Antiretroviral Failure Research Articles

People living with HIV co-infected with the Kaposi Sarcoma-associated Herpes Virus have a distinct HIV Tat profile and higher rates of antiretroviral virologic failure, more evident among those with Kaposi's sarcoma.

Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma-associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV-1 TAT protein can be essential in developing AIDS-associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV-specific TAT profile among PLHIV who developed KS.

Determinants of virological failure among HIV clients on second-line antiretroviral treatment at Felege-hiwot and University of Gondar comprehensive specialized hospitals in the Amhara Region, Northwest Ethiopia: A case-control study.

Second-line HIV treatment failure has become increasing worldwide, mainly in sub-Sahara Africa including Ethiopia. Even though the problem becomes increasing, inadequate information was available about its magnitude and associated factors in the current study area. To assess the factors of second-line Anti-Retroviral Treatment virological failure among second-line ART users. Institutional-based unmatched case-control study design was conducted from September to December 2021 at Felege Hiowt and University of Gondar Comprehensive Specialized Hospitals; Amhara region, Northwest Ethiopia. A total of 216 patients (60 cases and 156 controls) were recruited by a simple random sampling technique with a 1:3 cases-to-controls ratio. Patients who had two viral load results >1000 copies/ml within a 3-month interval after taking ART drugs for at least 6 months were cases and those who had ≤1,000 copies/ mL were controls. The sample size was calculated by using Epi-Info version 7.2.4. Structured questionnaires were used to gather the required information. SPSS version 26 was used to summarize the findings. In bivariate logistic regression model, Variables with two-tailed P-value ≤ 0.25 at 95% confidence interval were transferred into multivariate binary logistic regression model and P value at ≤ 0.05 was set as statistically significant. Out of 216 patients recruited, 212 have participated with a response rate of 98.2%. From these participants, 117(55.2%) were males and 187(88.2%) were urban dwellers. Among the total respondents, 208(98.1%) had age > 24 years, 200(94.3) were at HIV clinical stage I, 72(34%) had poor ART adherence and 112(52.8) did not disclose their HIV status. Likewise, most of the patients 147(69.37) didn't use condoms. The associated factors were not disclosing HIV status (AOR = 3.4, 95% CI: 1.52-7.79), medium adherence (AOR = 3.7, 95% CI = 1.3-10.7), poor adherence level (AOR = 5.27, 95% CI: 2.2-12.5), not using condoms (AOR = 4.47, 95% CI: 1.63-12.2) and Viral load (>150 copies/ml) when switched to second-line ART (AOR = 3.56, 95% CI: 1.5-8). Non-disclosure, poor or medium adherence, not using condoms and high Viral load (>150 copes/ml) when switched to second-line ART were the main factors for second-line Anti-Retroviral Treatment virological failure. Disclosure about HIV status, using condoms and improving treatment adherence level are crucial to reduce second-line virological failure.

Paediatric antiretroviral therapy challenges with emerging integrase resistance.

Universal antiretroviral (ART) coverage and virological suppression are fundamental to ending AIDS in children by 2030. Availability of new paediatric dolutegravir (DTG)-based ART formulations is a major breakthrough and will undoubtedly help achieve this goal, but treatment challenges still remain. Paediatric formulations remain limited compared to those for adults, especially for young children, those unable to tolerate DTG or with DTG-based first-line ART failure. Tenofovir alafenamide is virologically superior to standard-of-care backbone drugs in second-line, but paediatric formulations are not widely available. The roles of resistance testing and recycling of backbone drugs following first-line ART failure remain to be determined. Results of trials of novel treatment strategies including dual therapy and long-acting agents are awaited. Although numbers are currently small, safe and effective ART options are urgently required for children developing DTG resistance. The antiretroviral treatment gap between adults and children persists. The potential benefits from rollout of new paediatric DTG-based fixed-dose combination ART for first-line treatment are considerable. However, children remain disadvantaged when DTG-based first-line ART fails or cannot be used. Research efforts to address this inequity require prioritisation in order to ensure health outcomes are optimised for all ages in all settings.

Highly active antiretroviral therapy discontinuation time is associated with therapeutic failure among human immunodeficiency virus (HIV)-infected immigrant adults: A cohort study from a Peruvian referral hospital during the Venezuelan exodus.

