Virological Treatment Failure Research Articles

Analysis of genotype resistance and HIV-1 transmission risk in HIV-1-infected men who have sex with men in Guiyang, China.

As the social economy has developed and population mobility has increased, differences in the Human immunodeficiency virus type 1 (HIV-1) genotype distribution among men who have sex with men (MSM) have become apparent in the provinces and cities across China. The high variability and drug resistance characteristics of HIV-1 can lead to the widespread spread of resistant strains, which may also result in antiretroviral therapy failure and an increase in the mortality rate. The genotypic drug resistance characteristics and HIV-1 transmission risks among HIV-1-infected MSM in Guiyang, Guizhou Province were analyzed in the current study. The aim of the study was to provide a scientific basis for preventing the spread of HIV-1 strains among MSM and develop intervention measures. A cross-sectional study was conducted at the Guiyang Public Health Clinical Center. A total of 181 HIV-1-infected MSM who not received treatment at the center between 1 January 2020 and 31 December 2022 were selected. The HIV-1 pol region gene fragment, including the protease and reverse transcriptase regions, was amplified by nested PCR and RT-PCR. The maximum likelihood method was used to construct a phylogenetic tree for analyzing the HIV-1 genotypes in MSM. HIV-1 genotypic resistance was evaluated using the Stanford University HIV drug resistance database. A molecular transmission network of HIV was constructed and the risk of HIV-1 transmission was determined. We successfully amplified 173 pol gene sequences from blood samples obtained from 181 patients. The main subtype was CRF07_BC (60.69% [105/173]), followed by CRF01_AE (26.59% [46/173]), CRF08_BC (4.05% [7/173]), CRF55_01B (4.62% [8/173]), B (3.47% [6/173]), and C (0.58% [1/173]). The distribution of HIV-1 genotypes in MSM showed that there was a significant difference in the genotype composition of HIV-1-infected MSM according to registered residences and ages (p < .05). The CRF55_01B subtype accounted for the lowest proportion in Guiyang City and individuals >30 years of age. Multivariate logistic regression analysis of risk factors for drug resistance in HIV-1-infected MSM showed that the overall prevalence of pretreatment drug-resistant species was 12.72% (22/173), and age >30 years, CRF55_01B subtype, and CD4+ T lymphocyte count >350 cells/mm3 were risk factors for drug resistance in MSM HIV-1 strains. Among the pretreatment drug-resistant species, non-nucleoside reverse transcriptase inhibitors with ≥1 drug resistant-species accounted for 9.25% (16/173), followed by protease inhibitors at 4.05% (7/173) and nucleoside reverse transcriptase inhibitors at 1.73% (3/173). Non-nucleoside reverse transcriptase inhibitors resistant to the CRF07_BC and CRF01_AE genotypes were predominant. The CRF55_01B genotype was shown to be most likely to carry the V179E mutation. The molecular network included CRF07_BC and B genotypes. The results of multi-factor logistic regression analysis on the factors affecting the rate of joining the network showed that individuals >30 years of age were less likely to join the network compared to those individuals <30 years of age. The distribution of HIV-1 genotypes among MSM in Guiyang is diverse and complex. The main genotypes were shown to be CRF07_BC and CRF01_AE. The drug resistance mutation rate is high and pretreatment drug-resistant species is at a moderate level of prevalence, with NNRTIs being the most common site for drug resistance mutations. The CRF07_BC subtype and patients <30 years of age were identified as the key intervention targets in Guiyang based on the molecular transmission network. Patients should routinely undergo drug resistance testing before starting antiretroviral therapy to avoid virologic treatment failure and prevent the spread of HIV-1-resistant strains in MSM.

Pre- and Post-Exposure Prophylaxis for HIV in Patients Taking Anti-Seizure Medications.

The prevention of human immunodeficiency virus (HIV) infection has recently emphasized the use of pre- and post-exposure prophylaxis (PrEP and PEP), both of which were highly effective in prevention of HIV infection. Since the last published guidance regarding the cotreatment of people with anti-seizure medications (ASM) and antiretroviral treatments (ARTs) in 2012, both fields have numerous new medication options. Historically, cotreatment of HIV and seizures could be challenging with increased risk of virologic failure and barriers in access to health care due to global availability, social determinants of health, and stigma of both HIV and seizures. In this narrative review, we describe the data-driven and expected bidirectional pharmacokinetic (PK) interactions between guideline-based PrEP and PEP treatment and ASM, as well as overlapping side effects. There are many ASMs with no known interaction with PrEP or PEP regimens. The interactions focus on enzyme inducing ASMs, valproate, and lamotrigine. Most prominently, enzyme inducing ASMs lower serum levels of tenofovir-containing PrEP regimens and elements of PEP (dolutegravir, raltegravir, and ritonavir), which increased risk of virologic treatment failure in people with HIV but have unclear clinical significance on the effectiveness of PrEP and PEP. In addition, ritonavir treatment in PEP may significantly lower lamotrigine serum levels even during the 4 weeks of treatment, which may increase risk for breakthrough seizures during PEP and skin reactions after discontinuation of ritonavir. In addition to PK interactions, overlapping side effects are common including osteopenia, hepatic toxicity, and other gastrointestinal effects. This narrative review aims to be a resource for all clinicians prescribing ASMs so that they can create a welcoming environment to enable successful treatment of seizures and reduce the risk of HIV infection in people at risk. In addition, we highlight knowledge gaps and areas of unmet need that can be addressed with future studies.

