The Continuous Surveillance of InSTI resistance could be an important Public Health Tool in the Fight against HIV Infection

2021 ◽  
Vol 19 ◽  
Author(s):  
Giuseppa Visalli ◽  
Alessio Facciolà ◽  
Maria Giovanna Costanzo ◽  
Angela Di Pietro
Keyword(s):  
Drug Resistance ◽  
Hiv Infection ◽  
Hiv Treatment ◽  
Large Cohort ◽  
University Hospital ◽  
Hiv Positive ◽  
Percentage Increase ◽  
Resistance Mutations ◽  
Hiv Test ◽  
Resistance Tests

Aims: To evaluate the frequency of the InSTIs mutations in a large cohort of HIV-infected people. Background: The Highly Active Anti-Retroviral Therapy (HAART) allow turning HIV infection from a fatal disease to a chronic infection and Integrase Strand Transfer Inhibitors (InSTIs) represent the cornerstone of this treatment. However, the spread of HIV-1 drug resistance mutations represents an emerging threat to the long-term success of HIV treatment programs. Objectives: To evaluate the trend of the HIV drug resistance to InSTIs in a large cohort of HIV-positive people in order to assess the risk represented by these subjects in the spread of the HIV infection to the community. Methods: A cross-sectional study was conducted analysing all the InSTIs resistance tests performed in HIV positive subjects in the period 2017-2019 by the HIV Laboratory of the University Hospital "Gaetano Martino" of Messina, Italy. Results: In 2017-2019, 252 InSTIs resistance tests were performed of which 59 (23.4%), 88 (34.9%) and 105 (41.7%) respectively in the three considered years. Overall, 28 (11.1%) samples showed resistance to at least one of the four InSTIs. We observed a significant percentage increase of 95% about the resistance to all the four drugs. Conclusion: Because the InSTI resistance is not rare, a continuous surveillance can represent nowadays, together with an incessant health education and a wide offer of the HIV test, the most important tool in the fight against HIV infection.

Behavioral and Clinical Characteristics and Outcomes of Treatment Among Older Patients Receiving Medical Care for HIV Infection in Iran

2021 ◽  
Author(s):  
Mehrnaz Rasoolinejad ◽  
Ali Asadollahi-Amin ◽  
Fateme Ghadimi ◽  
Masoudeh Mojahed ◽  
Omid Dadras ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Infection ◽  
Treatment Failure ◽  
Older Patients ◽  
Response To Treatment ◽  
Hiv Positive ◽  
Hiv Drug Resistance ◽  
Medical Comorbidities ◽  
Psychosocial Support System ◽  
Resistance Tests

Background: Although the number of new HIV infections continues to decline in Iran, the number of HIV-infected patients aged ≥50 years continues to rise due to the introduction of new treatment and longer survival. The higher prevalence of medical comorbidities and treatment failure in this population is a critical challenge in HIV treatment. In the present study, prevalence of comorbidities, rate of response to treatment, and results of HIV drug resistance tests were explored in older patients. Methods: A cross-sectional study was conducted at a tertiary referral HIV center in Tehran, Iran. The data for all the HIV-positive patients older than 50 years old were collected by reviewing their medical records within the last 15 years. Data included demographic and behavioral characteristics, immunologic and virologic response, rate of treatment failure, and HIV resistance. Results: The records for 100 patients with a mean age of 62.5 (range 50-79) years were reviewed and analyzed. Medical comorbidities were observed in 20% of the patients, with HCV co-infection, diabetes mellitus, and neuropsychiatric impairments being the most common. Complete immunologic and virologic responses were respectively observed in 88 and 97% of patients. The treatment regimen was modified in 66 patients, with drug side effects being the reason in 63 patients (95.4%). HIV drug resistance tests showed a low rate of resistance (<10%) to all drugs used in this population. Conclusion: Our findings highlight the high prevalence of comorbidities in older HIV-positive individuals in Iran. A thorough endocrine and neuropsychiatric assessment at each visit is recommended for these patients. Access to an appropriate psychosocial support system will ensure earlier detection of HIV infection and comorbidities in the older population, and will undoubtedly improve the treatment outcome and quality of life among them.