To evaluate the association between Highly Active Antiretroviral Therapy (HAART) discontinuation time and therapeutic failure (TF) in Venezuelan immigrants with HIV that restart HAART. We carried out a retrospective cohort study in a large hospital in Peru. We included Venezuelan immigrants who restarted HAART and were followed over at least 6 months. The primary outcome was TF. Secondary outcomes were immunologic (IF), virologic (VF) and clinical (CF) failures. The exposure variable was HAART discontinuation, categorised as no discontinuation, less than 6 months, and 6 months or more. We applied generalised linear models Poisson family with robust standard errors to calculate crude (cRR) and adjusted (aRR) relative risks by statistical and epidemiological criteria. We included 294 patients, 97.2% were males, and the median age was 32 years. Out of all the patients, 32.7% discontinued HAART for less than 6 months, 15.0% discontinued for more than 6 months and the remaining 52.3% did not discontinue. The cumulative incidence of TF was 27.9%, 24.5% in VF, 6.0% in IF and 6.0% in CF. Compared with non-discontinued HAART patients, the discontinuation for less than 6 months (aRR = 1.98 [95% CI: 1.27-3.09]) and from 6 months to more (aRR = 3.17 [95% CI: 2.02-4.95]) increased the risk of TF. Likewise, treatment discontinuation of up to 6 months (aRR = 2.32 [95% CI: 1.40-3.84]) and from 6 months to more (aRR = 3.93 [95% CI: 2.39-6.45]) increased the risk of VF. HAART discontinuation increases the probability of TF and VF in Venezuelan immigrants.

1270. HIV Drug Resistance and Viral Outcomes after 2nd-line Antiretroviral Failure in Kenya

Abstract Background Program data on HIV drug resistance and clinical outcomes after 2nd-line antiretroviral therapy (ART) failure in resource-limited settings are limited, yet can inform care, particularly with better ART access and options. Methods We examined resistance upon 2nd-line failure and subsequent viral outcomes at the Academic Model Providing Access to Healthcare (AMPATH) in Kenya. Charts of people with genotypes upon 2nd-line failure up to 6/2021 were reviewed; and associations with viral suppression (< 1000 copies/mL) closest to 12 months post-genotyping were determined using bi- and multivariate analyses, adjusting for age, sex, time on ART, switch to 3rd-line (darunavir-, dolutegravir-, and/or raltegravir-based ART), and any resistance to regimens upon viral load (VL) testing. Results Of 194 participants (53% female; median age 41 years; median 3.3 and 4.1 years on 1st- and 2nd-line), 60% were on lopinavir/ritonavir and 40% on atazanavir/ritonavir-based regimens. Overall, 178 (92%) had any resistance: 19% mono-, 40% dual-, 41% triple-class; 79% to NRTIs; 81% NNRTIs; and 43% PIs - 33% of those on lopinavir/ritonavir; 58% on atazanavir/ritonavir (p< 0.001); 24% with intermediate-high predicted resistance to darunavir/ritonavir (12 upon LPV/ritonavir, and 8 upon atazanavir/ritonavir failure; p=0.98). Of 140/194 people with post-genotype VLs, 55% stayed on 2nd-line, and 45% switched to 3rd-line. Of those 140, 72% virally suppressed (89% who switched to 3rd-line; 58% who didn't), and 75% had any resistance to their regimen at post-genotype VL (90% who switched to 3rd-line; 62% who didn't). In bivariate analysis, suppression was associated with switching to 3rd-line, and with resistance upon VL testing (Table). In multivariate analysis, suppression remained more likely among those who switched to 3rd-line, and association with resistance was less pronounced. Conclusion In a large Kenyan HIV program, high resistance upon 2nd-line failure, high failure rates, and suppression association with 3rd-line switch suggest the need for dedicated management of this vulnerable population. Potential association between resistance and better viral outcomes, similar to reports upon 1st-line failure, needs further data and suggests significance of inadequate adherence. Disclosures All Authors: No reported disclosures.