Rare HCV subtypes and retreatment outcomes in a cohort of European DAA-experienced patients

Data on the prevalence and characteristics of so-called rare HCV genotypes (GTs) in larger cohorts is limited. This study investigates the frequency of rare GT and resistance-associated substitutions and the efficacy of retreatment in a European cohort. A total of 129 patients with rare GT1-6 were included from the European resistance database. NS3, NS5A, and NS5B were sequenced and clinical parameters and retreatment efficacies were collected retrospectively. Overall 1.5% (69/4,656) of direct-acting antiviral (DAA)-naive and 4.4% (60/1,376) of DAA-failure patients were infected with rare GT. Although rare GTs were almost equally distributed throughout GT1-6 in DAA-naive patients, we detected mainly rare GT4 (47%, 28/60 GT4; of these n= 17, subtype 4r) and GT3 (25%, 15/60 GT3, of these n= 8, subtype 3b) among DAA-failures. A total of 62% (37/60) of DAA failures had not responded to first-generation regimes and the majority was infected with rare GT4 (57%, 21/37). In contrast, among patients with failure to pangenotypic DAA regimens (38%, 23/60), infections with rare GT3 were overrepresented (57%, 13/23). Although NS5A RASs were uncommon in rare GT2, GT5a, and GT6, we observed combined RASs in rare GT1, GT3, and GT4 at positions 28, 30, 31, which can be considered as inherent. DAA failures with completed follow-up of retreatment, achieved a high SVR rate (94%, 45/48 modified intention-to-treat analysis; 92%, 45/49 intention-to-treat). Three patients with GT4f, 4r, or 3b, respectively, had virological treatment failure. In this European cohort, rare HCV GT were uncommon. Accumulation of specific rare GT in DAA-failure patients suggests reduced antiviral activities of DAA regimens. The limited global availability of pangenotypic regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed. Data on the prevalence and characteristics of rare HCV genotypes (GT) in larger cohorts are still scarce. This study found low rates of rare HCV GTs among European HCV-infected patients. In direct-acting antiviral (DAA)-failure patients, rare GT3 subtypes accumulated after pangenotypic DAA treatment and rare GT4 after first generation DAA failure and viral resistance was detected at NS5A positions 28, 30, and 31. The limited global availability of pangenotypic DAA regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed.

Antiretroviral treatment failure and associated factors among people living with HIV on therapy in Homa Bay, Kenya: A retrospective study.

Despite large numbers of patients accessing antiretroviral treatment (ART) in Kenya, few studies have explored factors associated with virologic failure in Western Kenya, specifically. We undertook a study in Homa Bay County, Kenya to assess the extent of virologic treatment failure and factors associated with it. This was an observational retrospective study conducted from September 2020 to January 2021. Data were abstracted from the records of patients who had been on ART for at least six months at the time of data collection after systematic sampling stratified by age group at ART initiation (0-14 and 15+ years), using probability proportion to the numbers of patients attending the facility. Confirmed viral treatment failure was defined as viral load ≥1000 copies/ml based on two consecutive viral load measurements after at least three months of enhanced adherence counseling. Data were analyzed using descriptive statistics and Cox regression modeling. Of the 2,007 patients sampled, 160 (8.0%) had confirmed virologic treatment failure. Significantly higher virologic treatment failure rates were identified among male patients 78/830 (9.4%) and children 115/782 (14.7%). Factors associated with virologic treatment failure (VTF), were age 0-14 years, adjusted hazard ratio (AHR) 4.42, (95% Confidence Interval [CI], 3.12, 6.32), experience of treatment side effects AHD: 2.43, (95% CI, 1.76, 3.37), attending level 2/3 health facility, AHR: 1.87, (95% CI: 1.29, 2,72), and history of opportunistic infections (OIs), AHR: 1.81, (95% CI, 1.76, 3.37). Children, attendees of level 2/3 health facilities, patients with a history of OIs, and those experiencing treatment side-effects are at risk of VTF. Increased focus on children and adolescents on screening for drug resistance, administration of and adherence to medication, and on effective information and education on side-effects is critical. Additionally, there is need for increased training and support for health care workers at primary level care facilities.

