scholarly journals Human Immunodeficiency Virus (HIV) Drug Resistance: A Global Narrative Review

2021 ◽  
Vol 2 (9) ◽  
pp. 857-864
Author(s):  
Maureen Nkandu Phiri ◽  
Steward Mudenda
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Therapy Resistance ◽  
Narrative Review ◽  
Hiv Vaccines ◽  
Genetic Barrier ◽  
Hiv Drug Resistance ◽  
Immunodeficiency Virus

Background: Antiretroviral Therapy (ART) has significantly improved Human Immunodeficiency Virus (HIV) patients’ survival rates. However, the emergence of HIV Drug Resistance (HIVDR) has markedly reduced the effectiveness of Antiretroviral Therapy (ART). Aim: This narrative review was conducted to review published studies on HIV drug resistance and its consequences. Materials and methods: A literature search for this narrative review was carried out and the following databases were used PubMed, Google Scholar, and The Lancet. The cited articles were published from 1999 to 2021. The keywords used in the search of literature included ‘Antiretroviral therapy’, ‘resistance’, and ‘Human Immunodeficiency Virus drug resistance’, ‘HIV’, ‘HIV drug resistance’, ‘HIV vaccines’, and the Boolean word ‘AND’. Results: There is a high prevalence of HIV drug resistance globally that has been associated with some factors such as older age, non-adherence to treatment, long treatment duration, lower cell count and high viral load. HIV drug resistance may lead to treatment failure, prolongation of the time required to achieve viral suppression and leads to increased mortality. Increasing access to viral load monitoring can help mitigate HIV drug resistance. Conclusion: HIV drug resistance is a global threat to public health and has been associated with increased morbidity and mortality. Therefore, there is a need for more research to be carried out and various strategies like the use of antiretrovirals with a high genetic barrier to resistance need to be put in place to prevent further spread resistance. HIVDR must be monitored frequently taking into consideration the geographic variability. There is an urgent need for the development of anti-HIV vaccines that will help to prevent further transmission and spread of HIV.

scholarly journals Association between Adherence to Antiretroviral Therapy and Human Immunodeficiency Virus Drug Resistance

2003 ◽  
Vol 37 (8) ◽  
pp. 1112-1118 ◽  
Author(s):  
A. K. Sethi ◽  
D. D. Celentano ◽  
S. J. Gange ◽  
R. D. Moore ◽  
J. E. Gallant
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Immunodeficiency Virus

scholarly journals Cryptococcal Antigenemia in Human Immunodeficiency Virus Antiretroviral Therapy–Experienced Ugandans With Virologic Failure

2019 ◽  
Vol 71 (7) ◽  
pp. 1726-1731 ◽  
Author(s):  
Edward Mpoza ◽  
Radha Rajasingham ◽  
Lillian Tugume ◽  
Joshua Rhein ◽  
Maria Sarah Nabaggala ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Cryptococcal Meningitis ◽  
Virologic Failure ◽  
Cost Effective ◽  
World Health ◽  
Load Testing ◽  
Viral Loads ◽  
Immunodeficiency Virus

Abstract Background Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus–positive persons with CD4 count <100 cells/μL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown. Methods We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017–January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review. Results Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10–84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8–19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads <5000 copies/mL. Conclusions In addition to the CD4 threshold of <100 cells/μL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL.

scholarly journals Plasmodium falciparum Infection Does Not Affect Human Immunodeficiency Virus Viral Load in Coinfected Rwandan Adults

2014 ◽  
Vol 1 (2) ◽  
Author(s):  
Krishanthi Subramaniam ◽  
Rebeca M. Plank ◽  
Nina Lin ◽  
Adam Goldman-Yassen ◽  
Emil Ivan ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Viral Load ◽  
Malaria Infection ◽  
Hiv Transmission ◽  
Falciparum Infection ◽  
Resistance Testing ◽  
Plasmodium Falciparum Infection ◽  
Immunodeficiency Virus

