ART-experienced Patients Research Articles

HIV-1 Drug Resistance Mutations among Antiretroviral Drug-Experienced Patients in the South of Iran

Background: The therapeutic effect of antiretroviral therapy (ART) is adversely influenced by antiretroviral drug resistance, mainly due to mutations (DRMs) in the human immunodeficiency virus (HIV) genome. These mutations are commonly associated with HIV protease and reverse-transcriptase genes. We sought to determine the frequency of DRMs in a population of ART-experienced patients in the South of Iran. Method: A total of 44 HIV-1-positive participants under ART were selected from April 2016 to March 2017. Their DRMs, antiretroviral resistance status, and viral subtypes were determined. Results: At least one DRM was detected in 61.4% of the participants. The highest frequency was related to nucleotide reverse-transcriptase inhibitor (NRTI) mutations (45.45%). In contrast, major protease inhibitor (PI) mutations had the lowest frequency (6.81%). M184V (40.9%) and K103N (25%), respectively related to NRTI and nonnucleoside reverse-transcriptase inhibitor (NNRTI), were the mutations with the highest frequencies. Susceptibility to PI drugs was higher compared to NRTIs and NNRTIs, which was consistent with the results of genotypic DRMs. Conclusion: The highest frequency of antiretroviral DRMs was related to NRTIs and NNRTIs. In contrast, PI resistance mutations had the lowest frequency. Laboratory-guided ART to avoid the expansion of mutants as well as investigating DRMs in other viral regions, such as integrase, are recommended.

557. Evaluation of Clinical Response of a Two Tablet Once Daily Antiretroviral Regimen in Antiretroviral Experienced HIV-Infected Patients

BackgroundThe benefits of antiretroviral therapy (ART) are compromised by virologic failure and drug resistance. To maintain virologic suppression, these patients have traditionally required multitablet “salvage” regimens. We retrospectively analyzed data to assess virologic efficacy of a two-tablet, once daily combination of Elvitegravir/Cobicistat/Emtricitabine/TAF plus Darunavir (G/D) in HIV-infected adults with history of prior resistance and regimen failure.MethodsElectronic Medical Records of HIV-infected adults with history of prior resistance and regimen failure in our HIV-Clinic were analyzed to assess efficacy of a two-tablet ART regimen of G/D. Efficacy was defined as percentage of participants with HIV-1 RNA <50 copies/mL. Statistical analysis included descriptive summary of all patients. Categorical variables (gender, mode of transmission, the presence of undetected viral load, the presence of viral load <50, class resistance number, and the presence of M184V mutation) were compared between the two outcome groups (success vs. failure) using the Fisher exact test. The two groups were also compared using Student’s two-sample t-test for normally distributed numerical variables (age and number of years from diagnosis to regimen change) and the Wilcoxon rank-sum test for non-normally distributed numerical variables (CD4 level at diagnosis and CD4 level at regimen change).ResultsThirty-four patients were included in the study, of which 70.6% were men, majority MSM: 64.7%. Patients had been diagnosed with HIV for a median of 13.8 ± 7.3 years. More than 50% of patients at time of switch were on four pills and 53% were on a BID regimen. 61.7% patients were virologically suppressed with the regimen of G/D. There was no difference between virologic success vs. failure group when following variables were compared: CD4 at the time of regimen change, undetectable HIV VL vs. viremic patients at regimen change, the number of drug class resistance, the presence of M184 V mutation. Only statistically significant variable was age, virologic failure arm patients were younger; 35.8 vs. 48.2 years.ConclusionDespite the small numbers of patients, our results demonstrate that in a clinical setting a two tablet regimen provides substantial efficacy in ART-experienced patients harboring resistant virus.Disclosures I. Brar, Gilead: Research Contractor and Speaker’s Bureau, Research grant and Speaker honorarium. Janssen: Research Contractor and Speaker’s Bureau, Research grant and Speaker honorarium. Viiv: Research Contractor, Research grant.

Integrase Strand Transfer Inhibitor Resistance Mutations in Antiretroviral Therapy-Naive and Treatment-Experienced HIV Patients in South Korea.