Determinants of virological failure among patients on first line highly active antiretroviral therapy (HAART) in Southwest Ethiopia: A case-control study.

Virological failure remains a public health concern among patients with human immunodeficiency virus (HIV) after treatment initiation. Ethiopia is one of the countries that aims to achieve the global target of 90-90-90 that aims to achieve 90% virological suppression, but there is a paucity of evidence on the determinants of virological failure. Therefore, the study is intended to assess determinants of virological treatment failure among patients on first-line highly active antiretroviral therapy (HAART) at Mizan Tepi University Teaching Hospital (MTUTH), Southwest Ethiopia. A hospital-based unmatched case-control study was conducted from 11 November to 23 December 2020, among 146 cases and 146 controls. All cases and controls were selected randomly using computer-generated random numbers based on their medical record numbers. During the document review, data were collected using checklists, entered into Epi-data version 4.0.2, and analyzed by SPSS version 25. A multivariable logistic regression analysis was done to identify the independent determinants of virological treatment failure. In this study, being male (adjusted odds ratio (AOR) = 1.89, 95% CI: 1.04, 3.47), substance use (AOR = 2.67, 95% CI: 1.40, 4.95), baseline hemoglobin (Hgb) < 12 mg/dl (AOR = 3.22, 95% CI: 1.82, 5.99), poor drug adherence (AOR = 3.84, 95% CI: 1.77, 5.95), restart ART medication (AOR = 2.45, 95% CI: 1.69, 7.35), and opportunistic infection (OI) while on HAART (AOR = 4.73, 95% CI: 1.76, 12.11) were determinants of virological treatment failure. The study revealed that the sex of the patient, history of substance use, baseline Hgb < 12 mg/dl, poor drug adherence, restart after an interruption, and having OI through the follow-up period were determinants of virological failure. Therefore, program implementation should consider gender disparity while men are more prone to virological failure. It is also imperative to implement targeted interventions to improve drug adherence and interruption problems in follow-up care. Moreover, patients with opportunistic infections and restart HAART need special care and attention.

Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure

Data on the long-term persistence of HCV resistance-associated substitutions (RASs) after treatment with direct acting antivirals (DAAs) are limited. This study evaluated the persistence of NS3, NS5A and NS5B RASs for up to 5 years after the end of treatment (EOT). We included samples from n=678 patients with a HCV GT (genotype) 1 or 3 infection and virologic DAA treatment failure collected in the European Resistance Database. NS3, NS5A and NS5B were sequenced and clinical parameters were evaluated. A total of 242 patients with HCV GT1a (36%), 237 with GT1b (35%) and 199 (29%) with GT3 and a DAA failure were included. After protease inhibitor failure, the frequencies of NS3 RASs were 40-90% after end of treatment (EOT) and RASs disappeared rapidly in GT1b and GT3 after follow-up month 3 (FU3), while in GT1a RASs were stable (≥ 60%) due to Q80K. The SOF-resistant NS5B RAS S282T was only found in individual GT3a patients. Non-nucleoside NS5B RASs were frequent in GT1 (56-80%) and decreased to 30% in GT1a but persisted in GT1b. NS5A RASs were very common in all GTs after NS5A inhibitor failure (88-95%), and even after FU24 their frequency was 65% and higher. However, RASs in GT1b had a stable course, while RASs in GT1a and GT3 declined slightly after FU24 (GT1a, 68%; GT1b, 95%; GT3, 65%), mainly due to the slow decline of high-level resistant Y93H. We found that low to medium-level RASs persisted, while high-level resistant RAS disappeared over time. Different patterns of RAS persistence according to HCV subtype could have implications for retreatment with first generation DAAs and for global HCV elimination goals. The long-term persistence of RASs after DAA failure is largely unknown. RASs in NS3 (with exception of Q80K) and S282T in NS5B generally declined rapidly. NS5A RASs persisted beyond two years after end of treatment, with a slight decrease in GT1a and GT3 compared to GT1b. The different patterns of RAS persistence could be of importance for re-treatment especially in countries with limited medical resources.

Determining the lower limit of detection required for HCV viral load assay for test of cure following direct-acting antiviral-based treatment regimens: Evidence from a global data set.

Achieving global elimination of hepatitis C virus requires a substantial scale‐up of testing. Point‐of‐care HCV viral load assays are available as an alternative to laboratory‐based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post‐treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical‐sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low‐level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170–276). Females and those with minimal fibrosis were more likely to experience low‐level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30–1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15–1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low‐level treatment failure.

