scholarly journals Burden of Disease in PWH Harboring a Multidrug-Resistant Virus: Data From the PRESTIGIO Registry

2020 ◽  
Vol 7 (11) ◽  
Author(s):  
Laura Galli ◽  
Maria Rita Parisi ◽  
Andrea Poli ◽  
Marianna Menozzi ◽  
Marta Fiscon ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Burden Of Disease ◽  
Cox Regression ◽  
Multidrug Resistant ◽  
Strand Transfer ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Clinical Events ◽  
Lower Baseline ◽  
History Of

Abstract Background Currently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population. Methods This was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Cox regression models evaluated factors associated with the risk of new clinical events/death. Results Among 148 PWH followed for a median (interquartile range) of 47 (32–84) months after 4DR evidence, 38 PWH had 62 new events or died from any cause (incidence rate, 9.12/100 person-years of follow-up; 95% CI = 6.85–11.39): 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADEs, 32 NADEs; 20 of the 38 NADEs (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95% CI, 3%–13%), and that of ≥1 event or death was 22% (95% CI, 16%–31%). A higher risk of new clinical events/death was more likely in PWH with previous clinical events (adjusted hazard ratio [aHR], 2.67; 95% CI, 1.07–6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR, 0.82; 95% CI, 0.65–1.02). Conclusions PWH harboring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio.

scholarly journals Diabetes and HIV

2019 ◽  
Vol 7 (02) ◽  
pp. 45-49
Author(s):  
Ranabir Salam ◽  
Sarita Bajaj ◽  
Nitin Kapoor ◽  
Banshi Saboo ◽  
Arundhati Dasgupta
Keyword(s):  
Diabetes Mellitus ◽  
Reverse Transcriptase ◽  
People Living With Hiv ◽  
Reverse Transcriptase Inhibitors ◽  
First Line ◽  
Hiv Patients ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Family History Of Diabetes ◽  
Drug Of Choice ◽  
History Of

AbstractIn India, the prevalence of HIV infection among adults (15–49 years) is estimated at 0.26%. The total number of people living with HIV (PLHIV) in India was estimated at 21.17 lakhs in 2015. There has been a declining trend in the mortality rate of HIV-infected patients on antiretroviral therapy (ART). With HIV becoming a chronic manageable disease, metabolic complications like diabetes mellitus (DM) and dyslipidemia are coming to the forefront. Generally, protease inhibitors (PI) are implicated in metabolic derangement; however, nucleoside reverse transcriptase inhibitors (NRTI) like stavudine can also cause diabetes. Among HIV-infected patients, the prevalence of diabetes is reported to range from 2 to 19%, so there is strong case for screening of diabetes among HIV-infected cases. The South Asian Consensus Guidelines recommend that both fasting and postprandial glucose values should be checked at screening and during monitoring of therapy. National AIDS Control Organization (NACO) recommends fasting plasma glucose with value ≥ 126 mg% diagnostic of diabetes mellitus. HbA1c may underestimate the degree of hyperglycemia in HIV-infected individuals and may not be a good diagnostic tool. Lifestyle modification is recommended as part of treatment. Metformin should be used with caution in HIV patients. Concomitant use of metformin with non-nucleoside reverse transcriptase inhibitors (NNRTI) can cause lactic acidosis. Thiazolidinediones should be the drug of choice in HIV, particularly in patients with lipodystrophy. Insulin secretagogues (meglitinides and sulfonylureas) are safe but may not be effective in the presence of severe insulin resistance. There are concerns regarding the use of gliptins in HIV-infected patients as they have molecular targets on immune cells. Insulin should be the drug of choice for HIV-infected patients with marked hyperglycemia (HbA1c > 9%), ketonuria, severe liver disease, or severe kidney disease. SGLT2 inhibitor may increase the risk of urinary tract infection and genital mycotic infections in HIV-infected diabetics. Regarding the use of ART among HIV patients with diabetes, NACO guidelines recommend that Tenofovir, lamivudine, and efavirenz should be used as first-line ART for all new patients, except known cases of severe diabetes, severe hypertension, or renal disease. Tenofovir, lamivudine, and lopinavir/ritonavir should be used as first line in women ever exposed to single dose Nevirapine in the past and also for all confirmed HIV-2 or HIV-1 & 2 coinfected patients. HIV infected with diabetes mellitus and microalbuminuria or proteinuria need Abacavir-based regimen (Abacavir + Lamivudine + Efavirenz). There is some suggestion that PI-based regimes should be avoided in patients at high risk of developing diabetes, for example, those with a history of gestational diabetes, positive family history of diabetes, or impaired glucose tolerance on screening.

scholarly journals Non-Nucleoside Reverse Transcriptase Inhibitors Join Forces with Integrase Inhibitors to Combat HIV

2020 ◽  
Vol 13 (6) ◽  
pp. 122
Author(s):  
Daniel M. Himmel ◽  
Eddy Arnold
Keyword(s):  
Reverse Transcriptase ◽  
Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Strand Transfer ◽  
Hiv Integrase ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Novel Treatments ◽  
Wide Range

