A Single Quantifiable Viral Load Is Predictive of Virological Failure in Human Immunodeficiency Virus (HIV)-Infected Patients on Combination Antiretroviral Therapy: The Austrian HIV Cohort Study.

Background. Viral loads (VLs) detectable at low levels are not uncommon in patients on combination antiretroviral therapy (cART). We investigated whether a single quantifiable VL predicted virological failure (VF). Methods. We analyzed patients receiving standard regimens with at least 1 VL measurement below the limit of quantification (BLQ) in their treatment history. The first VL measurement after 6 months of unmodified cART served as baseline VL for the subsequent analyses of the time to reach single VL levels of ≥200, ≥400, and ≥1000 copies/mL. Roche TaqMan 2.0 was used to quantify human immunodeficiency virus-1 ribonucleic acid. Factors associated with VF were determined by Cox proportional hazards models. Results. Of 1614 patients included in the study, 68, 44, and 34 experienced VF ≥200, ≥400, and ≥1000 copies/mL, respectively. In multivariable analyses, compared with patients who were BLQ, a detectable VL ≤ 50 and VL 51-199 copies/mL predicted VF ≥ 200 copies/mL (hazards ratio [HR] = 2.19, 95% confidence interval [CI] = 1.06-4.55 and HR = 4.21, 95% CI = 2.15-8.22, respectively). In those with VL 51-199 copies/mL, a trend for an increased risk of VF ≥400 and VF ≥1000 copies/mL could be found (HR = 2.13, 95% CI = 0.84-5.39 and HR = 2.52, 95% CI = 0.96-6.60, respectively). Conclusions. These findings support closer monitoring and adherence counseling for patients with a single measurement of quantifiable VL <200 copies/mL.

Factors Associated with Low-Level Viraemia and Virological Failure: Results from the Austrian HIV Cohort Study.

BACKGROUND: In human immunodeficiency virus treatment adequate virological suppression is warranted, nevertheless for some patients it remains a challenge. We investigated factors associated with low-level viraemia (LLV) and virological failure (VF) under combined antiretroviral therapy (cART). MATERIALS AND METHODS: We analysed patients receiving standard regimens between 1st July 2012 and 1st July 2013 with at least one viral load (VL) measurement below the quantification limit (BLQ) in their treatment history. After a minimum of 6 months of unmodified cART, the next single VL measurement within 6 months was analysed. VF was defined as HIV RNA levels ≥ 200 copies/mL and all other quantifiable measurements were classified as LLV. Factors associated with LLV and VF compared to BLQ were identified by logistic regression models. RESULTS: Of 2276 participants, 1972 (86.6%) were BLQ, 222 (9.8%) showed LLV and 82 (3.6%) had VF. A higher risk for LLV and VF was shown in patients with cART interruptions and in patients with boosted PI therapy. The risk for LLV and VF was lower in patients from centres using the Abbott compared to the Roche assay to measure VL. A higher risk for LLV but not for VF was found in patients with a higher VL before cART [for >99.999 copies/mL: aOR (95% CI): 4.19 (2.07-8.49); for 10.000-99.999 copies/mL: aOR (95% CI): 2.52 (1.23-5.19)] and shorter cART duration [for <9 months: aOR (95% CI): 2.59 (1.38-4.86)]. A higher risk for VF but not for LLV was found in younger patients [for <30 years: aOR (95% CI): 2.76 (1.03-7.35); for 30-50 years: aOR (95% CI): 2.70 (1.26-5.79)], people originating from high prevalence countries [aOR (95% CI): 2.20 (1.09-4.42)] and in male injecting drug users [aOR (95% CI): 2.72 (1.38-5.34)]. CONCLUSIONS: For both VF and LLV, factors associated with adherence play a prominent role. Furthermore, performance characteristics of the diagnostic assay used for VL quantification should also be taken into consideration.

Thyroid screening in HIV-infected patients with antiretroviral therapy.