Virological and Immunological Antiretroviral Treatment Failure and Predictors Among HIV Positive Adult and Adolescent Clients in Southeast Ethiopia.

BackgroundAntiretroviral therapy (ART) regimen failure is linked to an increased risk of disease progression and death, while early detection of ART failure can help to prevent the development of resistance. This study aimed to evaluate virological and immunological ART failure and predictors among HIV-positive adult and adolescent clients in southeast Ethiopia.MethodsA retrospective cohort study was implemented from January 2016 to November 30, 2020; all HIV-positive nave patients on follow-up during the study period from four hospitals were included. Virological and immunological treatment failure was the primary outcome of the study. Cox proportional hazards regression models were employed for analysis. Hazard ratios with 95% confidence intervals were reported and variables with p-values <0.05 were considered statistically significant predictors of treatment failure.ResultsA total of 641 HIV patients’ charts were reviewed, 62.6% of the study participants were females. Of the total study participants, 18.4% and 15% developed virological and immunological ART regimen treatment failure respectively. The median time to virological failure was 40 months. WHO stage IV [AHR = 4.616; 95% CI: (2.136–9.974)], WHO stage III [AHR = 2.323; 95% CI: (1.317–4.098)], poor adherence to HAART regimen [AHR = 3.097; 95% CI: (1.349–7.108)], and fair adherence [AHR = 2.058; 95% CI: (1.234–3.432)] were significantly associated with virological treatment failure among adolescent and adult study participants in southeast Ethiopia.ConclusionThe prevalence of virological treatment failure was 18.4% (95% CI: 15.4 −21.4) and the prevalence of immunological treatment failure was 15% (95% CI: 11.8–18.4). WHO clinical stage III/IV and non-adherence were independent predictors of virological ART treatment failure. Early management of clinical WHO stages and improving patients’ ART regimen adherence are important to decrease the prevalence of ART regimen treatment failure.

Durability of single tablet regimen for patients with HIV infection in Southern Taiwan: data from a real-world setting

BackgroundA single-tablet regimen (STR) has been associated with better drug adherence. However, the durability of different STRs was unknown in the real-world settings. Our aim was to investigate the durability of different initial STR regimens in antiretroviral-naive patients starting STR in southern Taiwan.MethodThis was a retrospective study of antiretroviral-naive patients that initiated first-line antiretroviral regimens with STRs between May 2016 and December 2017. The primary endpoint was time to virological failure. Secondary endpoints were STR discontinuation due to toxicity/intolerance. Durability was defined as time from the initiation until discontinuation/modification. Kaplan- Meier curves were plotted assessing time to virological suppression, treatment failure and discontinuation for the three STRs and Cox proportional hazards model was used to analyze the factors associated with time to viral suppression, treatment failure or discontinuation.ResultsTwo hundred and twenty-three patients were included: The median follow-up duration (IQR) was 73.9 (48–101.6) weeks, 25 patients (11%) experienced virological failure; the 48 weeks probability of treatment failure was 22.9% (16/70) for Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF), 24.1% (13/54) for Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF) and 24.2% (24/99) for Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC) (p=0.16). Fifty-six patients (25%) discontinued their STRs owing to toxicity/intolerance. When compared to EFV/FTC/TDF, treatment with FTC/RPV/TDF (aHR 8.39, CI 1.98–35.58, p = 0.004) and ABC/DTG/3TC (aHR 8.40, CI 2.39–29.54, p=0.001) were more likely to have treatment failure. The predictors for treatment failure included age ≦ 30 years old (aHR 3.73, CI 1.25–11.17, p = 0.018), switch between different STR (aHR 2.3, CI 1.18–4.50, p = 0.001) and free of active syphilis infection (aHR 0.24, CI 0.08–0.73, p = 0.012). The risk factor for treatment discontinuation included younger age ≦ 30 years old (aHR 3.82, CI 1.21–12.37, p = 0.023), treatment with EFV/FTC/TDF (aHR 8.65, CI 2.64–28.39, p < 0.001) and free of active syphilis infection (aHR 0.16, CI 0.04–0.62, p = 0.006).ConclusionYounger age was associated with treatment failure and drug discontinuation. Active syphilis infection s/p treatment was associated with free from treatment failure and discontinuation. This probably driven by the more frequently sexual health education and counseling when patients had syphilis infection. Treatment with ABC/DTG/3TC was associated with higher risk of treatment failure. The STR durability was dependent on the drug toxicity/intolerance, age and syphilis infection.

First-line virologic-based ART treatment failure and associated factors among adult HIV Positives in Southwest Shoa, Central Ethiopia.

