation, which were associated with a marginally significant reduction of the viral reservoir. Vaccinations boosted robust and broad HIVconsv-specific T cells, which were strongly refocused toward conserved regions of the HIV-1 proteome. During a monitored ART interruption phase using plasma viral load over 2,000 copies/ml as a criterium for ART resumption, 23% of individuals showed sustained suppression of viremia up to 32 weeks without evidence for reseeding the viral reservoir. Results from this pilot study show that the combined kick&kill intervention was safe and suggest a role for this strategy in achieving an immune-driven durable viremic control.
The prognosis of human immunodeficiency virus (HIV) infection has improved in recent years with the introduction of antiretroviral treatment. While the frequency of AIDS-defining events has decreased as a cause of death, mortality from non-AIDS-related events including end-stage renal diseases has increased. The etiology of chronic kidney disease is multifactorial: immune-mediated glomerulonephritis, HIV-associated nephropathy, thrombotic microangiopathies, and so on. HIV infection is no longer a contraindication to transplantation and is becoming standard therapy in most developed countries. The HIV criteria used to select patients for renal transplantation are similar in Europe and North America. Current criteria state that prior opportunistic infections are not a strict exclusion criterion, but patients must have a CD4+ count above 200 cells/mm(3) and a HIV-1 RNA viral load suppressible with treatment. In recent years, more than 200 renal transplants have been performed in HIV-infected patients worldwide, and mid-term patient and graft survival rates have been similar to that of HIV-negative patients. The main issues in post-transplant period are pharmacokinetic interactions between antiretrovirals and immunosuppressants, a high rate of acute rejection, the management of hepatitis C virus coinfection, and the high cardiovascular risk after transplantation. More studies are needed to determine the most appropriate antiretroviral and immunosuppressive regimens and the long-term outcome of HIV infection and kidney graft.
Background The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV‐positive persons, and are available in print, online, and as a free App for download for iPhone and Android. Guideline highlights The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV‐positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre‐exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug−drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti‐hepatitis C virus (HCV) treatment with direct‐acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon‐containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. Conclusions The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview.
Background Strong and broad antiviral T-cell responses targeting vulnerable sites of HIV-1 will likely be a critical component for any effective cure strategy. Methods BCN01 trial was a phase I, open-label, non-randomized, multicenter study in HIV-1-positive individuals diagnosed and treated during early HIV-1 infection to evaluate two vaccination regimen arms, which differed in the time (8 versus 24 week) between the ChAdV63.HIVconsv prime and MVA.HIVconsv boost vaccinations. The primary outcome was safety. Secondary endpoints included frequencies of vaccine-induced IFN-γ + CD8 + T cells, in vitro virus-inhibitory capacity, plasma HIV-1 RNA and total CD4 + T-cells associated HIV-1 DNA. ( NCT01712425 ). Findings No differences in safety, peak magnitude or durability of vaccine-induced responses were observed between long and short interval vaccination arms. Grade 1/2 local and systemic post-vaccination events occurred in 22/24 individuals and resolved within 3 days. Weak responses to conserved HIV-1 regions were detected in 50% of the individuals before cART initiation, representing median of less than 10% of their total HIV-1-specific T cells. All participants significantly elevated these subdominant T-cell responses, which after MVA.HIVconsv peaked at median (range) of 938 (73-6,805) IFN-γ SFU/10 6 PBMC, representing on average 58% of their total anti-HIV-1 T cells. The decay in the size of the HIV-1 reservoir was consistent with the first year of early cART initiation in both arms. Interpretation Heterologous prime-boost vaccination with ChAdV63-MVA/HIVconsv was well-tolerated and refocused pre-cART T-cell responses towards more protective epitopes, in which immune escape is frequently associated with reduced HIV-1 replicative fitness and which are common to most global HIV-1 variants. Funding HIVACAT Catalan research program for an HIV vaccine and Fundació Gloria Soler. Vaccine manufacture was jointly funded by the Medical Research Council (MRC) UK and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreements (G0701669. Research in Context Evidence Before this Study: T cells play an important role in the control of HIV infection and may be particularly useful for HIV-1 cure by killing cells with reactivated HIV-1. Evidence is emerging that not all T-cell responses are protective and mainly only those targeting conserved regions of HIV-1 proteins are effective, but typically immunologically subdominant, while those recognizing hypervariable, easy-to-escape immunodominant ‘decoys’ do not control viremia and do not protect from a loss of CD4 T cells. We pioneered a vaccine strategy focusing T-cell responses on the most conserved regions of the HIV-1 proteome using an immunogen designat...
We modeled global time trends in median CD4 cell counts at combination antiretroviral therapy initiation in human immunodeficiency virus–infected adults. These counts have increased in all country income groups since 2002 but generally remained below 350/μL in 2015.
BackgroundEarly diagnosis of HIV infection can prevent morbidity and mortality as well as reduce HIV transmission. The aim of the present study was to assess prevalence, describe trends and identify factors associated with late presentation of HIV infection in Barcelona (Spain) during the period 2001-09.MethodsDemographic and epidemiological characteristics of cases reported to the Barcelona HIV surveillance system were analysed. Late presentation was defined for individuals with a CD4 count below 350 cells/ml upon HIV diagnosis or diagnosis of AIDS within 3 months of HIV diagnosis. Multivariate logistic regression were used to identify predictors of late presentation.ResultsOf the 2,938 newly diagnosed HIV-infected individuals, 2,507 (85,3%) had either a CD4 cell count or an AIDS diagnosis available. A total of 1,139 (55.6%) of the 2,507 studied cases over these nine years were late presenters varying from 48% among men who have sex with men to 70% among heterosexual men. The proportion of late presentation was 62.7% in 2001-2003, 51.9% in 2004-2005, 52.6% in 2006-2007 and 52.1% in 2008-2009. A decrease over time only was observed between 2001-2003 and 2004-2005 (p = 0.001) but remained constant thereafter (p = 0.9). Independent risk factors for late presentation were older age at diagnosis (p < 0.0001), use of injected drugs by men (p < 0.0001), being a heterosexual men (p < 0.0001), and being born in South America (p < 0.0001) or sub-Saharan Africa (p = 0.002).ConclusionLate presentation of HIV is still too frequent in all transmission groups in spite of a strong commitment with HIV prevention in our city. It is necessary to develop interventions that increase HIV testing and facilitate earlier entry into HIV care.
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