Updated guidelines for the treatment of antiretroviral therapy (ART)-negative patients with HIV recommend integrase strand transfer inhibitor (INSTI)-based regimens. HIV patients are tested for resistance to antiretrovirals, and the reported prevalence of transmitted INSTI resistance remains rare worldwide. However, no data related to INSTI resistance in Korean HIV patients have been reported. We aimed to determine the prevalence of INSTI resistance-related mutations in South Korea. We subjected both ART-naive (n = 58) and ART-experienced Korean HIV patients (n = 41) to genotypic resistance analysis and determined a prevalence of INSTI major resistance mutations of 3.4% (n = 2) among ART-naive patients and 22.0% (n = 9) among ART-experienced patients. In the former group, both major INSTI resistance cases involved the nonpolymorphic E92Q mutation in the integrase strand. Our findings suggest that INSTI resistance testing should be included in the standard resistance screening protocols for Korean HIV patients.

Effectiveness of a multivitamin supplementation program among HIV-infected adults in Tanzania

The objective of this study was to assess the effectiveness of a routine multivitamin supplementation program for adults living with HIV in Tanzania. We conducted a retrospective cohort study of 67 707 adults enrolled in the Dar es Salaam HIV care and treatment program during 2004-2012. The Dar es Salaam HIV care and treatment program intended to provide all adult patients with multivitamin supplements (vitamins B-complex, C, and E) free of charge; however, intermittent stockouts and other implementation issues did not afford universal coverage. We use Cox proportional hazard models to assess the time-varying association of multivitamin supplementation with mortality and clinical outcomes. The study cohort contributed 41 540 and 129 315 person-years of follow-up time to the antiretroviral therapy (ART)-naive and ART-experienced analyses, respectively. Among 48 207 ART-naive adults, provision of multivitamins reduced the risk of mortality [adjusted hazard ratio (aHR): 0.69; 95% confidence interval (CI): 0.59-0.81], incident tuberculosis (TB) (aHR: 0.83; 0.76-0.91), and meeting ART eligibility criteria (aHR: 0.78; 95% CI: 0.73-0.83) after adjustment for time-varying confounding. Among 46 977 ART-experienced patients, multivitamins reduced mortality (hazard ratio: 0.86; 95% CI: 0.80-0.92), incident TB (aHR: 0.78; 95% CI: 0.73-0.84), and immunologic failure (aHR: 0.70; 95% CI: 0.67-0.73). The survival benefits associated with provision multivitamins appeared to be greatest during the first year of ART and declined over time (P value <0.001). Multivitamin supplementation appears to be a simple, effective, safe, and scalable program to improve survival, reduce incidence of TB, and improve treatment outcomes for adult HIV patients in Tanzania.

High frequency of drug resistance mutations in the HBV genome in ART-experienced HIV-coinfected patients in southwestern Nigeria.

HBV and HIV infections are highly endemic in sub-Saharan Africa and Nigeria while HBV-HIV coinfection is not uncommon. Antiretroviral (ART)-treatment for HIV can affect HBV whereby antiviral resistance mutations in the HBV genome can be selected. Here, we determined the prevalence of resistance mutations among ART-experienced and ART-naive HIV-HBV-coinfected patients in southwestern Nigeria. A total of 81 serum samples from HBV-HIV-coinfected patients who were either ART-naive or received lamivudine (3TC)-containing ART-therapy and HBV-monoinfected patients were analysed. Hepatitis B surface antigen (HBsAg) was detected using ELISA. HBV-positive samples were confirmed by PCR amplification of the surface and polymerase regions. Mutations conferring drug resistance to HBV were analysed by direct sequencing. Phylogenetic analysis was performed to identify the HBV genotype. Of the 81 HBsAg-positive samples, 27 had detectable HBV DNA by real-time PCR with mean viral loads of 6.77 log IU/ml. Phylogenetic analyses showed a predominance of HBV genotype E. A high prevalence (22.2%; 6/27) of HBV resistance mutations among ART-experienced HBV-HIV-coinfected patients was detected. However, a relatively high selection rate of resistance mutations in drug-naive HIV-HBV-coinfected (3.7%; 1/27) and in HBV-monoinfected patients, potential drug resistance mutations (7.4%; 2/27) were also observed. HBV polymerase amino acid substitutions found included rtV173L, rtL180M, rtM204V, rtK212R, rtS213T, rtV214A, rtL229V and rtP237A/S. Drug resistant mutations were detected frequently in ART-experienced HIV-HBV patients. Well-coordinated antiviral therapy for HIV patients coinfected with HBV should include proper HBV diagnosis and resistance testing to minimize the emergence and spread of antiviral drug resistance.