Background: The function of antiretroviral therapy is to enhance immunity and prevent the occurrence of opportunistic infection. But antiretroviral therapy showed a failure to manage infection after a time. Nowadays, an accepted criterion to confirm Antiretroviral therapy (ART) treatment failure is a virologic failure. Regarding this virologic failure, there are no well-addressed findings, especially in this study area. Therefore in this research, the magnitude and factors that contribute for virological ART treatment failure have been identified. Methods: Facilitybased cross-sectional study was conducted on adult patients taking ART. Data entry was conducted using Epi Data Version3 and exported to Stata SE version 14 for analysis. Bivariable logistic regression was used to find covariates significantly associated with firs line ART treatment failure. In this case, variables with P-value ≤ .25 were a candidate for multiple logistic regressions. A backward logistic regression model was used. Finally, variables with P-value ≤ .05 were considered as factors significantly associated with first-line ART treatment failure and the result was presented with a description, graph, and tables. Results: In this study, three hundred and fifty peoples were a candidate for the study and all have been involved. The magnitude of first-line ART treatment failure based on virologic criteria was 20.85%. Greater than three-fourth (84.29%) of study participants have support from somebody. Those patients who have initiated first-line ART with NVP based regimen have 1.83 times more likely to face first-line ART treatment failure as compared with those who have started with Efeverence (EFV) based regimen [AOR = 1.83, 95% CI (1.035, 3.245)]. Patients who have initiated first-line ART at the health center were 3.093 times more likely to face first-line ART treatment failure as compared those who have initiated ART at hospitals [AOR = 3.093, 95% CI (1.101, 8.685)]. Patients who have not developed a common opportunistic infection after ART initiation was 47.3% less likely to encounter first-line ART treatment failure as compared with those who have opportunistic infection [AOR = 0.527, 95% CI (0.289, 0.961)]. Conclusion: Based on virologic criteria, NVP based ART initiation, having history recorded opportunistic infection after ART initiation, being male, Institution where initiate ART, are significantly associated with the occurrences of first-line ART treatment failure. The action has to be directed on those identified factors to maintain the patient stay on First-line ART by concerned stakeholders.

Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children

BackgroundChildren with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART).MethodsWe conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non–dolutegravir-based ART) in children and adolescents starting first- or second-line ART. The primary end point was the proportion of participants with virologic or clinical treatment failure by 96 weeks, as estimated by the Kaplan–Meier method. Safety was assessed.ResultsFrom September 2016 through June 2018, a total of 707 children and adolescents who weighed at least 14 kg were randomly assigned to receive dolutegravir-based ART (350 participants) or standard care (357). The median age was 12.2 years (range, 2.9 to 18.0), the median weight was 30.7 kg (range, 14.0 to 85.0), and 49% of the participants were girls. By design, 311 participants (44%) started first-line ART (with 92% of those in the standard-care group receiving efavirenz-based ART), and 396 (56%) started second-line ART (with 98% of those in the standard-care group receiving boosted protease inhibitor–based ART). The median follow-up was 142 weeks. By 96 weeks, 47 participants in the dolutegravir group and 75 in the standard-care group had treatment failure (estimated probability, 0.14 vs. 0.22; difference, –0.08; 95% confidence interval, −0.14 to −0.03; P=0.004). Treatment effects were similar with first- and second-line therapies (P=0.16 for heterogeneity). A total of 35 participants in the dolutegravir group and 40 in the standard-care group had at least one serious adverse event (P=0.53), and 73 and 86, respectively, had at least one adverse event of grade 3 or higher (P=0.24). At least one ART-modifying adverse event occurred in 5 participants in the dolutegravir group and in 17 in the standard-care group (P=0.01).ConclusionsIn this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.)

Rate and predictors of HIV virological failure among adults on first-line antiretroviral treatment in Dar Es Salaam, Tanzania.

Monitoring resistance to first line Antiretroviral therapy (ART) is crucial in preventing accumulation of viral mutations following the implementation of the World Health Organization "treat all" initiative. We estimated the rate and predictors of virological treatment failure among adults living with HIV/AIDS in Dar es Salaam, Tanzania. A retrospective cohort study involving adults aged 18 and above receiving first line ART in Dar as Salaam between 2016 and 2018 were recruited using multistage random sampling. Clinical and laboratory data were extracted from Care and Treatment Clinic database-2 (CTC2) followed by participant's interviews. Adjusted Cox-regression modelling was used to determine independent predictors of treatment failure. A total of 340 participants with mean age of 37 were recruited. Overall, 10.59% had virological failure and the rate of failure was 5.24 (95% CI:3.72; 7.27) per 100 person-months at risk with a median failure time of 18 months. Independent predictors of treatment failure were being a male (Adjusted hazard ratio (aHR) 2.78, 95%CI:1.16;6.63), having used treatment for less than two years (aHR, 12.48, 95%CI:3.64-22.71) and co-infection with Tuberculosis (aHR 2.1, 95%CI: 1.0;5.9). HIV virological failure occurs early during treatment in this population. Male clients, co-infected with Tuberculosis were at higher risk of ART failure within two years of treatment. Substantial stride has been made towards the achievement of the last UNAIDS 90 goal but tailored counseling and close monitoring of HIV/TB co-infected male clients following ART initiation could accelerate efforts to close the gap. Further studies on pre-treatment drug resistance mutations are called for.

