HIV Drug Resistance Research Articles

A validated in-house assay for HIV drug resistance mutation surveillance from dried blood spot specimens

Despite increasing scale-up of antiretroviral therapy (ART) coverage, challenges related to adherence and HIV drug resistance (HIVDR) remain. The high cost of HIVDR surveillance is a persistent challenge with implementation in resource-constrained settings. Dried blood spot (DBS) specimens have been demonstrated to be a feasible alternative to plasma or serum for HIVDR genotyping and are more suitable for lower resource settings. There is a need for affordable HIVDR genotyping assays which can amplify HIV-1 sequences from DBS specimens, particularly those with low viral loads, at a low cost. Here, we present an in-house assay capable of reliably amplifying HIV-1 protease and partial reverse transcriptase genes from DBS specimens, which covers the complete World Health Organization 2009 list of drug resistance mutations under surveillance. DBS specimens were prepared using whole blood spiked with HIV-1 at concentrations of 10,000, 5000, 1000, and 500 copies/mL (n=30 for each concentration). Specimens were tested in triplicate. A two-step approach was used consisting of cDNA synthesis followed by nested PCR. The limit of detection of the assay was calculated to be approximately 5000 (95% CI: 3200–10,700) copies/mL for the protease gene and 3600 (95% CI: 2200–10,000) copies/mL for reverse transcriptase. The assay was observed to be most sensitive with higher viral load specimens (97.8% [95% CI: 92.2–99.7]) for both protease and reverse transcriptase at 10,000 copies/mL with performance decreasing with the use of specimens with lower viral loads (46.7% [36.1–57.5] and 60.0% [49.1–70.2] at 500 copies/mL for protease and reverse transcriptase, respectively). Ultimately, this assay presents a promising opportunity for use in resource-constrained settings. Future work should involve validation under field conditions including sub-optimal storage conditions and preparation of DBS with fingerprick blood in order to accurately reflect real-world collection scenarios.

Emergence of HIV-1 drug resistance mutations among children and adolescents undergoing prolonged antiretroviral therapy in Guangxi

Antiretroviral therapy (ART) has been implemented in Guangxi for a long time, and there are no reports of HIV drug resistance mutation (DRM) among children and adolescents experiencing virologic failure after ART. This study aimed to analyse HIV DRM prevalence, patterns, and influencing factors among children and adolescents experiencing virologic failure after ART in Guangxi. We collected samples from a total of 491 HIV-infected individuals under 18 years old experiencing virologic failure after ART from 14 cities in Guangxi. Sequencing and DRM analysis were performed based on pol region. Multivariate logistic regression was employed to analysis the influencing factors of DRM. Among these patients, 396 cases were successfully sequenced. Of all, 52.53% exhibited HIV DRM, including NNRTI (48.48%), NRTI (34.85%) and PI (1.01%). NRTI and NNRTI dual-class resistance was prevalent (30.3%). M184V/I and K103N mutations were the common mutations in NRTI and NNRTI, respectively. Male sex (aOR = 2.1, 95% CI: 1.26-3.50), CRF01_AE subtype (OR = 2.50, 95% CI: 1.02-5.88), the primary regimen 3TC+AZT+NVP (OR = 10.00, 95% CI: 5.00-25.00), low pretreatment CD4+ T lymphocytes (<200 cells/mm³) (OR = 1.85, 95% CI: 1.00-3.45), and high viral load (>1000 copies/mL) (OR = 4.90, 95% CI: 1.03-23.39) showed higher risk of DRM. HIV DRM is pervasive among children and adolescents experiencing virologic failure in Guangxi. Timely HIV DRM monitoring is crucial to mitigate major mutation accumulation and inform effective treatment strategies.

Pretreatment HIV-1 Resistance in Argentina: Results from the Second Surveillance Study Following World Health Organization Guidelines (2019).

