Impact of Combination Therapy for HIV Infection on Inpatient Census

Torres, Ramón A.; Barr, Michael R.

doi:10.1056/nejm199705223362118

Cited by 185 publications

(67 citation statements)

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“…In a review, Johnson and Gerber cited data demonstrating that HAART (a) can improve the ability to handle opportunistic infections, (b) allow discontinuation of treatment for opportunistic infections in some patients, (c) allow discontinuation of prophylaxis against some opportunistic infections, and (d) enhance responsiveness to vaccines [26]. In the lung HAART has been associated decreased opportunistic infections [33], decreased mycobacterial infections [34], and decreased incidence of bacterial pneumonia [35]. This improved immunologic milieu has led to the development of guidelines on when primary and secondary prophylaxis against opportunistic pathogens can be discontinued [36].…”

Section: Clinical Implications Of Haart On Pulmonary Disease In Hiv Imentioning

confidence: 99%

HIV-related lung disorders

Twigg

Knox

2007

Drug Discovery Today: Disease Mechanisms

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Highly active antiretroviral therapy (HAART) has dramatically altered the spectrum of morbidity and mortality in HIV-infected patients. This has been attributed to improvements in the lung microenvironment leading to enhanced pulmonary immunity, either by preventing the progressive loss of immune function or by actually promoting immune restoration. However, these changes have been accompanied by the recognition of new pulmonary complications in HIV-infected subjects, especially those associated with immune reconstitution. In this review we will describe how HIV infection alters the normal pulmonary environment, highlight the effect of HAART on these perturbations, and discuss potential complications of HAART in the lung, focusing on the pulmonary immune reconstitution inflammatory syndrome.

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Section: Clinical Implications Of Haart On Pulmonary Disease In Hiv Imentioning

confidence: 99%

HIV-related lung disorders

Twigg

Knox

2007

Drug Discovery Today: Disease Mechanisms

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“…As a result, the incidence of opportunistic infections has decreased and the life expectancy of HIV-infected persons has increased [3,4]. However, this has not occurred uniformly worldwide because antiretroviral therapy (ART) is not yet available to millions of HIVinfected people, mainly in resource-limited countries.…”

mentioning

confidence: 99%

Pulmonary infections in HIV-infected patients: an update in the 21st century

Benito¹,

Moreno²,

Miró³

et al. 2011

European Respiratory Journal

176

216

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From the first descriptions of HIV/AIDS, the lung has been the site most frequently affected by the disease. Most patients develop a pulmonary complication during the history of HIV infection, mainly of infectious aetiology.Important changes in the epidemiology of HIV-related pulmonary infections have occurred. Overall, prescription of Pneumocystis jirovecii prophylaxis and the introduction of highly active antiretroviral therapy (HAART) are the main causes.Currently, the most frequent diagnosis in developed countries is bacterial pneumonia, especially pneumococcal pneumonia, the second most frequent cause is Pneumocystis pneumonia and the third is tuberculosis. However, in Africa, tuberculosis could be the most common pulmonary complication of HIV.Pulmonary infections remain one of the most important causes of morbidity and mortality in these patients, and the first cause of hospital admission in the HAART era. Achieving an aetiological diagnosis of pulmonary infection in these patients is important due to its prognostic consequences.

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“…Due to its crucial role in viral replication, HIV-1 RT is an important target for anti-HIV drugs that currently include nucleoside reverse transcriptase inhibitors (NRTIs), i.e., zidovudine (AZT or ZDV), didanosine (ddI), stavudine (d4T), zalcitabine(ddC), lamivudine(3TC), emtricitabine (FTC), and abacavir (ABC) and a nucleotide reverse transcriptase inhibitor, tenofovir disoproxil fumarate (TDF), as well as the nonnucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), and etravirine (ETR). Both NRTIs and NNRTIs are key components of highly active antiretroviral therapy (HAART), which has led to significant declines in HIV-associated morbidity and mortality (23,33). However, the development of HIV drug resistance is a formidable obstacle to the long-term success of antiretroviral treatment (36,40), and resistance mutations have been described for all antiretroviral drugs currently in use (21).…”

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confidence: 99%

Compensation by the E138K Mutation in HIV-1 Reverse Transcriptase for Deficits in Viral Replication Capacity and Enzyme Processivity Associated with the M184I/V Mutations

Asahchop

Oliveira

et al. 2011

J Virol

161

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Recently, several phase 3 clinical trials (ECHO and THRIVE) showed that E138K and M184I were the most frequent mutations to emerge in patients who failed therapy with rilpivirine (RPV) together with two nucleos(t)ide reverse transcriptase inhibitors, emtricitabine (FTC) and tenofovir (TDF). To investigate the basis for the copresence of E138K and M184I, we generated recombinant mutated and wild-type (WT) reverse transcriptase (RT) enzymes and HIV-1 NL4-3 infectious clones. Drug susceptibilities were determined in cord blood mononuclear cells (CBMCs). Structural modeling was performed to analyze any impact on deoxynucleoside triphosphate (dNTP) binding. The results of phenotyping showed that viruses containing both the E138K and M184V mutations were more resistant to each of FTC, 3TC, and ETR than viruses containing E138K and M184I. Viruses with E138K displayed only modest resistance to ETR, little resistance to efavirenz (EFV), and no resistance to either FTC or 3TC. E138K restored viral replication capacity (RC) in the presence of M184I/V, and this was confirmed in cell-free RT processivity assays. RT enzymes containing E138K, E138K/ 184I, or E138K/184V exhibited higher processivity than WT RT at low dNTP concentrations. Steady-state kinetic analysis demonstrated that the E138K mutation resulted in decreased K m s for dNTPs. In contrast, M184I/V resulted in an increased K m for dNTPs compared to those for WT RT. These results indicate that the E138K mutation compensates for both the deficit in dNTP usage and impairment in replication capacity by M184I/V. Structural modeling shows that the addition of E138K to M184I/V promotes tighter dNTP binding.

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Impact of Combination Therapy for HIV Infection on Inpatient Census

Cited by 185 publications

References 0 publications

HIV-related lung disorders

HIV-related lung disorders

Pulmonary infections in HIV-infected patients: an update in the 21st century

Compensation by the E138K Mutation in HIV-1 Reverse Transcriptase for Deficits in Viral Replication Capacity and Enzyme Processivity Associated with the M184I/V Mutations

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