Classification of HIV-1 virological treatment failure using the Roche cobas plasma separation card on cobas 8800 compared to dried blood spots on Abbott RealTime HIV-1

Measurement of HIV-1 viral load (VL) is essential for monitoring antiretroviral treatment (ART) efficacy. In remote settings, dried blood spots (DBS) may be used as the specimen type. However, cellular components in DBS not present in the gold standard specimen type, plasma, may result in low specificity i.e., over-estimation of VL results from DBS compared to plasma. The Abbott RealTime HIV-1 assay system has been reported to have improved specificity using DBS compared to other tests. A new specimen collection matrix, the cobas plasma separation card (PSC, Roche Molecular Systems), enables specimen collection from a finger prick or venous blood, using a multi-layer absorption and filtration design that results in a specimen similar to plasma. We performed a direct comparison between VL results from PSC tested with the cobas 6800/8800 assay (c8800) and DBS tested with the Abbott RealTime HIV-1 assay. Overall concordance between PSC and plasma around the 1000 copies/mL threshold was high (>97%). Compared to VL measured using DBS and the RealTime assay, PSC and c8800 showed improved sensitivity (96.9% vs 90.6%) and specificity (97.4% vs. 87.2%) using plasma as the reference, as there were fewer patients with VL below 1000 copies/mL in plasma in whom VL was over this threshold using PSC compared to DBS. The limit of detection for PSC was lower than for DBS (575 vs. 2314 copies/mL). cobas PSC represents a promising specimen type for use with the cobas 6600/8800 system in settings where plasma cannot be used.

Clinical, immunologic and virologic outcomes of children and adolescents receiving second line anti-retroviral therapy in two referral hospitals in Addis Ababa, Ethiopia.

BackgroundEthiopia launched free access for antiretroviral therapy in 2005. The number of patients on second line antiretroviral treatment has increased with each passing year. The objectives of this study were to describe the clinical, immunological and virologic outcomes of children and adolescents receiving second line anti-retroviral therapy in two referral hospitals, Yekatit 12 and Zewditu Memorial Hospitals, in Addis Ababa, Ethiopia.MethodsThis was a hospital based retrospective cohort study conducted among children and adolescents aged 18 years and less and receiving a second line antiretroviral drugs. Data was collected using structured questionnaires. Means and percentages were used for nominal variables. Statistical analysis was made using statistical software–SPSS 23.0. Kaplan Meier analysis, long rank test and multivariate Cox proportion model were used to identify factors affecting survival.ResultsA total of 75 children and adolescents were studied with a mean age of 13.28 years (SD: 4) with a mean treatment period on second line regimens of 35.2 months (SD: 21.8 months). Forty-eight participants were experiencing successful measures (in all three parameters) for their second line anti-retroviral treatment. Ten had virologic treatment failure while seven had died. Both treatment failure and death rates were higher within the first two years of treatment. Poor treatment adherence (Adjusted hazard ratio: 5.1 (95% CI: 1.1–23.2; p-value = 0.02)) and advanced World Health Organization clinical stage at start of the second line antiretrovirals (Adjusted hazard ratio: 7.51 (95% CI: 1.35–18.02; p-value = 0.002)) correlated significantly with survival of children and adolescents receiving treatment.ConclusionsThe study describes clinical, immunological and virologic outcomes of second line antiretroviral treatment in a pediatric cohort under care in two hospitals in Addis Ababa, Ethiopia. Poor adherence and pre-treatment advanced clinical stages were predictors of survival.

HIV Drug Resistance in Children and Adolescents: Always a Challenge?

