This trial assessed the rate of virological failure at 48 weeks in adult human immunodeficiency virus (HIV) type 1-infected patients assigned indinavir/ritonavir (Idv/Rtv; 800/100 mg 2 times daily) or saquinavir/ritonavir (Sqv/Rtv; 1000/100 mg 2 times daily) in an open-label, randomized (1:1), multicenter, phase 4 design. Three hundred six patients began the assigned treatment. At 48 weeks, virological failure was seen in 43 (27%) of 158 and 37 (25%) of 148 patients in the Idv/Rtv and Sqv/Rtv arms, respectively. The time to virological failure did not differ between study arms (P=.76). When switching from randomized treatment was counted as failure, this was seen in 78 of 158 patients in the Idv/Rtv arm, versus 51 of 148 patients in the Sqv/Rtv arm (P=.009). A switch from the randomized treatment occurred in 64 (41%) of 158 patients in the Idv/Rtv arm, versus 40 (27%) of 148 patients in the Sqv/Rtv arm (P=.013). Sixty-four percent of the switches occurred because of adverse events. A greater number of treatment-limiting adverse events were observed in the Idv/Rtv arm, relative to the Sqv/Rtv arm. In conclusion, Rtv-boosed Sqv and Idv were found to have comparable antiretroviral effects in the doses studied.

European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator conditions (IC). Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC), HIV test accepted (% of tests performed/% of tests offered) and new HIV diagnosis rate (%). There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32–97), lowest in Northern Europe (median 44%, IQR 22–68%) and highest in Eastern Europe (median 99%, IQR 86–100). Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0–4.9), with 29 audits (60.4%) having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14). A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested.

The risk of immunological failure in patients with an immunological response to HAART diminishes with a longer time receiving treatment and is associated with pretreatment CD4(+) cell count, ongoing viral replication, and intravenous drug use.

Although the absolute incidence is low, the current CD4(+) cell count and HIV-1 RNA level are strong predictors of most OIs in patients with high CD4(+) cell counts.

In the present study we compared the clinical presentations of patients with a clinical diagnosis of AIDS and disseminatedMycobacterium genavense infection (n = 12) with those of patients with AIDS and disseminated M. aviumcomplex (MAC) infection (n = 24). Abdominal pain was seen more frequently in the group of patients infected with M. genavense than in patients infected with MAC (P= 0.003). Analysis of microbiological data revealed that stool specimens from patients infected with M. genavense were more often smear positive than stool specimens from patients infected with MAC (P = 0.00002). However, M. genavense could be cultured on solid media from only 15.4% of the stool specimens, whereas MAC could be cultured from 71.4% of the specimens. Bone marrow and liver biopsy specimens yielded growth ofM. genavense within a reasonably short time, allowing species identification by DNA technology. Microbiological data clearly demonstrated the importance of acidic liquid medium for primary culture, the avoidance of pretreatment and the use of additives in culture, and the necessity for prolonged incubation if M. genavense is suspected. Susceptibility testing showed thatM. genavense is sensitive to rifamycins, fluoroquinolones, and macrolides, whereas it is resistant to isoniazid. Susceptibility to ethambutol and clofazimine could not be evaluated. The mean survival times of patients in the two groups were similar.

After the introduction of HAART, employment rates have increased profoundly among HIV-infected individuals, but have remained lower than in the background population. During the same period, DRRs decreased among HIV-infected individuals, but still remained higher than in the background population.

Background It is cost-effective to perform an HIV test in people with specific indicator conditions (IC) with an undiagnosed HIV prevalence of at least 0.1%. Our aim was to determine the HIV prevalence for 14 different conditions across 20 European countries. Methods Individuals aged 18–65 years presenting for care with one of 14 ICs between January 2012 and June 2014 were included and routinely offered an HIV test. Logistic regression assessed factors associated with testing HIV positive. Patients presenting with infectious mononucleosis-like syndrome (IMS) were recruited up until September 2015. Results Of 10,877 patients presenting with an IC and included in the analysis, 303 tested positive (2.8%; 95% CI 2.5–3.1%). People presenting with an IC in Southern and Eastern Europe were more likely to test HIV positive as were people presenting with IMS, lymphadenopathy and leukocytopenia/ thrombocytopenia. One third of people diagnosed with HIV after presenting with IMS reported a negative HIV test in the preceding 12 months. Of patients newly diagnosed with HIV where data was available, 92.6% were promptly linked to care; of these 10.4% were reported lost to follow up or dead 12 months after diagnosis. Conclusion The study showed that 10 conditions had HIV prevalences > 0.1%. These 10 ICs should be adopted into HIV testing and IC specialty guidelines. As IMS presentation can mimic acute HIV sero-conversion and has the highest positivity rate, this IC in particular affords opportunities for earlier diagnosis and public health benefit.

IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and MethodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.