More than 62,000 individuals are currently on antiretroviral treatment within the public health system in Argentina. In 2019, more than 50% of people on ART received non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this context, the second nationwide HIV-1 pretreatment drug resistance surveillance study was carried out between April and December 2019 to assess the prevalence of HIV-1 drug resistance in Argentina using the World Health Organization guidelines. This was a nationwide cross-sectional study enrolling consecutive 18-year-old and older individuals starting ARVs at 19 ART-dispensing centers. This allowed us to estimate a point prevalence rate of resistance-associated mutations (RAMs) with a confidence interval (CI) of 5% (for the total population and for those without antiretroviral exposure). Four-hundred forty-seven individuals were included in the study. The prevalence of mutations associated with resistance was detected in 27.7% (95% CI 25.6-34.9%) of the population. For NNRTI, it was 19.6% (95% CI 16.3-24.5%), for integrase strand transfer inhibitor (INSTI) 6.1% (95% CI 6.1-11.9%), for nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) 3% (95% CI 1.9-5.9%), and for protease inhibitors 1.5% (95% CI 0.7-3.6%). Naive individuals had variants of resistance to NRTIs in 16.8% (95% CI 12.8-21.4) and 5.7% (95% CI 2.9-15.9) to INSTI. For experienced individuals, the prevalence of variants associated with resistance was 30.38% (95% CI 20.8-42.2) for NRTIs and 7.7% (95% CI 2.9-15.9) for INSTI. This study shows an increase in the frequency of nonpolymorphic RAMs associated with resistance to NNRTI. This study generates the framework of evidence that supports the use of schemes based on high genetic barrier integrase inhibitors as the first line of treatment and the need for the use of resistance test before prescribing schemes based on NNRTI. We report for the first time the presence of a natural polymorphism associated with the most prevalent recombinant viral form in Argentina and the presence of a mutation linked to first-line integrase inhibitors such as raltegravir.

Prevalence of HIV Drug Resistance Mutations among Treatment-Naive People Living with HIV in a Tertiary Care Center in India.

India has the third-largest number of people living with HIV (PLHIV) in the world. A national program provides free access to standard uniform antiretroviral therapy. However, the program is not monitored by comprehensive drug resistance surveys. The aim of this study was to determine the prevalence of HIV drug resistance mutations (DRMs) among treatment-naive PLHIV in a large antiretroviral treatment center of the national program. This cross-sectional study was done in 2017 and involved 200 consecutive treatment-naive PLHIV. A target fragment of 1,306 bp in the reverse transcriptase and protease regions was amplified. Identification of mutations and drug resistance interpretation was done by HIV Genotypic Resistance Interpretation and International Antiviral Society-USA list. Sequencing was successful in 177 samples. The majority (98.8%; 175/177) belonged to subtype C. Nineteen of 177 patients (10.7%; 95% CI: 6.2%-15.3%) had at least one major DRM. The prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations was 10.2% (18/177). The most frequent mutations were E138A/K, A98G, K103N, V179D, and K101H/E. The prevalence of nucleoside reverse transcriptase inhibitor (NRTI) mutations was 1.1% (2/177). None of the samples had major protease inhibitor resistance mutations. The prevalence of NNRTI mutations in this study was >10%, crossing the threshold recommended by the WHO to change the NNRTI-based first-line regimen to non-NNRTI based. In 2021, the national program replaced efavirenz with dolutegravir in the first-line regimen of tenofovir, lamivudine, and efavirenz. As the majority (64%) of PLHIV in India are accessing free ART from the national program, this study highlights the need for regular nationally representative drug resistance surveys for optimizing antiretroviral regimens in the program.

Exact selective inference with randomization

Summary We introduce a pivot for exact selective inference with randomization. Not only does our pivot lead to exact inference in Gaussian regression models, but it is also available in closed form. We reduce this problem to inference for a bivariate truncated Gaussian variable. By doing so, we give up some power that is achieved with approximate maximum likelihood estimation in Panigrahi &amp; Taylor (2023). Yet our pivot always produces narrower confidence intervals than a closely related data-splitting procedure. We investigate the trade-off between power and exact selective inference on simulated datasets and an HIV drug resistance dataset.

Real-World Effectiveness of Dolutegravir/Lamivudine in People With HIV-1 in Test-and-Treat Settings or With High Baseline Viral Loads: TANDEM Study Subgroup Analyses.