Purpose of ReviewWith the expanded roll-out of antiretrovirals for treatment and prevention of HIV during the last decade, the emergence of HIV drug resistance (HIVDR) has become a growing challenge. This review provides an overview of the epidemiology and trajectory of HIVDR globally with an emphasis on pediatric and adolescent populations.Recent FindingsHIVDR is associated with suboptimal virologic suppression and treatment failure, leading to an increased risk of HIV transmission to uninfected people and increased morbidity and mortality among people living with HIV. High rates of HIVDR to non-nucleoside reverse transcriptase inhibitors globally are expected to decline with the introduction of the integrase strand transfer inhibitors and long-acting combination regimens, while challenge remains for HIVDR to other classes of antiretroviral drugs.SummaryWe highlight several solutions including increased HIV viral load monitoring, expanded HIVDR surveillance, and adopting antiretroviral regimens with a high-resistance barrier to decrease HIVDR. Implementation studies and programmatic changes are needed to determine the best approach to prevent and combat the development of HIVDR.

Detection of drug resistance mutations of hepatitis C virus in patients with failure of the treatment with direct acting antivirals

Background. The development of direct acting antivirals (DAAs) has spurred a revolution in treatment of patients with chronic hepatitis C. However, there are cases showing no response to treatment. In 5% of cases, the viral breakthrough is most likely caused by DAA resistance mutations in the hepatitis C virus genome.The purpose of the study is to detect drug resistance mutations of hepatitis C virus in patients with DAA treatment failure.Materials and methods. The study was performed on plasma samples from 3 patients diagnosed with chronic hepatitis C virus infection and demonstrating DAA virological treatment failure. All isolates had genotype 1b. Drug resistance mutations were detected by using direct sequencing of NS3, NS5A, and NS5B genome regions. The detection technique was developed at the Pasteur Research Institute of Epidemiology and Microbiology.Results. Drug resistance mutations were detected in all cases. By using the Geno2pheno [hcv] 0.92 tool, nucleotide substitutions were detected in different viral genome regions and presumably caused resistance or decreased sensitivity to antivirals both present and absent in the sofosbuvir + daclatasvir combination therapy. Antiviral treatment failure in patients with chronic hepatitis C is caused by drug resistance mutations.Conclusions. The developed technique is efficient for detection of drug resistance mutations in NS3, NS5A, and NS5B regions in cases of virological failure of DAA treatment.

Short Communication: Higher Tenofovir Concentrations in Hair Are Associated with Decreases in Viral Load and Not Self-Reported Adherence in HIV-Infected Adolescents with Second-Line Virological Treatment Failure.

Objective methods of measuring antiretroviral adherence are limited. We assessed the relationship between tenofovir disoproxil fumarate (TDF) hair concentrations, self-reported adherence, and virological outcomes in HIV-infected adolescents in Harare, Zimbabwe. HIV-infected adolescents on atazanavir/ritonavir-based second-line treatment for >6 months with viral load (VL) ≥1,000 copies/mL were randomized to either modified directly administered antiretroviral therapy (mDAART) or standard of care. Hair and VL samples were collected at baseline and after 90 days. Treatment outcome was defined as TDF concentrations in hair. Virological suppression was defined as VL <1,000 copies/mL. Thirty-four adolescents had TDF concentrations measured at baseline and follow-up. Mean (median); range age was 16 (16); 13-18 years and 53% were females. Nineteen (56%) were randomized to mDAART. Mean (SD); range TDF concentrations were 0.03 (0.04); 0-0.17 ng/mg hair and 0.06 (0.06); 0-0.3 ng/mg hair at baseline and follow-up, respectively. Higher TDF concentrations were associated with decreased VL [regression coefficient (RC) 0.8; 95% confidence interval (CI) 0.7-1.0; p = .008] and mDAART (RC 0.5; 95% CI 0.3-1.0; p = .04), but were not associated with self-reported adherence and virological suppression (VL <1,000 copies/mL). Higher TDF hair concentrations were observed with virological decrease and an adherence intervention. Hair antiretroviral concentrations could be useful in triggering adherence interventions among adolescents with second-line virological failure.

Incidence of Hepatotoxicity in Iranian Patients With HIV on Antiretroviral Therapies and Its Correlation with Virologic Response to HIV Treatment.

To investigate hepatotoxicity in Iranian patients with HIV to assess the association between virologic response to HIV treatment and serum alanine aminotransferase (ALT). This study was conducted with 200 control patients, 75 patients with HIV naïve to antiretroviral therapy (ART), and 443 patients who received ARTs with virologic response (≤1000 copies/mL) or virologic treatment failure (>1000 copies/mL). Serum ALT level and HIV viral load were determined in all patients. Patient ALT levels were significantly higher than those of control patients (45.1 ± 44.4 IU/L vs 23.8 ± 5.4 IU/L). Compared to patients who were ART-naïve, patients with ART experience had significantly higher ALT levels (38.2 ± 26.2 IU/L vs 46.3 ± 46.7 IU/L), and severe hepatotoxicity was only detected in those with ART experience (8 patients, 1.8%). Mean ALT had no significant difference between virologic response/failure groups. The ALT activity and HIV load had a negative correlation coefficient, but it was not significant. Periodic monitoring for the possibility of hepatotoxicity is highly recommended in all patients with HIV, especially in those receiving ART treatment.