scholarly journals Analysis of Low-Frequency Mutations Associated with Drug Resistance to Raltegravir before Antiretroviral Treatment

2010 ◽  
Vol 55 (3) ◽  
pp. 1114-1119 ◽  
Author(s):  
Jia Liu ◽  
Michael D. Miller ◽  
Robert M. Danovich ◽  
Nathan Vandergrift ◽  
Fangping Cai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Failure ◽  
Low Frequency ◽  
Hiv Treatment ◽  
Viral Population ◽  
Virologic Suppression ◽  
Resistance Mutations ◽  
The Difference ◽  
Allele Specific Sequencing ◽  
Hiv 1

ABSTRACTRaltegravir is highly efficacious in the treatment of HIV-1 infection. The prevalence and impact on virologic outcome of low-frequency resistant mutations among HIV-1-infected patients not previously treated with raltegravir have not been fully established. Samples from HIV treatment-experienced patients entering a clinical trial of raltegravir treatment were analyzed using a parallel allele-specific sequencing (PASS) assay that assessed six primary and six secondary integrase mutations. Patients who achieved and sustained virologic suppression (success patients,n= 36) and those who experienced virologic rebound (failure patients,n= 35) were compared. Patients who experienced treatment failure had twice as many raltegravir-associated resistance mutations prior to initiating treatment as those who achieved sustained virologic success, but the difference was not statistically significant. The frequency of nearly all detected resistance mutations was less than 1% of viral population, and the frequencies of mutations between the success and failure groups were similar. Expansion of pre-existing mutations (one primary and five secondary) was observed in 16 treatment failure patients in whom minority resistant mutations were detected at baseline, suggesting that they might play a role in the development of drug resistance. Two or more mutations were found in 13 patients (18.3%), but multiple mutations were not present in any single viral genome by linkage analysis. Our study demonstrates that low-frequency primary RAL-resistant mutations were uncommon, while minority secondary RAL-resistant mutations were more frequently detected in patients naïve to raltegravir. Additional studies in larger populations are warranted to fully understand the clinical implications of these mutations.

scholarly journals Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhen Wang ◽  
Bin Zhao ◽  
Minghui An ◽  
Wei Song ◽  
Xue Dong ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Infection ◽  
Northeast China ◽  
Transmitted Drug Resistance ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Shenyang City ◽  
Subtype B ◽  
Recent Hiv Infection ◽  
Hiv 1

Abstract Background To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. Methods Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. Results A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). Conclusions The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.

Antimalarial drug resistance markers in human immunodeficiency virus (HIV)-positive and HIV-negative adults with asymptomatic malaria infections in Port Harcourt, Nigeria

2021 ◽  
Author(s):  
Ifeyinwa Chijioke-Nwauche ◽  
Mary C Oguike ◽  
Chijioke A Nwauche ◽  
Khalid B Beshir ◽  
Colin J Sutherland
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Drug Susceptibility ◽  
Blood Film ◽  
University Hospital ◽  
Hiv Positive ◽  
Asymptomatic Malaria ◽  
Immunodeficiency Virus ◽  
Before And After ◽  
Hiv Negative

Abstract Background In Nigeria, indiscriminate use of antimalarial drugs may contribute to the threat of drug resistance, but this has not been evaluated among people living with human immunodeficiency virus (HIV). Methods HIV-positive adults attending a university hospital HIV clinic and HIV-negative adult volunteers from the university hospital community with a positive blood film were treated with artemether–lumefantrine. Parasite DNA from before and after treatment was polymerase chain reaction amplified to identify molecular markers of drug susceptibility. Results The pfcrt76T genotype was prevalent among both HIV-positive and HIV-negative participants (78.6% and 68.2%, respectively). Three new mutations in the pfmdr1 gene—F73S, S97L and G165R—and the uncommon pfdhps S436F variant were detected, whereas pfdhps K540E and pfdhfr I164L were absent. The A437G allele of pfdhps predominated (62/66 [94%]). The I431 V mutation was found in 19 of 66 pretreatment pfdhps sequences (28.8%). The pfmdr1 86N allele was significantly more common at day 3 post-treatment than at baseline (odds ratio 8.77 [95% confidence interval 1.21 to 380]). Conclusions We found evidence of continued chloroquine use among HIV-positive individuals. Selection for the pfmdr1 86N after artemether–lumefantrine treatment was observed, indicating a possible threat to antimalarial efficacy in the study area. The complexity of pfdhps haplotypes emphasises the need for careful monitoring of anti-folate susceptibility in Nigeria.