Dolutegravir/lamivudine (DTG/3TC) was first approved by the US Food and Drug Administration in 2019 for the treatment of antiretroviral therapy (ART)-naive people with HIV-1 based on results from the pivotal GEMINI-1/GEMINI-2 trials. Around that time, immediate initiation of treatment upon diagnosis was recommended in the US Department of Health and Human Services guidelines. Here we report results from 126 treatment-naive people with HIV-1 who initiated DTG/3TC as part of a test-and-treat strategy (n = 61) or with high baseline viral loads (HIV-1 RNA ≥ 100,000 copies/ml; n = 16) from the TANDEM study. TANDEM was a US-based, retrospective chart review study that included a cohort of 126 individuals aged ≥ 18years with no prior history of ART who initiated DTG/3TC before September 30, 2020, and had ≥ 6months of follow-up. Test-and-treat was defined as ART initiation shortly after diagnosis without available viral load, CD4 + cell count, or HIV-1 resistance data. Outcomes included virologic suppression (HIV-1 RNA < 50 copies/ml; overall and by baseline viral load) and discontinuations. Analyses were descriptive. Among 61 individuals who initiated DTG/3TC in a test-and-treat setting (median [interquartile range (IQR)] treatment duration, 1.3 [0.9-1.7] years), 57 (93%) achieved virologic suppression, and 51 (84%) remained suppressed; 1 (< 1%) individual discontinued DTG/3TC due to persistent low-level viremia. The most common healthcare provider (HCP)-reported reason for initiating DTG/3TC was avoidance of long-term toxicities among individuals in the test-and-treat subgroup. Of 16 treatment-naive individuals with high baseline viral loads (median [IQR] treatment duration, 100,000-250,000 copies/ml: 1.2 [0.8-1.8] years; > 250,000 copies/ml: 1.0 [0.7-1.1] years), 14 (88%) achieved virologic suppression, 13 (81%) remained suppressed, and none discontinued DTG/3TC. Patient preference was the most common HCP-reported reason for initiating DTG/3TC in this subgroup. Results demonstrate real-world effectiveness of DTG/3TC, with few discontinuations, in people with HIV-1 in test-and-treat settings or with high baseline viral loads.

A systematic review and meta-analysis of HIV transmission risk behaviors, genetic variations, and antiretroviral (ARV) resistance in LGBT populations.

Currently, human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) has become one of the major health problems worldwide, including Indonesia. East Java is one of the provinces in Indonesia with the highest prevalence of HIV infection. One of the causes of HIV infection transmission is lesbian, gay, bisexual, and transgender (LGBT) practice. Furthermore, the treatment using antiretroviral (ARV) drugs in HIV-1 patients can fail due to the presence of HIV drug resistance. The aim of this study is to identify the behavior at risk of HIV transmission among LGBT, patterns of genetic variation and antiretroviral (ARV) resistance. A systematic review and meta-analysis based on the PRISMA guidelines was conducted. We searched three databases including PubMed, ScienceDirect, and Google scholar for studies investigating the non-heterosexual behavior as risk factor of HIV infection and antiretroviral resistance. Only studies published in English are considered. The adjusted estimates of the risk were carried out using best-adjusted OR with 95% confidence interval (CI) and significant p value < 0.05. In the quantitative analysis of HIV infection risk factors, a total of 13 studies were included, which investigated non-heterosexual behavior as a potential factor. The studies involved a total of 37,129 participants, comprising 10,449 individuals in the non-heterosexual behavior group (LGBTQ+) and 26,680 individuals in the heterosexual group. The majority of the participants in this study were from the USA, Japan, China, and Brazil, and the main HIV subgenotypes were B and CRF. Additionally, the antiretroviral resistance of HIV patients was examined, involving a total of 3062 individuals, with 1296 individuals in the non-heterosexual behavior group and 1766 individuals in the heterosexual group. Our calculation showed that non-heterosexual behavior was significant as risk factor of HIV infection (OR = 2.17, 95% CI = 1.94-2.43, p < 0.001) and antiretroviral resistance (OR = 1.31, 95% CI = 1.00-1.71, p = 0.05). This study concludes that non heterosexual behavior is significant risk factor of HIV infection. A quite prevalent of antiretroviral resistance were found among non heterosexual behavior. The main subgenotype of HIV are B and CRF.

Optimising HIV drug resistance testing laboratory networks in Kenya: insights from systems engineering modelling

BackgroundHIV drug resistance (DR) is a growing threat to the durability of current and future HIV treatment success. DR testing (DRT) technologies are very expensive and specialised, relying on centralised...