Virological Treatment Failure Among Adult HIV/AIDS Patients from Selected Hospitals of North Shoa Zone, Amhara Region, Ethiopia.

PurposeThe study aimed at assessing the magnitude of virological treatment failure and associated factors among HIV reactive adults at selected hospitals.Patients and MethodsA facility-based cross-sectional study was conducted among 498 study participants who started their first-line HAART from August 2015 to December 2018. Data were collected from patients’ charts and face-to-face interviews using a structured questionnaire. The bivariable analysis was executed to select candidate variables at a p-value of less than 0.2. Multivariable logistic regression (forward, stepwise, and conditional) analysis was used to find factors associated with virological failure at a significant level of 5%. A model adequacy check was done by Hosmer and Lemeshow test (p = 0.57).ResultsMore than half 290 (58.2%) of the study participants were women. The median (IQR) age at ART initiation was 40 (15) years. The median (IQR) duration when a virological failure occurred from the initiation of ART treatment was 96 (72) months. The prevalence of virological treatment failure was 10.24% (95% CI: 7.57%, 12.91%). Poor ART drug adherence (AOR = 4.54; 95% CI: 2.09, 9.87), CD4 count less than 250 cell/μL (AOR = 24.88; 95% CI: 11.73, 52.81) and poor quality of life (QoL) (AOR = 2.65; 95% CI: 1.12, 6.25) were independent predictors of virological treatment failure.ConclusionThe magnitude of virological ART treatment failure in this study was relatively high. Poor ART drug adherence, patients’ having lower CD4 count and poorer quality of life were predictors of treatment failure. Thus, intervention programs that enrich patients’ health-related quality of life should be implemented. Moreover, counseling that supplements the importance of drug adherence and reduction of risks that lower CD4 counts should be given emphasis which in turn helps to prevent first-line ART treatment failure.

S1063 Factors Predicting Failure of Hepatitis C Therapy in a Diverse Urban Population

INTRODUCTION: Hepatitis C therapy failure is a rare event and it is important to continue to assess reasons for therapy failure in a real-world population. We evaluated the therapy failure rates and reasons for failure in a diverse urban population. METHODS: We evaluated all patients with initiation of therapy for hepatitis C at a single urban hospital between October 2014 and January 2018. Patients were excluded if they had incomplete laboratory data. The population was analyzed based on achieving sustained virologic response (SVR) versus treatment failure. Data analyzed included treatment regimens, viral genotype, cirrhosis status, and transplant status. RESULTS: 1680 patients had initiation of hepatitis C antiviral therapy between October 2014 and January 2018. The antiviral treatments groups studied were ledipasvir/sofosbuvir (79%), sofosbuvir/velpatasvir (8.3%), elbasvir/grazoprevir (7%), glecaprevir/pibrentasvir (4%), sofosbuvir/velpatasvir/voxilaprevir (1.5%), and other therapies including ombitasvir/paritaprevir/ritonavir and ombitasvir/paritaprevir/ritonavir/dasabuvir (0.4%). These therapies were either given alone or in combination with ribavirin (RBV). 33.5% of these patients were treatment-experienced. 36.8% had established cirrhosis and 8.2% had a history of liver transplant. Overall the SVR rate was 95.6%. The SVR rate for each treatment group was 95.4% for ledipasvir/sofosbuvir +/- RBV, 94.2% for sofosbuvir/velpatasvir +/- RBV, 96.7% for elbasvir/grazoprevir +/- RBV, 100% for glecaprevir/pibrentasvir, and 96% for sofosbuvir/velpatasvir/voxilaprevir +/- RBV. There was no statistically significant difference in SVR rate between the treatment groups (P = 0.502). The SVR rate in those with cirrhosis was 93% compared to 97% in those without cirrhosis (P < 0.001). Additionally, patients who required ribavirin in certain combination therapies had a lower likelihood of achieving SVR with SVR of 80% with elbasvir/grazoprevir/RBV compared to 98.2% with elbasvir/grazoprevir alone (P = 0.023). CONCLUSION: There is no difference in achieving SVR based on the treatment chosen. However, patients diagnosed with liver cirrhosis or those who required ribavirin supplementation by clinical standards in certain combination therapies were noted to have SVR failure more frequently.Table 1.: Hepatitis C therapy, viral genotype, known cirrhosis, and liver transplant in SVR success and failure groups