Trends, treatment outcomes, and determinants for attrition among adult patients in care at a large tertiary HIV clinic in Nairobi, Kenya: a 2004-2015 retrospective cohort study.

BackgroundUnderstanding trends in patient profiles and identifying predictors for adverse outcomes are key to improving the effectiveness of HIV care and treatment programs. Previous work in Kenya has documented findings from a rural setting. This paper describes trends in demographic and clinical characteristics of antiretroviral therapy (ART) treatment cohorts at a large urban, referral HIV clinic and explores treatment outcomes and factors associated with attrition during 12 years of follow-up.MethodsThis was a retrospective cohort analysis of HIV-infected adults who started ART between January 1, 2004, and September 30, 2015. ART-experienced patients and those with missing data were excluded. The Cochran–Armitage test was used to determine trends in baseline characteristics over time. Cox proportional hazards models were used to determine the effect of baseline characteristics on attrition.ResultsART uptake among older adolescents (15–19 years), youth, and young adults increased over time (p=0.0001). Independent predictors for attrition included (adjusted hazard ratio [95% CI]) male sex: 1.30 (1.16–1.45), p=0.0001; age: 15–19 years: 1.83 (1.26–2.66), p=0.0014; 20–24 years: 1.93 (1.52–2.44), p=0.0001; and 25–29 years: 1.31 (1.11–1.54), p=0.0012; marital status – single: 1.27 (1.11–1.44), p=0.0005; and divorced/separated: 1.56 (1.30–1.87), p=0.0001; urban residence: 1.40 (1.20–1.64), p=0.0001; entry into HIV care following hospitalization: 1.31 (1.10–1.57), p=0.0026, or transfer from another facility: 1.60 (1.26–2.04), p=0.0001; initiation of ART more than 12 months after the date of HIV diagnosis: 1.36 (1.19–1.55), p=0.0001, and history of a current or past opportunistic infection (OI): 1.15 (1.02–1.30), p=0.0284.ConclusionAlthough ART uptake among adolescents and young people increased over time, this group was at increased risk for attrition. Single marital status, urban residence, history of hospitalization or OI, and delayed initiation of ART also predicted attrition. This calls for focused evidence-informed strategies to address attrition and improve outcomes.

Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data

BackgroundThe prevalence of HIV-1 resistance to antiretroviral therapies (ART) has declined in high-income countries over recent years, but drug resistance remains a substantial concern in many low and middle-income countries. The Q151M and T69 insertion (T69i) resistance mutations in the viral reverse transcriptase gene can reduce susceptibility to all nucleoside/tide analogue reverse transcriptase inhibitors, motivating the present study to investigate the risk factors and outcomes associated with these mutations.MethodsWe considered all data in the UK HIV Drug Resistance Database for blood samples obtained in the period 1997–2014. Where available, treatment history and patient outcomes were obtained through linkage to the UK Collaborative HIV Cohort study. A matched case–control approach was used to assess risk factors associated with the appearance of each of the mutations in ART-experienced patients, and survival analysis was used to investigate factors associated with viral suppression. A further analysis using matched controls was performed to investigate the impact of each mutation on survival.ResultsA total of 180 patients with Q151M mutation and 85 with T69i mutation were identified, almost entirely from before 2006. Occurrence of both the Q151M and T69i mutations was strongly associated with cumulative period of virological failure while on ART, and for Q151M there was a particular positive association with use of stavudine and negative association with use of boosted-protease inhibitors. Subsequent viral suppression was negatively associated with viral load at sequencing for both mutations, and for Q151M we found a negative association with didanosine use but a positive association with boosted-protease inhibitor use. The results obtained in these analyses were also consistent with potentially large associations with other drugs. Analyses were inconclusive regarding associations between the mutations and mortality, but mortality was high for patients with low CD4 at detection.ConclusionsThe Q151M and T69i resistance mutations are now very rare in the UK. Our results suggest that good outcomes are possible for people with these mutations. However, in this historic sample, viral load and CD4 at detection were important factors in determining prognosis.