Abstract Background.  Plasmodium falciparum infection has been reported to increase human immunodeficiency virus (HIV) viral load (VL), which can facilitate HIV transmission. We prospectively studied the impact of mild P falciparum coinfection on HIV VL in Rwanda. Methods.  We measured plasma HIV VL at presentation with malaria infection and weekly for 4 weeks after artemether-lumefantrine treatment in Rwandan adults infected with HIV with P falciparum malaria. Regression analyses were used to examine associations between malaria infection and HIV VL changes. Samples with detectable virus underwent genotypic drug-resistance testing. Results.  We enrolled 28 HIV-malaria coinfected patients and observed 27 of them for 5 weeks. Three patients (11%) were newly diagnosed with HIV. Acute P falciparum infection had no significant effect on HIV VL slope over 28 days of follow-up. Ten patients with VL <40 copies/mL at enrollment maintained viral suppression throughout. Seventeen patients had a detectable VL at enrollment including 9 (53%) who reported 100% adherence to ARVs; 3 of these had detectable genotypic drug resistance. Conclusions.  Unlike studies from highly malaria-endemic areas, we did not identify an effect of P falciparum infection on HIV VL; therefore, malaria is not likely to increase HIV-transmission risk in our setting. However, routine HIV testing should be offered to adults presenting with acute malaria in Rwanda. Most importantly, we identified a large percentage of patients with detectable HIV VL despite antiretroviral (ARV) therapy. Some of these patients had HIV genotypic drug resistance. Larger studies are needed to define the prevalence and factors associated with detectable HIV VL in patients prescribed ARVs in Rwanda.

scholarly journals Discrepancies between Protease Inhibitor Concentrations and Viral Load in Reservoirs and Sanctuary Sites in Human Immunodeficiency Virus-Infected Patients

2003 ◽  
Vol 47 (1) ◽  
pp. 238-243 ◽  
Author(s):  
Caroline Solas ◽  
Alain Lafeuillade ◽  
Philippe Halfon ◽  
Stéphane Chadapaud ◽  
Gilles Hittinger ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Lymph Node ◽  
Viral Load ◽  
Lymphoid Tissue ◽  
Drug Penetration ◽  
Hiv Rna ◽  
Drug Concentrations ◽  
Immunodeficiency Virus ◽  
Rna Levels

ABSTRACT The variable penetration of antiretroviral drugs into sanctuary sites may contribute to the differential evolution of human immunodeficiency virus (HIV) and the emergence of drug resistance. We evaluated the penetration of indinavir, nelfinavir, and lopinavir-ritonavir (lopinavir/r) in the central nervous system, genital tract, and lymphoid tissue and assessed the correlation with residual viral replication. Plasma, cerebrospinal fluid (CSF), semen, and lymph node biopsy samples were collected from 41 HIV-infected patients on stable highly active antiretroviral therapy regimens to determine drug concentrations and HIV RNA levels. When HIV RNA was detectable, sequencing of the reverse transcriptase and protease genes was performed. Ratios of the concentration in semen/concentration in plasma were 1.9 for indinavir, 0.08 for nelfinavir, and 0.07 for lopinavir. Only indinavir was detectable in CSF, with a concentration in CSF/concentration in plasma ratio of 0.17. Differential penetration into lymphoid tissue was observed, with concentration in lymph node tissue/concentration in plasma ratios of 2.07, 0.58, and 0.21 for indinavir, nelfinavir, and lopinavir, respectively. HIV RNA levels were <50 copies/ml in all CSF samples of patients in whom HIV RNA was not detectable in plasma. HIV RNA was detectable in the semen of three patients (two patients receiving nelfinavir and one patient receiving lopinavir/r), and its detection was associated with multiple resistance mutations, while the viral load in plasma was undetectable. HIV RNA was detectable in all lymph node tissue samples. Differential drug penetration was observed among the three protease inhibitors in the sanctuary sites, but there was no correlation between drug levels and HIV RNA levels, suggesting that multiple factors are involved in the persistence of viral reservoirs. Further studies are required to clarify the role and clinical relevance of drug penetration in sanctuaries in terms of long-term efficacy and drug resistance.

scholarly journals Decreased Bone Formative and Enhanced Resorptive Markers in Human Immunodeficiency Virus Infection: Indication of Normalization of the Bone-Remodeling Process during Highly Active Antiretroviral Therapy1

1999 ◽  
Vol 84 (1) ◽  
pp. 145-150 ◽  
Author(s):  
Pål Aukrust ◽  
Charlotte J. Haug ◽  
Thor Ueland ◽  
Egil Lien ◽  
Fredrik Müller ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Bone Formation ◽  
Bone Remodeling ◽  
Highly Active Antiretroviral Therapy ◽  
Serum Concentrations ◽  
Marked Rise ◽  
Highly Active ◽  
Immunodeficiency Virus