The Associations between Mental Health Literacy and HIV-related Treatment Outcomes among HIV/AIDS Outpatients in Vietnam

Data about mental health literacy and its associations with HIV-related treatment outcomes are both sparsely reported and presented with disparate results. This study aimed to assess the mental health performance among HIV/AIDS outpatients and examine the correlations between Mental Health Literacy Scale (MHLS) with some pre-specified HIV-related treatment outcomes, including clinical status, HIV-RNA suppression, antiretroviral (ART) failure, and treatment adherence. We conducted a single-center, cross-sectional study between June and October 2020 in Ho Chi Minh City, Vietnam. Adult HIV-infected patients were enrolled in the study when they routinely attended an outpatient clinic to receive medical consultations and antiretroviral therapy. Bivariate logistic regressions were used to study the associations between MHLS and major HIV-related health outcomes. A total of 406 HIV-infected participants were enrolled during the study period. The median MHLS among HIV/AIDS patients was 99 (Interquartile range (IQR): 93-107). Roughly 93% of patients were clinically stable, with a median CD4 count of 603 cells/µl. Two-thirds of patients achieved HIV-RNA suppression (undetectable threshold < 20 copies/ml). A total of thirteen (3.2%) patients were undertaking protease-inhibitors-based second-line ART regimens. The ART compliance of participants was evaluated at 92.1%. The logistic bivariate analyses did not show any significant correlations between mental health literacy with both pre-specified HIV-related health outcomes and ART adherence. The mental health performance among the HIV/AIDS outpatients at the HIV community-based clinic was at the intermediate level. The mental health literacy of patients was not statistically associated with the pre-specified HIV treatment outcomes.

Antiretroviral Drug-Resistance Mutations on the Gag Gene: Mutation Dynamics during Analytic Treatment Interruption among Individuals Experiencing Virologic Failure.

We describe drug-resistance mutation dynamics of the gag gene among individuals under antiretroviral virologic failure who underwent analytical treatment interruption (ATI). These mutations occur in and around the cleavage sites that form the particles that become the mature HIV-1 virus. The study involved a 12-week interruption in antiretroviral therapy (ART) and sequencing of the gag gene in 38 individuals experiencing virologic failure and harboring triple-class resistant HIV strains. Regions of the gag gene surrounding the NC-p2 and p1-p6 cleavage sites were sequenced at baseline before ATI and after 12 weeks from plasma HIV RNA using population-based Sanger sequencing. Fourteen of the sixteen patients sequenced presented at least one mutation in the gag gene at baseline, with an average of 4.93 mutations per patient. All the mutations had reverted to the wild type by the end of the study. Mutations in the gag gene complement mutations in the pol gene to restore HIV fitness. Those mutations around cleavage sites and within substrates contribute to protease inhibitor resistance and difficulty in re-establishing effective virologic suppression. ART interruption in the presence of antiretroviral resistant HIV strains was used here as a practical measure for more adapted HIV profiles in the absence of ART selective pressure.

Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response

DNA methylation is one of the epigenetic modifications that configures gene transcription programs. This study describes the DNA methylation profile of HIV-infected individuals with distinct characteristics related to natural and artificial viremia control. Sheared DNA from circulating mononuclear cells was subjected to target enrichment bisulfite sequencing designed to cover CpG-rich genomic regions. Gene expression was assessed through RNA-seq. Hypermethylation in virologic responders was highly distributed closer to Transcription Start Sites (p-value = 0.03). Hyper and hypomethylation levels within TSS adjacencies varied according to disease progression status (Kruskal–Wallis, p < 0.001), and specific differentially methylated regions associated genes were identified for each group. The lower the promoter methylation, the higher the gene expression in subjects undergoing virologic failure (R = − 0.82, p = 0.00068). Among the inversely correlated genes, those supporting glycolysis and its related pathways were hypomethylated and up-regulated in virologic failures. Disease progression heterogeneity was associated with distinct DNA methylation patterns in terms of rates and distribution. Methylation was associated with the expression of genes sustaining intracellular glucose metabolism in subjects undergoing antiretroviral virologic failure. Our findings highlight that DNA methylation is associated with latency, disease progression, and fundamental cellular processes.

Fitness Cost of Antiretroviral Drug Resistance Mutations on the pol Gene during Analytical Antiretroviral Treatment Interruption among Individuals Experiencing Virological Failure.