Efficacy and safety of boosted darunavir-based antiretroviral therapy in HIV-1-positive patients: results from a meta-analysis of clinical trials

Darunavir/ritonavir (DRV/r) is a second-generation protease inhibitor used in treatment-naïve and -experienced HIV-positive adult patients. To evaluate efficacy and safety in these patient settings, we performed a meta-analysis of randomized controlled trials. We considered eight studies involving 4240 antiretroviral treatment (ART)-naïve patients and 14 studies involving 2684 ART-experienced patients. Regarding efficacy in the ART-naive patients, the virological response rate was not significantly different between DRV/r and the comparator. For the ART-experienced failing patients, the virological response rate was significantly higher with DRV/r than with the comparator (RR 1.45, 95% CI: 1.01–2.08); conversely, no significant differences were found between the treatment-experienced and virologically controlled DRV/r and comparator groups. Regarding safety, the discontinuation rates due to adverse events (AEs) and DRV/r-related serious adverse events (SAEs) did not significantly differ from the rates in the comparator group (RR 0.84, 95% CI: 0.59–1.19 and RR 0.78, 95% CI: 0.57–1.05, respectively). Our meta-analysis indicated that DRV/r-based regimens were effective and tolerable for both types of patients, which was consistent with published data.

Inpatient mortality rates during an era of increased access to HIV testing and ART: A prospective observational study in Lilongwe, Malawi.

BackgroundIn the era of increased access to HIV testing and antiretroviral treatment (ART), the impact of HIV and ART status on inpatient mortality in Malawi is unknown.MethodsWe prospectively followed adult inpatients at Kamuzu Central Hospital medical wards in Lilongwe, Malawi, between 2011 and 2012, to evaluate causes of mortality, and the impact of HIV and ART status on mortality. We divided the study population into five categories: HIV-negative, new HIV-positive, ART-naïve patients, new ART-initiators, and ART-experienced. We used multivariate binomial regression models to compare risk of death between categories.ResultsAmong 2911 admitted patients the mean age was 38.5 years, and 50% were women. Eighty-one percent (81%) of patients had a known HIV status at the time of discharge or death. Mortality was 19.4% and varied between 13.9% (HIV-negative patients) and 32.9% (HIV-positive patients on ART ≤1 year). In multivariable analyses adjusted for age, sex and leading causes of mortality, being new HIV-positive (RR = 1.64 95% CI: 1.16–2.32), ART-naive (RR = 2.28 95% CI: 1.66–2.32) or being a new ART-initiator (RR = 2.41 95% CI: 1.85–3.14) were associated with elevated risk of mortality compared to HIV-negative patients. ART-experienced patients had comparable mortality (RR = 1.33 95% CI: 0.94–1.88) to HIV-negative patients.ConclusionHIV related mortality remains high among medical inpatients, especially among HIV-positive patients who recently initiated ART or have not started ART yet.

Antiretroviral treatment Long-Term (ALT) cohort: a prospective cohort of 10 years of ART-experienced patients in Uganda

PurposeLittle information is available on patients on antiretroviral treatment (ART) after a long-term period from sub-Saharan Africa, with the longest follow-up and related outcomes being after 10 years on ART....

Inflammatory Markers and Plasma Lipids in HIV Patients: A Correlation Analysis Study.

Background:Recent evidence suggests that HIV infection, even with treatment, increases the risk of coronary heart disease (CHD) and that both chronic inflammation and traditional risk factors play key roles in HIV-associated CHD.Subjects and Methods:Patients (N=152), attending Harare HIV clinic, 26% of them male and 82% of them on antiretroviral therapy (ART), were studied. Inflammatory markers comprising of cytokines such as pro-inflammatory tumor necrosis factor-α, (TNF-α), anti-inflammatory interleukin 10, (IL-10) and highly sensitive C reactive protein (hsCRP) together with lipids were assayed using enzyme linked immunosorbent assay (ELISA), immuno-turbidimetric and enzymatic assays, respectively. Correlation analysis of inflammatory markers versus lipid profiles was carried out using bivariate regression analysis.Results:Anti-inflammatory cytokine IL-10 and inflammatory hsCRP levels were elevated when measured in all the HIV positive patients, while TNF-α and lipid levels were within normal ranges. Pro-inflammatory TNF-α was significantly higher in ART-naive patients than ART-experienced patients, whereas the reverse was observed for anti-inflammatory IL-10 and anti-atherogenic HDL-C. Correlation analysis indicated a significant positive linear association between IL-10 and total cholesterol (TC) levels but no other correlations were found.Conclusion:High cytokine ratio (TNF-α/IL-10) indicates higher CHD risk in ART-naive patients compared to the ART-exposed. The CHD risk could be further strengthened by interplay between inflammatory markers and high prevalence of low HDL-C. Lack of correlation between pro-inflammatory markers (hsCRP and TNF-α) with lipid fractions and correlation between anti-inflammatory IL-10 with artherogenic TC were unexpected findings, necessitating further studies in future.