Adherence of HIV/AIDS patients to clinical outcome in Semarang City

Background: The success of HIV therapy can be measured by clinical, immunological, and virological monitoring. Meanwhile, low adherence to antiretroviral therapy (ART) contributes significantly to the disease progression and emergence of drug-resistant HIV. Objective: This study aimed to determine the correlation between the adherence of HIV/AIDS patients to clinical outcomes in Semarang. Method: This was an observational and cross-sectional approach. The instrument used the Simple Medication Adherence Questionnaire (SMAQ), which was validated and distributed to 50 respondents. The data were analyzed using chi-square (p &lt; 0.05), and the results showed a statistically significant relationship. Result: Respondents were male (96%), aged 26-45 years (76%), high school graduates (24%), working (88%), single (86%), without comorbidity (86%), length of treatment more than 12 months (80%), and general treatment (50%). A total of 31 respondents (62%) adhered to treatment with the combination regimen of Tenofovir/Lamivudine/Efavirenz (20%). There was a significant relationship (p = 0.006) between the length of treatment and patient adherence. The adherence results were not significantly related (p &gt; 0.05) to virological outcomes. Conclusion: There is no significant relationship between the adherence of HIV/AIDS patients and clinical outcomes.

Drug resistance and influencing factors in HIV-1-infected individuals under antiretroviral therapy in Guangxi, China.

To assess the profiles and determinants of drug resistance in HIV-1-infected individuals undergoing ART in Guangxi. Samples and data were collected from HIV-1-infected individuals experiencing virological failure post-ART from 14 cities in Guangxi. Sequencing of the HIV-1 pol gene was conducted, followed by analysis for drug resistance mutations using the Stanford University HIV Drug Resistance Database. Logistic regression was employed to identify potential risk factors associated with both HIV drug resistance and mortality. A total of 8963 individuals with pol sequences were included in this study. The overall prevalence of HIV-1 drug resistance (HIVDR) was 42.43% (3808/8963), showing a decrease from 59.62% to 41.40% from 2016 to 2023. Factors such as being aged ≥50 years, male, Han nationality, lower education levels, occupations including workers, peasants and children, AIDS, pre-treatment CD4 T cell counts <200 cells/mm3, infection with CRF01_AE and CRF55_01B subtypes, and ART regimen lamivudine/zidovudine/nevirapine were associated with higher susceptibility to HIVDR. The common mutations were M184V (17.38%) and K103N (22.14%). Additionally, the prevalence of M184V, S68G, M41L and G190A were different between the Han and Zhuang populations. Factors including age, gender, ethnicity, education level, occupation, infectious route, clinical stage, viral load, subtype, ART regimen and HIVDR showed significant associations with mortality. The factors contributing to drug resistance in the HIV-1 ART individuals in Guangxi appear to be notably intricate. Continuous reinforcement of drug resistance surveillance is imperative, accompanied by the optimization of ART regimens to mitigate virological failures effectively.

Trends of pre-treatment drug resistance in antiretroviral-naïve people with HIV-1 in the era of second-generation integrase strand-transfer inhibitors in Taiwan.

Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001). After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.

Prevalence of pretreatment HIV resistance to integrase inhibitors in West African and Southeast Asian countries.

Integrase strand transfer inhibitors (INSTIs) have been recently recommended as the preferred first-line option for antiretroviral treatment initiators in low- and middle-income countries (LMICs) in response to the growing circulation of resistant HIV to non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this study, we estimated the frequency of pretreatment drug resistance (PDR) to INSTIs in West Africa and Southeast Asia. Using samples collected from 2015 to 2016, and previously used to assessed PI, NRTI and NNRTI resistance, we generated HIV integrase sequences and identified relevant INSTI PDR mutations using the Stanford and ANRS algorithms. We generated 353 integrase sequences. INSTI PDR frequency was low, 1.1% (4/353) overall, ranging from 0% to 6.3% according to country. However, frequency of PDR to any drug class was very high, 17.9% (95% CI: 13.9%-22.3%), and mostly associated with a high level of NNRTI PDR, 9.7%, and a moderate level of NRTI PDR, 5.3%. Our results support the recent introduction of INSTIs in LMICs to improve treatment outcome in these settings, but also stress the need for effective actions to prevent uncontrolled emergence of drug resistance to this drug class.

Pre-Exposure Prophylaxis for HIV: Bioethical, Clinical, and Epidemiological Considerations.