scholarly journals Antiretroviral Resistance and Pregnancy Characteristics of Women with Perinatal and Nonperinatal HIV Infection

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Gweneth B. Lazenby ◽  
Okeoma Mmeje ◽  
Barbra M. Fisher ◽  
Adriana Weinberg ◽  
Erika K. Aaron ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Infection ◽  
Univariate Analysis ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Resistance Mutations ◽  
Hiv Drug Resistance ◽  
Fourfold Increase ◽  
Perinatal Hiv ◽  
Adverse Pregnancy

Objective. To compare HIV drug resistance in pregnant women with perinatal HIV (PHIV) and those with nonperinatal HIV (NPHIV) infection.Methods. We conducted a multisite cohort study of PHIV and NPHIV women from 2000 to 2014. Sample size was calculated to identify a fourfold increase in antiretroviral (ARV) drug resistance in PHIV women. Continuous variables were compared using Student’st-test and Wilcoxon rank-sum tests. Categorical variables were compared usingχ2and Fisher’s exact tests. Univariate analysis was used to determine factors associated with antiretroviral drug resistance.Results. Forty-one PHIV and 41 NPHIV participants were included. Women with PHIV were more likely to have drug resistance than those with NPHIV ((55% versus 17%,p=0.03), OR 6.0 (95% CI 1.0–34.8),p=0.05), including multiclass resistance (15% versus 0,p=0.03), and they were more likely to receive nonstandard ARVs during pregnancy (27% versus 5%,p=0.01). PHIV and NPHIV women had similar rates of preterm birth (11% versus 28%,p=0.08) and cesarean delivery (47% versus 46%,p=0.9). Two infants born to a single NPHIV woman acquired HIV infection.Conclusions. PHIV women have a high frequency of HIV drug resistance mutations, leading to nonstandard ARVs use during pregnancy. Despite nonstandard ARV use during pregnancy, PHIV women did not experience increased rates of adverse pregnancy outcomes.

scholarly journals More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Alison F Feder ◽  
Soo-Yon Rhee ◽  
Susan P Holmes ◽  
Robert W Shafer ◽  
Dmitri A Petrov ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Treatment ◽  
Adaptive Mutation ◽  
Selective Sweeps ◽  
Resistance Mutations ◽  
Consensus Sequences ◽  
Adaptive Mutations ◽  
Slow Evolution ◽  
Effective Drugs ◽  
Hiv 1

In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here, we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.

scholarly journals Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya

2020 ◽  
Vol 30 (1) ◽  
Author(s):  
Mabeya Sepha ◽  
Nyamache Anthony ◽  
Ngugi Caroline ◽  
Nyerere Andrew ◽  
Lihana Raphael
Keyword(s):  
Drug Resistance ◽  
Direct Sequencing ◽  
Integrase Inhibitor ◽  
Hiv Treatment ◽  
Strand Transfer ◽  
Hiv Integrase ◽  
Integrase Inhibitors ◽  
Resistance Mutations ◽  
Integrase Gene ◽  
Hiv 1