BACKGROUND: The literature reports an increased incidence of thyroid disorders in human immunodeficiency virus (HIV)-positive persons. We therefore retrospectively analyzed the strategy of collecting thyroid parameters on a routine basis. METHODS: Overall 410 patients (147 women, 263 men; age, 10-74 years; median age, 45 years) were included. For screening purposes, three parameters were determined; basal thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3). Descriptive and statistical analyses were performed in the patient groups with increased bTSH (> 4.0 µU/ml) and with decreased fT4 (< 8.9 pg/ml) to evaluate possible correlation with age, gender, duration of antiretroviral therapy (ART), substance classes of ART (nucleosidal reverse transcriptase inhibitors (NRTIs), nonnucleosidal reverse transcriptase inhibitors, and protease inhibitors (PIs)), Centers for Disease Control and Prevention (CDC) disease stage, lowest number of CD4 cells during course of disease, and coexistent hepatitis C. RESULTS: Elevated bTSH was found in 27 patients (median, 5.26 µU/ml), who also showed a correlation with ART duration and NRTI use. Decreased fT4 was seen in 53 persons, and a correlation with PI intake was observed. Of these patients, 31 exhibited normalization in follow-up. Decreased fT3 was observed in eight cases related to nonthyroid illness, and fT3 was elevated in ten patients. No overt hyperthyroidism was noticed; three cases of subclinical hyperthyroidism were transient. CONCLUSIONS: In the examined group of patients, the prevalence of abnormal thyroidal parameters was 23 %. Decreased fT4, which does not require therapy, was observed most frequently (12 %) and correlated with PI use. On the other hand, elevated bTSH (6 %) correlated with ART duration and NRTI use. In mild subclinical hypothyroidism as observed in this patient population, thyroxine medication is not indicated in principle. Annual TSH screening is probably sufficient in HIV-infected patients with no clinical symptoms suggestive for thyroid disease.

Difference in factors associated with low-level viraemia and virological failure: results from the Austrian HIV Cohort Study.

INTRODUCTION: For some patients, it remains a challenge to achieve complete virological suppression which is the goal of antiretroviral therapy (ART). Identifying factors associated with low-level viraemia (LLV) and virological failure (VF) under ART might help to optimize management of these patients. MATERIALS AND METHODS: We investigated patients from the Austrian HIV Cohort Study receiving unmodified ART for >6 months with two nucleoside reverse-transcriptase inhibitors (NRTIs) with either a non-nucleoside reverse-transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) or an integrase inhibitor (INSTI) between 1 July 2012 and 1 July 2013 with at least one viral load (VL) measurement below the limit of detection (BLD) or below level of quantification (BLQ) in their treatment history. VF was defined as HIV-RNA levels ≥200 copies/mL and all other quantifiable measurements were classified as LLV. Factors associated with LLV and VF compared to BLD and BLQ were identified by using logistic regression models. RESULTS: Of the 2,276 patients analyzed, 1,972 (86.6%) were BLD or BLQ, 222 (9.8%) showed LLV and 82 (3.6%) had VF. A higher risk for LLV and VF was found in patients with ART interruptions and in patients with boosted PI therapy. The risk for LLV and VF was lower in patients from a centre which uses Abbott RealTime HIV-1 assay compared to the other centres measuring VL by the Roche Cobas AmpliPrep/Cobas TaqMan 2.0. A higher risk for LLV but not for VF was found in patients with a higher VL before ART and shorter ART duration. A higher risk for VF but not for LLV was found in patients of younger age, originating from a high prevalence country, with a lower CD4 count and in male injecting drug users. CONCLUSIONS: This study of well-defined patients on stable ART over a period of more than six months gives insights into the different factors associated with LLV and VF. In patients with VF, factors associated with adherence play a prominent role, whereas in patients with LLV, the biology of viral replication comes additionally into effect. Despite its observational design, it has implications for patient management and forms the basis for future outcome studies.

Treatment modification in HIV-Infected individuals starting antiretroviral therapy between 2011 and 2014.

INTRODUCTION: While antiretroviral therapy (ART) has increased the survival of HIV patients and turned HIV infection into a chronic condition, treatment modifications and poor adherence might limit this therapeutic success. METHODS: Patients from the Austrian HIV Cohort Study, who started their first ART after Rilpivirine became available in February 2011, were analyzed for factors associated with treatment modification which could be either a change of drugs or a stop of the regimen. A drug was considered as stopped when the regimen was interrupted for more than eight days. Drugs of particular interest were Darunavir (DRV), Atazanavir (ATV), Raltegravir (RAL), Rilpivirine (RPV) and Efavirenz (EFV). RPV and EFV were analyzed only when taken as single tablet regimen. Other drugs were summarized as "other." Proportional hazards regression methods were used to identify predictors of discontinuation and Kaplan-Meier estimates were used to calculate probabilities of discontinuation. Patients who died were censored at the date of death. RESULTS: 965 patients started ART, 282 with DRV, 161 with ATV, 96 with RAL, 108 with RPV and 118 with EFV. Median time for taking initial ART is 11.6 months. 322 (33.4%) patients modified their initial ART. The overall probability of modification at one year was 28.7%, at two years 40.0% and at three years 49.8%. In a multivariable proportional hazards regression analysis, AIDS diagnosis at baseline and injecting drug use (IDU) of men compared with men who have sex with men (MSM) have a higher risk of switch/stop. Compared with DRV, RPV showed a much lower and ATV and particularly "other" a higher risk for discontinuation (Table 1). CONCLUSION: Rates of modification and interruption were still high in recent years, particularly in the first year of ART. The decreased rate of modification found in patients treated with Rilpivirine may be attributed to selection of patients according to guidelines.