HIV cure studies require patients to enter an analytical treatment interruption (ATI). Here, we describe previously unanalyzed data that sheds light on ATI dynamics in PLHIV (People Living with HIV). We present drug resistance mutation dynamics on the pol gene among individuals with antiretroviral virological failure who underwent ATI. The study involved a 12-week interruption in antiretroviral therapy (ART), monitoring of viral load, CD4+/CD8+ T cell counts, and sequencing of the pol gene from 38 individuals experiencing virological failure and harboring 3-class resistant HIV strains: nucleoside reverse transcriptase inhibitors (NRTI) non-nucleoside inhibitors (NNRTI), and protease inhibitors (PI). Protease and reverse transcriptase regions of the pol gene were sequenced at baseline before ATI and every four weeks thereafter from PBMCs and at baseline and after 12 weeks from plasma HIV RNA using population-based Sanger sequencing. Average viral load increased 0.559 log10 copies per milliliter. CD4+ T cell count decreased as soon as ART was withdrawn, an average loss of 99.0 cells/mL. Forty-three percent of the mutations associated with antiretroviral resistance in PBMCs disappeared and fifty-seven percent of the mutations in plasma reverted to wild type, which was less than the 100% reversion expected. In PBMC, the PI mutations reverted more slowly than reverse transcriptase mutations. The patients were projected to need an average of 33.7 weeks for PI to revert compared with 20.9 weeks for NRTI and 19.8 weeks for NNRTI. Mutations in the pol gene can cause virological failure and difficulty in re-establishing effective virological suppression.

Prevalence of, and Factors Influencing First Line Antiretroviral Treatment Failure among Adult HIV Patients at Antiretroviral Treatment Clinic of Mettu Karl Referral Hospital, South Western, Ethiopia: A Prospective Cross Sectional Study, 2021

Antiretroviral treatment failure is defined as progression of disease and high risk of mortality after beginning of highly active anti-retroviral therapy. First-line ART failure has emerged as a growing concern. ART failure is a major challenge to HIV/AIDS management in resource-limited settings including Ethiopia where the diagnosis and management of ART failure is a key problem. Principal factors involving fist-line antiretroviral regimen failure include poor adherence to medication, younger age, lower baseline CD4+ count and higher baseline viral load.

First-Line Antiretroviral Regimen Failure and Determinants in an Urban HIV Clinic at Phramongkutklao Hospital, Bangkok, Thailand: 20 Years Experience.

PurposeHIV treatment involves antiretroviral therapy (ART) endeavoring to suppress viral load to an undetectable level. Virologic failure occurs when ART fails to suppress and sustain an individual’s viral load to less than 200 copies/mL after 6 months of therapy. In Thailand, the data among first-line antiretroviral regimen failure and determinants remains limited, especially in urban HIV clinics. We aimed to demonstrate factors of first-line antiretroviral regimen failures in an urban HIV/AIDS clinic at Phramongkutklao Hospital.Patients and MethodsA nested case control 1:4 study was conducted. Data were collected from the electronic patient database among naïve people living with HIV/AIDS (PLWHA), aged ≥18 years and receiving ART continuously for at least 2 years at Phramongkutklao Hospital from 1 January 2000 to 31 December 2019. Multiple logistic regression was used to identify the determinants of virologic failure. Adjusted HRs (AHRs) with 95% CIs were used to declare statistical significance.ResultsOf 200 PLWHA included in the study, 40 participants experienced HIV virologic failure. The median time after starting ART to virologic failure was 24 months (IQR 7–96.0). Univariate and multivariate analysis showed significant factors affecting first-line antiretroviral regimen failure included being female (37.5 vs 26.88%, adjusted odds ratio 5.08 [1.05–24.6, p-value 0.043], age ≤40 yr. (62.5 vs 49.6%, adjusted odds ratio 4.59 [1.47–14.37], p-value 0.009), CD4+count ≤200 cell/µL (77.5 vs 52.5%, adjusted odds ratio 4.83 [1.28–18.9], p value 0.02), tuberculosis (42.5 vs 7.5%, adjusted odds ratio 8.66 [2.37–31.56], p value <0.001) and initiation of ART at CD4+ count <350 cell/µL (72.5 vs 48.13%, adjusted odds ratio 31.36 [6.51–151.22], p value <0.001). Estimated prevalence of virologic failure in Phramongkutklao Hospital was 5.34%.ConclusionOur study revealed factors favoring virologic failure included being female, younger age, CD4+ count <200 cells/µL, tuberculosis and initiation of ART at CD4+ count <350 cell/µL. Multidisciplinary HIV comprehensive care teams should encourage patient adherence and support patients along HIV continuum of care to prevent virologic failure and drug resistance, especially among patients initiating ART at low CD4+ count and tuberculosis co-infection.