Dynamic HIV-1 genetic recombination and genotypic drug resistance among treatment-experienced adults in northern Ghana.

There have been hardly any reports on the human immunodeficiency virus type 1 (HIV-1) drug-resistance profile from northern Ghana since antiretroviral therapy (ART) was introduced over a decade ago. This study investigated prevailing HIV-1 subtypes and examined the occurrence of drug resistance in ART-experienced patients in Tamale, the capital of the Northern Region of Ghana. A cross-sectional study was carried out on HIV-infected adult patients receiving first-line ART. HIV viral load (VL) and CD4+ T-cell counts were measured. The pol gene sequences were analysed for genotypic resistance by an in-house HIV-1 drug-resistance test; the prevailing HIV-1 subtypes were analysed in detail.Results/Key findings. A total of 33 subjects were studied. Participants comprised 11 males (33.3 %) and 22 (66.7 %) females, with a median age of 34.5 years [interquartile range (IQR) 30.0-40.3]. The median duration on ART was 12 months (IQR 8.0-24). Of the 24 subjects successfully genotyped, 10 (41.7 %) viruses possessed at least one mutation conferring resistance to nucleoside or non-nucleoside reverse-transcriptase inhibitors (NRTIs/NNRTIs). Two-class drug resistance to NRTI and NNRTI was mostly detected (25 %, 6/24). The most frequent mutations were lamivudine-resistance M184V and efavirenz/nevirapine-resistance K103N. HIV-1 subtype CRF02_AG was predominant (79.2 %). Other HIV-1 subtypes detected were G (8.3 %), A3 (4.2 %) and importantly two (8.3 %) unique HIV-1 recombinant forms with CRF02_AG/A3 mosaic. HIV-1 shows high genetic diversity and on-going viral genetic recombination in the study region. Nearly 42 % of the patients studied harboured a drug-resistant virus. The study underscores the need for continued surveillance of HIV-1 subtype diversity; and of drug-resistance patterns to guide selection of second-line regimens in northern Ghana.

Cross-sectional comparative study of risky sexual behaviours among HIV-infected persons initiated and waiting to start antiretroviral therapy in rural Rakai, Uganda

ObjectivesTo compare risky sexual behaviours between HIV-positive persons initiated on antiretroviral therapy (ART) (ART-experienced) and persons waiting to start on ART (ART-naive) and assess predictors of risky sexual behaviours among...

Changes in coronary heart disease risk profiles of HIV patients in Zimbabwe over 9 months: a follow-up study.

Dyslipidemia, hypertension, inflammation, and coronary heart disease (CHD) are adverse events in human immunodeficiency virus (HIV)-infected patients even if they are receiving antiretroviral therapy (ART). Yet, data on CHD risk induced by HIV or ART in sub-Saharan Africa are limited. The aim of this longitudinal study was to describe changes in CHD risk profiles measured by lipids, inflammatory markers, and Framingham scores among HIV-positive patients previously reported from Harare, Zimbabwe. Patients were grouped into ART-experienced patients (n=147) and ART-naïve patients (n=23) and followed up for 9 months. Generalized least squares random-effects modeling was applied to explain changes in total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein, TC/HDL ratio, myeloperoxidase, highly sensitive C-reactive protein, and Framingham scores over the 9-month period. Independent variables included age, sex, monthly earning, body mass index, systolic blood pressure (SBP), diastolic blood pressure, duration of HIV diagnosis, duration of ART, viral load, and CD4 count. In ART-experienced patients, there was a substantial decrease in TC over time, ART-negative patients showed a significant increase in TC and HDL over time, and the increase in TC was associated with high viral load and low duration of HIV diagnosis, while increase in HDL was associated with young age, low body mass index, and low SBP. Framingham risk scores increased with time in ART-positive patients, and the change was positively correlated with age, sex, high SBP, and low HDL. There was no association between calculated CHD risk (TC/HDL ratio or Framingham score) and changes in levels of inflammatory markers (myeloperoxidase and highly sensitive C-reactive protein) in any of the patient groups. In conclusion, ART-experienced HIV-positive patients show changes in lipid values over time that makes it necessary to include lipid monitoring in order to reduce any risk of long-term CHD.

Antiretroviral drug resistance mutations in naïve and experienced patients in Shiraz, Iran, 2014.