BACKGROUND: Antiretroviral therapy containing an integrase strand transfer inhibitor plus two Nucleoside Reverse Transcriptase inhibitors has now been recommended for treatment of HIV-1-infected patients. This thus determined possible pre-existing integrase resistance associated mutations in the integrase gene prior to introduction of integrase inhibitors combination therapy in Kenya.METHODS: Drug experienced HIV patients were enrolled at Kisii Teaching and Referral in Kenya. Blood specimens from (33) patients were collected for direct sequencing of HIV-1 polintegrase genes. Drug resistance mutations were interpreted according to the Stanford algorithm and phylogenetically analysed using insilico tools.RESULTS: From pooled 188 Kenyan HIV integrase sequences that were analysed for drug resistance, no major mutations conferring resistance to integrase inhibitors were detected. However, polymorphic accessory mutations associated with reduced susceptibility of integrase inhibitors were observed in low frequency; M50I (12.2%), T97A (3.7%), S153YG, E92G (1.6%), G140S/A/C (1.1%) and E157Q (0.5%). Phylogenetic analysis (330 sequences revealed that HIV-1 subtype A1 accounted for majority of the infections, 26 (78.8%), followed by D, 5 (15.2%) and C, 2 (6%).CONCLUSION: The integrase inhibitors will be effective in Kenya where HIV-1 subtype A1 is still the most predominant. However, occurring polymorphisms may warrant further investigation among drug experienced individuals on dolutegravir combination or integrase inhibitor treatment. 

Pre-treatment and acquired HIV drug resistance in Dar es Salaam, Tanzania in the era of tenofovir and routine viral load monitoring

2019 ◽  
Vol 74 (10) ◽  
pp. 3016-3020 ◽  
Author(s):  
Godfrey Barabona ◽  
Macdonald Mahiti ◽  
Salim Masoud ◽  
Peter Mbelele ◽  
Amina Shaban Mgunya ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Progressive Increase ◽  
Dar Es Salaam ◽  
Antiretroviral Drugs ◽  
Hiv Treatment ◽  
Resistance Mutations ◽  
Genetic Barrier ◽  
Hiv Drug Resistance ◽  
Pre Treatment ◽  
Treat All

Abstract Objectives We investigated the prevalence and patterns of pre-treatment and acquired HIV drug resistance mutations (DRMs) in Tanzania as a ‘treat all’ strategy, virological monitoring and the progressive increase in usage of tenofovir are being implemented in HIV treatment programmes. Methods Viral RNA was isolated from plasma of 60 ART-naive and 166 treated-but-viraemic (>400 copies/mL) HIV-1-infected adults attending a care and treatment clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania, between June and October 2017. Viral genes encoding protease and reverse transcriptase were amplified by PCR and directly sequenced. Results Viral genotyping of successfully amplified samples revealed pre-treatment DRMs in 14/47 (29.8%) ART-naive subjects. Of these, 7/47 (14.9%) harboured mutations that confer high-level resistance to at least one drug of the default first-line regimen. In treated-but-viraemic subjects, DRMs were found in 100/111 (90%), where DRMs against NNRTI, NRTI and PI were observed in 95/100 (95%), 92/100 (92%) and 13/100 (13%), respectively. Tenofovir-resistance mutations K65R and K70G/E or ≥3 thymidine analogue resistance mutations including M41L and L210W were found in 18/36 (50%) subjects on a tenofovir-containing regimen at failure. Four patients harboured multiple DRMs, which can confer resistance to all available ART regimens in Tanzania. Conclusions Taken together, pre-treatment and acquired DRMs were highly prevalent, which represents a major risk for the efficacy of ART programmes in Tanzania. Availability of a newer generation of antiretroviral drugs with a higher genetic barrier to resistance and robust treatment monitoring is warranted for effective and sustainable HIV treatment.

scholarly journals Primary HCV Drug Resistance Mutations in Patients with Newly Diagnosed HIV Infection

2020 ◽  
pp. 97-105
Author(s):  
Yu. V. Ostankova ◽  
D. E. Valutite ◽  
E. B. Zueva ◽  
E. N. Serikova ◽  
A. N. Shchemelev ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Infection ◽  
Hcv Rna ◽  
Laboratory Diagnostics ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Primary Drug Resistance ◽  
Two Samples ◽  
Significant Difference