Poor quality of life and incomplete self-reported adherence predict second-line ART virological failure in resource-limited settings

ABSTRACT We evaluated health-related quality of life (QoL) and self-reported incomplete adherence as predictors of early second-line antiretroviral (ART) virological failure (VF). ACTG A5273 study participants completed the ACTG SF-21 measure which has 8 QoL domains. We used exact logistic regression to assess the association of QoL at baseline and week 4 with early VF adjusted for self-reported adherence. Of 500 individuals (51% women, median age 39 years) in this analysis, 79% and 75% self-reported complete adherence (no missing doses in the past month) at weeks 4 and 24, respectively. Early VF was experienced by 7% and more common among those who self-reported incomplete adherence. Participants with low week 4 QoL scores had higher rates of early VF than participants with high scores. After adjusting for self-reported adherence at week 4, VL and CD4 at baseline, cognitive functioning, pain and mental health domains were significantly associated with subsequent early VF. In this post-hoc analysis, poorer QoL adds to self-reported incomplete adherence after 4 weeks of second-line ART in predicting VF at week 24. Evaluation is needed to assess whether individuals with poorer QoL might be targeted for greater support to reduce risk of VF. Trial registration: ClinicalTrials.gov identifier: NCT01352715.

HIV-1 transmitted drug resistance in Brighton, UK, from 2014 to 2020.

HIV-1 transmitted drug resistance (TDR) is associated with transmission in men who have sex with men (MSM), non MSM clusters, sexually transmitted infections (STIs) and can lead to antiretroviral failure. UK guidelines recommend performing TDR testing in all newly-diagnosed people living with HIV. We audited performance of TDR in our large tertiary HIV department from 2014-2020. All new patients had TDR testing attempted in the study period. The rate of TDR was 8% and was associated with increasing age and having non-B subtype. Having non-B subtype was not associated with being non-UK born. Thirty-four percent of people were diagnosed with a bacterial STI at the time of HIV diagnosis, but STI diagnosis was not associated with TDR. There was no significant change in TDR over the 6-year audit period. TDR remains a small but significant problem. Identifying these populations and providing effective HIV prevention interventions will reduce HIV incidence and TDR.

Impact of revised antiretroviral treatment on the immunological, virological and clinical parameters among people infected with HIV

Introduction: In resource-limited countries like India, where resistance testing is often not available, an accurate treatment history can guide doctors in quantifying suboptimal drug exposure and thus anticipate drug resistance Materials and Methods: In the present longitudinal study, a total of 75 patients failing antiretroviral therapy; the effective drug exposure was calculated after taking into account the adherence, appropriateness of prescriptions, and pharmacokinetic interactions. Treatment was modified and patients were followed up. Results: Of the total 75 patients included in the study; 69 (92.0%), 63 (84.0%) and 42 (56.0%) patients had virological, immunological and clinical failure respectively. Suspected reasons for antiretroviral drug failure were non-adherence in 48 (64.0%), improper prescriptions in 12(16.0%) and drug interactions in 12 (16.0%). We observed that following treatment change, CD4 count increased by a mean of 127 cells/?l and 33 (44.0%) patients had fully suppressed viral loads. Conclusion: Our results show that empirical treatment changes based on a comprehensive drug history, followed by good adherence lead to good treatment outcomes in patients showing one or other evidence of drug resistance. Keywords: HIV, AIDS, Drug-resistance, Antiretroviral.

Second line anti-retroviral therapy failure in a pediatric cohort of an Ethiopian tertiary hospital: A retrospective observational study

Background: Sub-Saharan Africa carries the largest burden of pediatric HIV infection. The extent and factors affecting the success of second line anti-retroviral treatment in the region have not been well-studied. This study aimed to determine the rate and determinants of failure of second line anti-retroviral treatment among children and adolescents on follow-up at an Ethiopian tertiary teaching hospital. Methods and materials: A retrospective observational cohort study was conducted at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. Structured data abstraction forms were used to collect socio-demographic, clinical and diagnostic data. Descriptive statistics and bivariate analysis were used to describe the magnitude of the problem and its associations. Results: A total of 76 children and adolescents who were taking second line anti-retroviral treatment and had at least a single viral load determination while under care were analyzed. Their mean age was 16.1 years. Failure of second line anti-retroviral drugs was seen in 14 of the 76 while 4 of them fulfilled eligibility criteria for a switch to third line anti-retroviral treatment. The mean duration till virologic failure was 17.6 months. The mean CD4 and viral load upon requirement of a third line regimen was 612.2/mm3 and 82,131.3 copies/ml. Second line antiretroviral treatment virologic failure was significantly associated with the age of the child or adolescent. Conclusion: There was a high rate of virologic failure among children and adolescents under second line anti-retroviral drugs in our hospital. Our findings also highlight the need for provision of third line second line anti-retroviral drugs. Challenges for delivering a standard care were infrequent viral load testing and delayed initiation of second line treatment after confirming failure of first line regimens.