In the treatment of acquired immune deficiency syndrome (AIDS), the diarylpyrimidine (DAPY) analogs etravirine (ETR) and rilpivirine (RPV) have been widely effective against human immunodeficiency virus (HIV) variants that are resistant to other non-nucleoside reverse transcriptase inhibitors (NNRTIs). With non-inferior or improved efficacy, better safety profiles, and lower doses or pill burdens than other NNRTIs in the clinic, combination therapies including either of these two drugs have led to higher adherence than other NNRTI-containing treatments. In a separate development, HIV integrase strand transfer inhibitors (INSTIs) have shown efficacy in treating AIDS, including raltegravir (RAL), elvitegravir (EVG), cabotegravir (CAB), bictegravir (BIC), and dolutegravir (DTG). Of these, DTG and BIC perform better against a wide range of resistance mutations than other INSTIs. Nevertheless, drug-resistant combinations of mutations have begun to emerge against all DAPYs and INSTIs, attributable in part to non-adherence. New dual therapies that may promote better adherence combine ETR or RPV with an INSTI and have been safer and non-inferior to more traditional triple-drug treatments. Long-acting dual- and triple-therapies combining ETR or RPV with INSTIs are under study and may further improve adherence. Here, highly resistant emergent mutations and efficacy data on these novel treatments are reviewed. Overall, ETR or RPV, in combination with INSTIs, may be treatments of choice as long-term maintenance therapies that optimize efficacy, adherence, and safety.

scholarly journals HIV-2: an overview

2015 ◽  
Vol 1 (1) ◽  
pp. 7
Author(s):  
Mangala S. Borkar ◽  
Akshay A. Kashid
Keyword(s):  
Reverse Transcriptase ◽  
Opportunistic Infections ◽  
Well Being ◽  
Response To Treatment ◽  
Strand Transfer ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Hiv 1

HIV-2 is much less common compared to HIV-1, has to be confirmed by HIV-2 Western Blot test and is resistant to Efavirinz and Nevirapine. There are two HIV viruses, HIV-1 and HIV-2. HIV-2 is relatively rare in India. The clinical course of HIV-2 infection is slower, plasma HIV-2 RNA levels are lower as compared to HIV-1 infection, but once the illness progresses to AIDS, the course is similar to HIV-1. In few cases, there may be mixed infection with both HIV-1 and HIV-2,but the course of the illness is like in HIV-1 However ,even in mixed infections, one has to give the therapy as we would in isolated HIV-2 infection. In general it is accepted that therapy in cases of HIV-2 infection should be started before there is clinical progression. Studies recommend starting therapy when CD4 count drops below 500. HIV-2 is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors. Therapy in HIV-2 patients should include two nucleoside reverse transcriptase inhibitors plus an HIV-2 active boosted protease inhibitor or integrase strand transfer inhibitors. Monitoring of CD4 cell counts and clinical improvement should be used to assess response to treatment. Drugs used in Government ART centres in India under the umbrella of NACO are Tenofovir 300mg + Lamivudine 300 mg + Lopinavir 200 mg + Ritonavir 50 mg and are observed to be beneficial clinically in terms of weight gain, increase in CD4 levels ,prevention and control of opportunistic infections and improved sense of well-being.

scholarly journals INSTIs and NNRTIs Potently Inhibit HIV-1 Polypurine Tract Mutants in a Single Round Infection Assay

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2501
Author(s):  
Steven J. Smith ◽  
Andrea Ferris ◽  
Xuezhi Zhao ◽  
Gary Pauly ◽  
Joel P. Schneider ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Envelope Gene ◽  
Strand Transfer ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Integrase Gene ◽  
Polypurine Tract ◽  
Emergence Of Resistance ◽  
Hiv 1

Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral compounds that prevent the insertion of a DNA copy of the viral genome into the host genome by targeting the viral enzyme integrase (IN). Dolutegravir (DTG) is a leading INSTI that is given, usually in combination with nucleoside reverse transcriptase inhibitors (NRTIs), to treat HIV-1 infections. The emergence of resistance to DTG and other leading INSTIs is rare. However, there are recent reports suggesting that drug resistance mutations can occur at positions outside the integrase gene either in the HIV-1 polypurine tract (PPT) or in the envelope gene (env). Here, we used single round infectivity assays to measure the antiviral potencies of several FDA-approved INSTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs) against a panel of HIV-1 PPT mutants. We also tested several of our promising INSTIs and NNRTIs in these assays. No measurable loss in potency was observed for either INSTIs or NNRTIs against the HIV-1 PPT mutants. This suggests that HIV-1 PPT mutants are not able, by themselves, to confer resistance to INSTIs or NNRTIs.

scholarly journals An insight on promising strategies hoping to cure HIV-1 infection by targeting Rev protein—short review

2021 ◽  
Author(s):  
Sahana Pai ◽  
Jayesh Mudgal ◽  
B. Venkatesh Kamath ◽  
K. Sreedhara Ranganath Pai
Keyword(s):  
Reverse Transcriptase ◽  
Regulatory Protein ◽  
Short Review ◽  
Fixed Dose ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Promising Therapeutic Target ◽  
Latent Hiv ◽  
Approved Drugs ◽  
Hiv 1

AbstractHuman immunodeficiency virus-1 (HIV-1) infection remains to be one of the major threats throughout the world. Many researchers are working in this area to find a cure for HIV-1. The group of the FDA approved drugs which are currently used against HIV-1 in the clinical practice include nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), integrase inhibitors (InIs), and protease inhibitors (PIs). Fixed dose combinations (FDCs) of these drugs are available and are used as per the anti-retroviral therapy (ART) guidelines. Despite these, unfortunately, there is no cure for HIV1 infection to date. The present review is focused upon describing the importance of a post-transcriptional regulatory protein “Rev”, responsible for latent HIV-1 infection as a possible, and promising therapeutic target against HIV-1.

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