Resistance to antiretroviral agents is a significant concern in the clinical management of HIV-infected individuals, particularly in areas of the world where treatment options are limited. In this study, we aimed to identify HIV drug-resistance-associated mutations in 40 drug-naïve patients and 62 patients under antiretroviral therapy (ART) referred to the Shiraz HIV/AIDS Research Center - the first such data available for the south of Iran. HIV reverse transcriptase and protease genes were amplified and sequenced to determine subtypes and antiretroviral- resistance-associated mutations (RAMs). Subtype CRF35-AD recombinant was the most prevalent in all patients (98 of 102, 96%), followed by subtype A1, and subtype B (one each, 2%). Among the 40 ART-naïve patients, two mutations associated with nucleoside reverse transcriptase inhibitor (NRTI) resistance (two with Y115F and T215I) and three associated with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (two with G190S and Y181C, four with V179T) were found. Among ART-experienced patients, four mutations associated with resistance to NRTI, four with NNRTI, and five with protease inhibitors (PI) were found. Twenty patients with high levels of resistance were already on second-line therapy. We document for the first time in this region of Iran high levels of ART resistance to multiple drugs. Our findings call for more vigilant systematic ART resistance surveillance, increased resistance testing, careful management of patients with existing regimens, and strong advocacy for expansion of available drugs in Iran.

Integrase Strand Transfer Inhibitors (INSTIs) Resistance Mutations in HIV-1 Infected Turkish Patients

Objectives: Integrase strand transfer inhibitor (INSTI) is a new class of antiretroviral (ARV) drugs designed to block the action of the integrase viral enzyme, which is responsible for insertation of the HIV-1 genome into the host DNA. The aim of this study was to evaluate for the first time INSTI resistance mutations in Turkish patients.Methods: This study was conducted in Turkey, between April 2013 and April 2015 using 169 HIV-1-infected patients (78 ARV naive patients and 91 ARV-experienced patients). Laboratory and clinical characteristics of ARV naive and ARV-experienced patients were as follows: gender (M/F): 71/7 and 80/11, median age: 38 and 38.4; median CD4+ T-cell: 236 and 216 cells/mm3, median HIV-1 RNA: 4.95+E5 and 1.08E+6 copies/ml. Population-based seqeunces of the reverse transcriptase, protease, and integrase domains of the HIV-1 pol gene were used to detect HIV-1 drug resistance mutations.Result: INSTI resistance mutations were not found in recently diagnosed HIV-1-infected patients. However, ARV-experienced patients had major resistance mutations associated with raltegravir and elvitegravir; the following results were generated:F121Y, Y143R, Q148R and E157Q (6/91 – 6.6%).Conclusions: The prevalence of INSTI resistant mutations in ART-experienced patients suggested that resistance testing must be incorporated as an integral part of HIV management with INSTI therapies.

Emergence of Acquired HIV-1 Drug Resistance Almost Stopped in Switzerland: A 15-Year Prospective Cohort Analysis.

Drug resistance is a major barrier to successful antiretroviral treatment (ART). Therefore, it is important to monitor time trends at a population level. We included 11 084 ART-experienced patients from the Swiss HIV Cohort Study (SHCS) between 1999 and 2013. The SHCS is highly representative and includes 72% of patients receiving ART in Switzerland. Drug resistance was defined as the presence of ≥1 major mutation in a genotypic resistance test. To estimate the prevalence of drug resistance, data for patients with no resistance test was imputed based on the patient's risk of harboring drug-resistant viruses. The emergence of new drug resistance mutations declined dramatically from 401 to 23 patients between 1999 and 2013. The upper estimated prevalence limit of drug resistance among ART-experienced patients decreased from 57.0% in 1999 to 37.1% in 2013. The prevalence of 3-class resistance decreased from 9.0% to 4.4% and was always <0.4% for patients who initiated ART after 2006. Most patients actively participating in the SHCS in 2013 with drug-resistant viruses initiated ART before 1999 (59.8%). Nevertheless, in 2013, 94.5% of patients who initiated ART before 1999 had good remaining treatment options based on Stanford algorithm. Human immunodeficiency virus type 1 drug resistance among ART-experienced patients in Switzerland is a well-controlled relic from the era before combination ART. Emergence of drug resistance can be virtually stopped with new potent therapies and close monitoring.

HIV Drug Resistance Mutations (DRMs) Detected by Deep Sequencing in Virologic Failure Subjects on Therapy from Hunan Province, China.