Marked decrease in acquired resistance to antiretrovirals in latest years in Italy

ObjectivesThe aim of this study was to evaluate acquired drug resistance in Italy in the 2009–2018 period. MethodsWe analysed 3094 patients from the Italian ARCA database who had failed antiretroviral treatment and who had received a genotypic test after 6 months of treatment. Drug resistance mutations were identified using International AIDS Society (IAS)-USA tables and the Stanford HIVdb algorithm. The global burden of acquired resistance was calculated among all subjects with antiretroviral failure. Time trends and correlates of resistance were analysed using standard statistical tests. ResultsPatients of non-European origin and non-B subtypes increased significantly from 11.5% (103/896) to 19.2% (33/172) and from 13.1% (141/1079) to 23.8% (53/223), respectively, over time. Overall, 14.5% (448/3094), 12.1% (374/3094) and 37.8% (1169/3094) of patients failed first, second and later lines, respectively. According to both IAS and HIVdb, in the study period resistance to any class, nucleoside reverse inhibitor, non-nucleoside reverse inhibitor, and protease inhibitors (PIs) declined significantly. Integrase strand transfer inhibitor (INSTI) resistance declined significantly from 31% (36/116) to 20.8% (41/197) according to HIVdb but not to IAS. Divergent data were highlighted regarding the proportion of non-European patients carrying any, PI and INSTI resistance using IAS tables compared with the Stanford HIVdb algorithm, as the former failed to detect a decrease in resistance while the latter indicates a reduction of 1.6-, 5- and 1.8-fold resistance for such drug classes. In the multivariate analysis, the risk of resistance increased in patients with a larger number of treatment lines and higher viraemia and decreased in those starting therapy in the last biennium of the study. DiscussionA marked reduction in drug resistance was observed over 10 years, compatible with higher genetic barrier and potency of new antiretrovirals. Nonetheless, concerns remain for subjects with non-B subtypes when using mutation lists instead of interpretation systems because of the extensive polymorphism of the protease region.

Second line anti-retroviral therapy failure in a pediatric cohort of an Ethiopian tertiary hospital: a retrospective observational study

Sub-Saharan Africa carries the largest burden of pediatric HIV infection. The success of second line anti-retroviral treatment and related factors among African children is not well-defined. Objectives: We aimed to identify the rate and determinants of second line anti-retroviral treatment failure among children and adolescents on follow-up at an Ethiopian tertiary teaching hospital. A retrospective observational cohort study was conducted at Tikur Anbessa Specialized Hospital, Addis Ababa. Structured forms were used to collect socio-demographic, clinical and diagnostic data. Descriptive statistics and bivariate analysis were used to describe the magnitude of the problem and its associations. A total of 76 children and adolescents taking second line anti-retroviral treatment were analyzed (mean age: 16.1 years). Failure of therapy was seen in 14/76 while four were eligible for a switch to third line anti-retrovirals. Mean duration on second line treatment till virologic failure was diagnosed was 17.6 months while mean viral load upon requiring a third line regimen was 82,131.3 copies/ml. Second line antiretroviral treatment virologic failure was significantly associated with the age of the child or adolescent. A high rate of virologic failure exists among the study population. Findings underline need for provision of third line anti-retroviral drugs in Ethiopia. Challenges for delivering a standard care were irregular viral load testing and delayed initiation of second line treatment after failure of first line regimens.