Objective of our work was to assess prevalence of the primary HCV drug resistance mutations in the NS5b gene in patients with newly diagnosed HIV infection.Materials and methods. The study material was 196 blood plasma samples from patients living in the North-Western Federal District with newly diagnosed HIV. Samples were examined for the anti-HCV antibodies and HCV RNA presence. If HCV RNA was detected, amplification was performed using three primers pairs that co-flanked the NS5b gene. After sequencing the indicated gene nucleotide sequence, the virus subtype was determined and drug resistance mutations were detected.Results and discussion. Antibodies to HCV were detected in 18.87 % of HIV-infected individuals. HCV RNA was detected in 18.36 % of the patients, including 89.18 % anti-HCV-positive and 1.88 % anti-HCV-negative. It was shown that co-infection is more common in men (77.8 %) compared to women (22.2 %) – χ2 = 3.996 at p = 0.0456, df = 2. The difference in the HIV viral load between the groups with HIV monoinfection and with HIV + HCV coinfection was demonstrated (χ2 = 6.284 at p = 0.0432, df = 2). A significant difference between the groups by the CD4 + lyphocytes number was shown. In the phylogenetic analysis, the HCV subtypes are distributed as follows: HCV 1b – 47.2 %, HCV 3a – 30.6 %, HCV 1a – 13.9 %, HCV 2a – 5.5 % and only one sample was defined as HCV 2k – 2.8 %, respectively. Nine samples (25 %) presented NS5b mutations in  the positions related to the development of drug resistance of HCV, including two samples among HCV genotypes 1a and 3a (i.e., 5.6 % of the total HIV + HCV group), as well as five samples among HCV 1b (13.9 % of the total group). Mutations among HCV 1a were C316Y and N444D substitutions. Among HCV 1b, C316N, C451S, S556N/G substitutions were identified. Among patients with HCV 3a, 2 samples (5.6 %) with a D310N mutation associated with an unfavorable disease prognosis were found. The introduction of direct sequencing of HCV nucleotide sequences into the routine laboratory diagnostics will allow us to estimate the primary drug resistance mutations prevalence in risk groups to predict the HCV life-threatening complications development – fibrosis, cirrhosis, hepatocellular carcinoma, as well as the outcome of antiviral therapy prognosis. The data obtained can be rationally used to assess the dynamics of the HCV primary pharmacoresistance prevalence among HIV-infected individuals.

scholarly journals Stochastic investigation of HIV infection and the emergence of drug resistance

2021 ◽  
Vol 19 (2) ◽  
pp. 1174-1194
Author(s):  
Damilola Olabode ◽  
◽  
Libin Rong ◽  
Xueying Wang ◽  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Stochastic Models ◽  
Early Stage ◽  
Critical Role ◽  
Resistance Mutations ◽  
Multitype Branching Process ◽  
Increased Risk ◽  
Hiv 1

<abstract><p>Drug-resistant HIV-1 has caused a growing concern in clinic and public health. Although combination antiretroviral therapy can contribute massively to the suppression of viral loads in patients with HIV-1, it cannot lead to viral eradication. Continuing viral replication during sub-optimal therapy (due to poor adherence or other reasons) may lead to the accumulation of drug resistance mutations, resulting in an increased risk of disease progression. Many studies also suggest that events occurring during the early stage of HIV-1 infection (i.e., the first few hours to days following HIV exposure) may determine whether the infection can be successfully established. However, the numbers of infected cells and viruses during the early stage are extremely low and stochasticity may play a critical role in dictating the fate of infection. In this paper, we use stochastic models to investigate viral infection and the emergence of drug resistance of HIV-1. The stochastic model is formulated by a continuous-time Markov chain (CTMC), which is derived based on an ordinary differential equation model proposed by Kitayimbwa et al. that includes both forward and backward mutations. An analytic estimate of the probability of the clearance of HIV infection of the CTMC model near the infection-free equilibrium is obtained by a multitype branching process approximation. The analytical predictions are validated by numerical simulations. Unlike the deterministic dynamics where the basic reproduction number $ \mathcal{R}_0 $ serves as a sharp threshold parameter (i.e., the disease dies out if $ \mathcal{R}_0 &lt; 1 $ and persists if $ \mathcal{R}_0 &gt; 1 $), the stochastic models indicate that there is always a positive probability for HIV infection to be eradicated in patients. In the presence of antiretroviral therapy, our results show that the chance of clearance of the infection tends to increase although drug resistance is likely to emerge.</p></abstract>

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