Public health authorities are broadly promoting a strategy known as pre-exposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) transmission in the context of high-risk sexual activity and injection drug use. However, there are several limitations to this strategy that are underrecognized. This article reviews the primary literature supporting the use of PrEP and explores the unintended consequences associated with its use. Current public health messaging indicates that PrEP reduces the risk of HIV transmission during sex by 99 percent; however, this figure is based on modeling rather than study findings, and real-world efficacy may be significantly lower. PrEP has been associated with increased rates of sexually transmitted infections, risk compensation, HIV drug resistance, low adherence, and drug side effects. To make fully informed decisions, medical professionals and patients should be aware of these pitfalls. Additionally, this article explores the bioethical implications of prescribing PrEP from a Catholic perspective. Although not always morally illicit, PrEP is most often prescribed in the context of sexual activity outside of marriage between a biological male and female, placing the prescriber in cooperation with activity deemed to be immoral by the Catholic Church. While all medical professionals seeking the common good should aim to reduce the transmission of HIV, not all means are morally licit. Conscience protection for medical professionals opposed to this strategy has become increasingly relevant. Thoughtful discernment is necessary when considering PrEP. Summary: The use of CDC material (figure 1) in this article does not imply endorsement by CDC. The material is in the public domain and available on the CDC website free of charge.

HIV-1 drug resistance-associated mutations in relation to viral load among HIV/AIDS patients at Dr. M. Djamil-Hospital Padang

BackgroundAccording to the WHO, 38 million people suffer from HIV worldwide and according to the HIV Drug Resistance Report, the prevalence of antiretroviral therapy (ART) resistance is 3-29%. Drug resistance-associated mutations (DRAMs) are the presence of one or more HIV mutations that reduce the ability of certain drugs to inhibit viral replication and that will increase viral replication and HIV RNA, which can lead to therapeutic failure. The objective of this study was to determine the prevalence of HIV-1 DRAMs among patients with chronic HIV-1 infections and to compare HIV RNA viral load between M184V and K103N mutations. Methods A cross-sectional was conducted involving 80 patients with HIV who met the inclusion criteria. The study subjects were examined for genotype and HIV RNA viral load, both using the polymerase chain reaction (PCR). Data were analyzed with the Kruskal-Wallis test. Results The overall drug resistance mutation prevalence was 10.0%. The most common mutations were M184V and K103N. There was a significant difference between the median HIV RNA viral load counts in patients with either M184V or K103N, and with both M184V and K103N mutations, the values being 45.420, 13.207, and 97.517 copies/mL, respectively (p&lt;0.001). Conclusion The HIV RNA viral load count was higher in the mutation group than in the group without mutation. Long-term and ongoing surveillance of HIV DRAMs among these patients is necessary, which will help us to adjust the treatment regimen.

HIV-1 Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-Exposure Prophylaxis: Pooled Analysis From 72 Global Studies.

Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings. HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentration in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies. Among 17,274 participants, there were 101 cases with new HIV-1 diagnosis (0.77 per 100 person-years; 95% CI 0.63-0.94). In 78 cases with resistance data, 18 (23%) had M184I or V, one (1.3%) had K65R, and three (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/week, respectively, and the corresponding incidence was 3.9 (95% CI 2.9-5.3), 0.24 (0.060-0.95), 0.27 (0.12-0.60), and 0.054 (0.008-0.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports. Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.

HIV protease resistance mutations in patients receiving second-line antiretroviral therapy in Libreville, Gabon