HIV MOLECULAR EPIDEMIOLOGY AND PHARMACO-RESISTANCE IN PATIENTS WITH ANTIRETROVIRAL THERAPY FAILURE IN ARKHANGELSK DISTRICT

Introduction . The HIV epidemic remains the most devastating in the history of mankind, despite comprehensive preventive measures. The HIV pharmacological resistance to several groups drugs at once is particular importance since this significantly reduces the therapy possibilities. Due to the low adherence to the treatment of patients certain categories, as well as the HIV drug-resistant transmission under various conditions possibility, treatment may not give positive results in 16–27% of patients who did not receive ART and in 50–70% of previously treated patients. The aim of our work was to evaluate the molecular-epidemiological structure and pharmacoresistant HIV variants in patients with antiretroviral therapy virologic failure in Arkhangelsk. Materials and methods. To evaluate the molecular-epidemiological structure and pharmacoresistant HIV variants in 76 HIV-infected patients with virologic failure of antiretroviral therapy from the Arkhangelsk region, HIV polymerase gene ( pol ) nucleotide sequences were analyzed. Results. In the examined group, HIV subtype A6 (IDU-A) prevailed (89,5%) compared with subtype B (9,2%), in one case (1,3%) the variant CRF03_AB was detected. For 86,8% of patients, resistance to any drugs was determined. Including resistance to protease inhibitors mutations — 33,3%, to revertase inhibitors — 92,4%. Isolates with pharmacoresistance only to NRTIs amounted to 16,6%, to NNRTIs 1,5%, to PI 10,6%, simultaneously to PI and NRTIs 12,1%, to NRTIs and NNRTIs 46,96%, to all three groups of drugs at the same time — 12,1%. The most common mutations are drug resistance to lamivudine and emtricitabine (M184V), nevirapine and efavirenze (K103N, G190S), thymidine analogs (T215F/Y and/or K219Q/E and/or D67N), and non-thymidine L nucleoside analogues).

Factors Associated with Antiretroviral Treatments Failure among HIV-Positive Patients in Congo: A Retrospective Cohort Study

Background: Viral load is the key indicator of the effectiveness of antiretroviral treatment in HIV patients. Study aimed to determine antiretroviral treatments failure rates and associated risk factors among HIV-infected adult patients in Congo. Methods: Data from the Congolese AIDS and Epidemics Control Council were combined to create a historical cohort. Patients were followed up between 2003 to 2017. Mixed logistic regression was used to identify treatment failure associated-factors. Intercooled Stata 10 (StataCorp LP, College Station, Texas, USA) software packages was used for analysis. Results: Over 14 years of follow-up, a total of 25,500 visits for 6391 adult patients were reported. Among them, 88% i.e. 22,328 visits (for a total of 6127 patients) were visits with treatment failure. In the multivariate analysis, being aged >26 years, having primary education level, being student, others nationality, unspecifiedmarital status and being worker in informal sector were found associated with a higher risk of treatment failure. Conversely, being pensioners, receiving second line therapeutic protocols and having good adherence to treatment were found significantly associated with a lower risk of treatment failure. Conclusion: Antiretroviral treatments failure among HIV-treated patients is common in Congo. Developing treatment adherence-centered interventions with focus in patients who have low socio-economic status needed to reduced treatments failure. As treatment failure is not only determined by individual factors, psychosocial supports and availability of antiretroviral drugs needs to be taken into account.

Evidence of genomic information and structural restrictions of HIV-1 PR and RT gene regions from individuals experiencing antiretroviral virologic failure

ObjectivesThis study analyzed Protease-PR and Reverse Transcriptase-RT HIV-1 genomic information entropy metrics among patients under antiretroviral virologic failure, according to the numbers of virologic failures or resistance mutations. MethodsFor this purpose, we used genomic sequences from PR and RT of HIV-1 from a cohort of chronic patients followed up at São Paulo Hospital. ResultsInformational entropy proportionally increases with the number of antiretroviral virologic failures in PR and RT (p < .001). Affected regions of PR were related to catalytic and structural functions, such as Fulcrum (K20) Flap (M46) and Cantilever (A71). In RT, this occurred at Fingers (E44) and Palm (K219). Informational entropy increases according to the number of resistance mutations in PR and RT (p < .001). Higher PR entropy was proportional to the resistance mutation numbers in Fulcrum (L10), Active site (L24) Flap (M46), Cantilever (L63) and near Interface (L90). In RT, they related to regions responsible for protein stability such as Fingers (T39) and Palm (L100). ConclusionsThe antiretroviral selective pressure affects HIV genomic informational entropy at the PR and RT regions, leading to the emergence of more unstable virions. Mapping the three-dimensional structure in these HIV-1 proteins is relevant to designing new antiretroviral targeting resistant strains.