As cytokines and 1,25-dihydroxyvitamin D [1,25-(OH)2D] appear to have an important role in bone homeostasis, we examined the possibility that human immunodeficiency virus (HIV)-infected patients, characterized by enhanced levels of proinflammatory cytokines and 1,25-(OH)2D deficiency, have disturbed bone metabolism by analyzing serum markers of bone formation (osteocalcin) and bone resorption (C-telopeptide) in 73 HIV-infected patients. HIV-infected patients with advanced clinical and immunological disease and high viral load were characterized by increased C-telopeptide and particularly by markedly depressed osteocalcin levels. HIV-infected patients had enhanced activation of the TNF system. Serum concentrations of p55 and p75-TNF receptors were negatively correlated with osteocalcin, and p75-TNF receptor was positively correlated with C-telopeptide. HIV-infected patients with advanced disease also had decreased serum concentrations of 1,25-(OH)2D, but this parameter was not correlated with osteocalcin or C-telopeptide. During 24 months with highly active antiretroviral therapy there was a marked rise in serum osteolcalcin levels together with a profound fall in viral load and TNF components and a marked rise in CD4+ T cell counts. Also, there was a shift from no correlation to a significant correlation between osteocalcin and C-telopeptide levels during such therapy. The present study suggests disturbed bone formation and resorption during HIV infection. Our findings indicating synchronization of bone remodeling during highly active antiretroviral therapy may represent a previously unrecognized beneficial effect of such therapy and expand our knowledge of the interactions between cytokines and bone in the bone-remodeling process.

scholarly journals Screening for antiretroviral drug resistance among treatment-naive human immunodeficiency virus type 1-infected individuals in Lebanon

2014 ◽  
Vol 8 (03) ◽  
pp. 339-348
Author(s):  
Jacques M Mokhbat ◽  
Nada M. Melhem ◽  
Ziad El-Khatib ◽  
Pierre Zalloua
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Viral Load ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Newly Diagnosed ◽  
Reverse Transcriptase Inhibitors ◽  
Immunodeficiency Virus ◽  
Hiv 1

Introduction: Antiretroviral therapy (ART) has been successful at decreasing the morbidity and mortality associated with human immunodeficiency virus type 1 (HIV-1) infection. HIV-1 drug resistance (HIVDR) among ART-naive patients has been documented to compromise the success of initial therapy. This study was conducted to determine the prevalence of HIVDR mutations among newly diagnosed drug-naive HIV-infected individuals in Lebanon. Methodology: Plasma samples from 37 newly diagnosed participants at various stages of HIV-1 infection were used to determine HIV-1 RNA viral load, isolate viral RNA, and amplify DNA by RT-PCR. Purified PCR products were used to perform genotypic resistance tests. Results: The prevalence of resistance mutations to nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRT), and protease inhibitors (PI) were 5.4%, 10.8%, and 8%, respectively. The major mutations detected in the study participants conferred resistance to NRTIs and NNRTIs recommended for HIV-1 treatment.  No significant relationship between HIV-1 viral load of participants and the mode of HIV-1 transmission or between the occurrence of HIVDR and the mode of transmission was found. Conclusions: To our knowledge, this is the first study on HIVDR mutations among newly diagnosed HIV-infected persons in Lebanon. The overall prevalence of HIVDR mutations detected in our study was 16%. Our results are important for evaluating the utility of the standard first-line regimens in use, determining the feasibility of HIVDR testing before the initiation of ART, as well as minimizing the emergence and transmission of HIVDR.

scholarly journals Expansion of Viral Load Testing and the Potential Impact on Human Immunodeficiency Virus Drug Resistance

2017 ◽  
Vol 216 (suppl_9) ◽  
pp. S808-S811 ◽  
Author(s):  
Helen M Chun ◽  
Yaa F Obeng-Aduasare ◽  
Laura N Broyles ◽  
Dennis Ellenberger
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Viral Load ◽  
Load Testing ◽  
Viral Load Testing ◽  
Immunodeficiency Virus ◽  
Potential Impact
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