Preexposure prophylaxis and timed intercourse for HIV-discordant couples willing to conceive a child.

Many HIV-discordant couples express a strong wish to conceive a child. Insemination with processed semen is offered to these couples in many countries. Given the very low level of transmission risk during fully suppressive antiretroviral therapy, we offered timed intercourse combined with preexposure prophylaxis to further reduce the transmission risk. In 53 cases, natural conception was attempted using the proposed method. Pregnancy rates were high and reached a plateau of 75% after six cycles. Advanced age in the female partner was a predictor for infertility in these couples.

Genotypic prediction of human immunodeficiency virus type 1 tropism by use of plasma and peripheral blood mononuclear cells in the routine clinical laboratory.

We developed a sequencing assay for genotypic HIV-1 tropism determination. The assay allows examination of HIV RNA from plasma and HIV DNA from peripheral blood mononuclear cells (PBMC), including PBMC samples from patients with undetectable viral loads. Assessment of 100 pairs of plasma and PBMC samples showed a high concordance of 90%. With the limitations of population-based sequencing, the assay was found to be robust and suitable for the routine clinical laboratory.

Genotypic antiretroviral resistance testing for human immunodeficiency virus type 1 integrase inhibitors by use of the TruGene sequencing system.

A sequencing assay for detection of mutations conferring resistance to human immunodeficiency virus type 1 (HIV-1) integrase inhibitors raltegravir and elvitegravir was developed using the automated TruGene sequencing system. The assay returned clear sequencing results for samples with >or=500 RNA copies/ml for mutation detection and HIV-1 subtyping across a spectrum of HIV-1 subtypes.

Cytomegalovirus genotypes present in cerebrospinal fluid of HIV-infected patients.

OBJECTIVE: To compare cytomegalovirus (CMV) strains found in cerebrospinal fluid (CSF) of patients with HIV infection and CMV encephalitis with those present in the general population with respect to genetic variation in the N terminus of the glycoprotein B (gBn)-gene. DESIGN AND METHODS: We sequenced gBn, which is a major target of the antiviral immune response, of CMV strains present in CSF of nine HIV-infected patients with acute encephalitis, in serum of 18 immunocompetent patients with primary CMV infection, and in serum of nine HIV-infected patients without neurological illness. Sequences were compared to prototype strains and analysed by use of phylogeny. RESULTS: Fourty-four percent (4/9) of gBn-sequences present in CSF did not cluster with any of the four gBn-prototype strains. Phylogenetic analysis revealed that these sequences represented two further, distinct genotypes and comparison of sequences was highly suggestive for intragenic recombination. In immunocompetent patients and HIV-infected patients without neurological illness, genotype gBn1 was the predominant strain (4/9, 44% and 8/18, 42%, respectively). Genotypes distinct from prototype strains were found in none of the immunocompetent patients and 22% (2/9) of HIV- infected patients without neurological illness. CONCLUSIONS: CMV strains present in CSF of HIV-infected patients with encephalitis differ significantly from those present in the general population. Intragenic recombination of CMV may be common in patients with advanced HIV infection and a source of new CMV strains with altered biological properties.

Low proportion of recent human immunodeficiency virus (HIV) infections among newly diagnosed cases of HIV infection as shown by the presence of HIV-specific antibodies of low avidity.

The time between human immunodeficiency virus (HIV) infection and diagnosis is mostly unknown. Two hundred five newly diagnosed patients were investigated for the duration of their HIV infection by avidity testing. Recent HIV infection was identified in 27.3% of the cases. Early diagnosis was achieved significantly less frequently in heterosexually infected persons than in other patients.