ObjectiveDetermine HIV drug resistance mutations (DRMs) prevalence at low and high levels in ART-experienced patients experiencing virologic failure (VF).Methods29 subjects from 18 counties in Hunan Province that experienced VF were evaluated for the prevalence of DRMs (Stanford DRMs with an algorithm value ≥15, include low-, intermediate and high-level resistance) by both Sanger sequencing (SS) and deep sequencing (DS) to 1% frequency levels.ResultsDS was performed on samples from 29 ART-experienced subjects; the median viral load 4.95×104 c/ml; 82.76% subtype CRF01_AE. 58 DRMs were detected by DS. 18 DRMs were detected by SS. Of the 58 mutations detected by DS, 40 were at levels <20% frequency (26 NNRTI, 12 NRTI and 2 PI) and the majority of these 95.00% (38/40) were not detected by standard genotyping. Of these 40 low-level DRMs, 16 (40%) were detected at frequency levels of 1–4% and 24 (60%) at levels of 5–19%. SS detected 15 of 17 (88.24%) DRMs at levels ≥ 20% that were detected by DS. The only variable associated with the detection of DRMs by DS was ART adherence (missed doses in the prior 7 days); all patients that reported missing a dose in the last 7 days had DRMs detected by DS.ConclusionsDS of VF samples from treatment experienced subjects infected with primarily AE subtype frequently identified Stanford HIVdb NRTI and NNRTI resistance mutations with an algorithm value 15. Low frequency level resistant variants detected by DS were frequently missed by standard genotyping in VF specimens from antiretroviral-experienced subjects.

Long-term efficacy and safety of etravirine-containing regimens in a real-life cohort of treatment-experienced HIV-1-infected patients

Objectives Etravirine (ETR) was approved in France in September 2008 and is used in combination with a boosted protease inhibitor (bPI) and other anti-retrovirals (ART) in HIV-infected pre-treated patients. This study aimed to report in a real-life setting the efficacy and tolerability of ETR-based regimens and factors associated with virological response. Methods The study population included all treatment-experienced patients who initiated an ETR-based regimen between September 2008 and July 2013 from the French Dat’AIDS cohort. Analyses were performed in ART-experienced patients starting ETR after virological failure (VF) or as a maintenance therapy (MT), with or without bPI. Results A total of 2006 patients (VF, n = 1014 (51%); MT, n = 992 (49%)) were included. At M12, the proportion of patients with HIV RNA < 50 copies/ml was 71.7% (72.0% and 71.1% with or without bPI) in the VF group and 90.5% (85.0% and 92.3% with or without bPI) in the MT group, without significant differences regarding the use of bPI. ETR was discontinued in 8.8% of patients for adverse events in 23.9% of cases (21.5% in VF, 29.5% in MT), treatment failure in 15.2% (16.2% in VF, 7.4% in MT) or simplification in 5.4% (4.6% in VF, 7.4% in MT). In the VF group, factors associated with virological response were a longer duration of HIV infection (OR = 2.7; p < 0.001) and baseline HIV RNA < 5 log10 copies/mL (OR = 2.1; p = 0.002). Conclusion This study shows that in ART-experienced patients ETR is well tolerated with a high efficacy when combined with other active drugs, even when the regimen does not include a bPI.

Changes in Lipid Profiles of HIV(+) Adults over Nine Months at a Harare HIV Clinic: A Longitudinal Study.

HIV infection, together with ART, is associated with changes in biochemical, metabolic parameters and lipid profiles. The aim of this study was to compare changes in lipid profiles among HIV positive outpatients over nine months. 171 patients were investigated, 79% were ART experienced, and 82% of ART experienced patients were on NVP/EFV first line at baseline, but some patients changed ART groups over follow-up and classification was based on intent to treat. More than 60% ART naïve and ART experienced patients had some form of dyslipidemia either at baseline or at follow-up, but mean lipid values for the two groups were within normal limits. At baseline and follow-up, mean levels of TC and HDL were slightly higher in the ART experienced group. Interestingly, there was higher increase in HDL over time in the ART negative group compared to the ART positive group. There was a decrease in TC/HDL ratio in both groups over time, suggesting a reduction in calculated risk of CHD over time. HIV positive patients frequently show various forms of dyslipidemia, but there are no changes in average atherogenic lipid levels and results suggest reduced risk of CHD, mainly due to increases in HDL, after nine months of observation time.