IntroductionIn 2022, the WHO reported that 29.8 million people around the world were living with HIV (PLHIV) and receiving antiretroviral treatment (ART), including 25‌ 375 people in Gabon (54% of all those living with HIV in the country). The literature reports a frequency of therapeutic failure with first-line antiretrovirals (ARVs) of between 20% and 82%. Unfortunately, data relating to the failure of second-line ARVs are scarce in Gabon. This study aims to determine the profiles of HIV drug resistance mutations related to protease inhibitors in Gabon.MethodologyPlasma from 84 PLHIV receiving ARVs was collected from 2019 to 2021, followed by RNA extraction, amplification, and sequencing of the protease gene. ARV resistance profiles were generated using the Stanford interpretation algorithm version 8.9-1 (https://hivdb.stanford.edu) and statistical analyses were performed using EpiInfo software version 7.2.1.0 (CDC, USA).ResultsOf 84 HIV plasma samples collected from 45 men and 39 women, 342 mutations were detected. Of these, 43.3% (148/342) were associated with nucleoside reverse transcriptase inhibitors (NRTIs), 30.4% (104/342) with non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 26.3% (90/342) with protease inhibitors (PIs). Most NRTI mutations were associated with thymidine analogues (TAMs) (50.7%; 75/148), including T215F/V (14.9%; 22/148), D67DN/E/G/N/T (10.1%; 15/148), M41L (9.5%; 14/148), and K70E/KN/S/R (9.5%; 14/148). Resistance mutations related to non-TAM NRTIs (33.1%; 49/148) were M184V (29.1%; 43/148), and L74I/V (8.1%; 12/148). NNRTI mutations were predominantly K103N/S (32.7%; 34/104), V108I (10.6%; 11/104), A98G (10.6%; 11/104), and P225H (9.6%; 10/104). Minor mutations associated with PIs (60.0%; 54/90) were predominantly K20I (15.6%; 14/90) and L10F/I/V (14.5%; 13/90). The major mutations associated with PIs (40.0%; 36/90) were M41L (12.2%; 11/90), I84V (6.7%; 06/90), and V82A (6.7%; 06/90). The four most prescribed therapeutic regimens were TDF + 3TC + LPV/r (20.3%; 17/84), ABC + DDI + LPV/r (17.9%; 15/84), TDF + FTC + LPV/r (11.9%; 10/84), and ABC + 3TC + LPV/r (11.9%; 10/84).ConclusionThis study revealed that HIV drug resistance mutations are common in Gabon. The major mutations associated with PIs were M41L, I84V, and V82A. There is a need for access to new NRTIs, NNRTIs, and PIs for a better therapeutic management of PLHIV in Gabon.

Viremia and HIV Drug Resistance Among People Receiving Dolutegravir Versus Efavirenz-Based First-Line Antiretroviral Therapy.

Viremia and HIV Drug Resistance Among People Receiving Dolutegravir Versus Efavirenz-Based First-Line Antiretroviral Therapy.

Drug resistance in HIV's interaction with reverse transcriptase and integrase strand transfer inhibitors among Nigerians attending a military Hhospital

Drug resistance in HIV's interaction with reverse transcriptase and integrase strand transfer inhibitors among Nigerians attending a military Hhospital

Checking the Status: The Evolutionary Explanations and Drug Resistance Prevalence to Dolutegravir for HIV Treatment (A Review)

Drug treatment advancements for HIV have dramatically advanced since the virus’ identification in the early 1980s. Integrase strand transfer inhibitors (INSTIs) are one of seven HIV treatment drug classes currently utilized to create an undetectable viral count in blood samples of people living with HIV (PLWH). First generation INSTIs are documented with low barriers of genetic resistance, which indicates that the number of mutations to lead to a drug resistant mutation is low. The introduction of dolutegravir, a second generation INSTI, shows a higher barrier of genetic resistance that will reduce drug resistant mutations to INSTIs and increase the overall effectiveness of this class of HIV treatment. PLWH can be categorized based on whether they received treatment previously/currently or have never received treatment. Therapy naive and previously treated (successfully or unsuccessfully) patients for HIV report different rates of drug resistant mutations compared to actual resistance to dolutegravir, 0.4-31% and 0.1-67.2% respectively. Evolutionary considerations of genetic resistance, including epistatic interactions and point mutations, suggest both non-polymorphic and polymorphic mutations for these drug resistant mutations. An incomplete understanding of how evolutionary factors contribute to HIV drug resistance highlights the importance of conducting further research. This research may help improve the efficacy of second generation INSTIs in future treatment options for PLWH. This review describes the landscape of existing research on drug resistance prevalence for dolutegravir and possible evolutionary explanations on how these mutations arise in the first place, leading to implications in developing more robust treatment modalities.

Developing a reporting item checklist for studies of HIV drug resistance prevalence or incidence: a mixed methods study

BackgroundAdequate surveillance of HIV drug resistance prevalence is challenged by heterogenous and inadequate data reporting. To address this issue, we recently published reporting guidance documentation for studies of HIV drug...