Physical and mental health in HIV-infected patients with virological success and long-term exposure to antiretroviral therapy.

In people living with HIV (PLWH), a decade-long antiretroviral therapy (ART) poses new challenges regarding physical and mental health. The aim of this cross-sectional study is to investigate the health-related quality of life (HRQOL) in adult HIV-infected patients with viral suppression and an ART exposure for at least 5 years in three German HIV centers. Patients were evaluated by the ACTG Augmented Symptoms Distress Module (ASDM) and the SF-12 Health Survey. Among 894 patients, symptom-related distress was highly prevalent. The most common symptoms were fatigue, insomnia, sadness and depression, sexual dysfunction, and changes in body appearance. In the multivariate analysis, ART duration, age and depression were significantly associated with a higher overall symptom summary score. Self-reported mean SF-12 scores were lower for mental health and younger patients compared to the standard random sample of a healthy German population. Depression and occupational status were significantly related to a lower physical component summary score, by contrast older age was associated with higher scores in the mental component summary, implying more favorable mental health status. In this large group of PLWH, the degree of symptom-related distress was high. Mental and physical health should be considered an integral part of ongoing HIV care.

Short-term neuropsychiatric tolerability of bictegravir combined with emtricitabine/tenofovir alafenamide in clinical practice.

BACKGROUND: Neuropsychiatric AEs (NPAEs) leading to dolutegravir (DTG) discontinuation were seen more frequently in real-world use than in randomized clinical trials (RCTs). The recently approved fixed-dose combination bictegravir plus emtricitabine and tenofovir alafenamide (BIC/F/TAF) has shown comparable NPAE rates but some favourable patient-reported outcomes in RCTs compared with DTG. We were interested in its neuropsychiatric tolerability in clinical practice. METHODS: All patients starting BIC/F/TAF from June 2018 in a single centre (two subcentres) were followed retrospectively. Discontinuation rates due to any AEs and NPAEs were compared with those of patients initiating DTG-based regimens. RESULTS: As of May 2019, a total of 943 patients (852 males, 76 females, 15 transgender and gender diverse) initiated BIC/F/TAF outside RCTs. After a median follow-up of 6.2 months, 50 (5.3%) and 31 (3.3%) patients had discontinued BIC/F/TAF due to any AEs or to NPAEs, respectively. In multivariate analysis, a pre-existing depression and subcentre remained predictive for NPAEs, but not age, gender, ethnicity or prior DTG-related AEs. Compared with 1,043 patients treated with DTG-based regimens, the estimated NPAE-related discontinuation rate with BIC/F/TAF was comparable during the first 6 months (P=0.36). Cross-intolerance was low, and only 5/55 patients with prior DTG intolerability had to discontinue BIC/F/TAF due to NPAEs. CONCLUSIONS: Short-term tolerability of BIC/F/TAF was comparable to DTG-containing regimens. As seen with DTG, discontinuation rates were higher than in RCTs. A pre-existing depression but also physician's awareness may have an impact on tolerability and continuation of BIC/F/TAF. In contrast, prior intolerability of DTG was of limited predictive value.

HIV-Associated Kaposi's Sarcoma.

Kaposi's sarcoma (KS) is still one of the most common malignancies in patients with human immunodeficiency virus (HIV) infection. Large randomized clinical trials have shown a protective effect of combination antiretroviral therapy (cART) against the development of KS, even in patients with a relatively preserved immune system. In patients with sufficient cART, KS has become a rarity. In most patients with HIV-associated KS who initiate cART, the KS lesions stabilize with decreasing HIV plasma viremia and immune reconstitution, or even resolve completely without any specific treatment. In patients with advanced or rapidly progressive disease, especially in the setting of an immune reconstitution syndrome, cART should be combined with cytotoxic chemotherapies. With regard to the KS pathogenesis, several new therapies have been suggested, such as antiviral agents, cytokines, and inhibitors of angiogenesis.

Everything fine so far? Physical and mental health in HIV-infected patients with virological success and long-term exposure to antiretroviral therapy.

INTRODUCTION: Little is known about the well-being on long-term exposure to antiretroviral therapy. The ACTG Augmented Symptoms Distress Module (ASDM) is a validated tool which measures the presence of a total of 22 symptoms seen with HIV and quantifies the extent to which they cause distress to the patient. METHODS: ELBE was a cross-sectional study that consecutively included adult HIV-infected patients presenting with viral suppression (<50 HIV RNA copies/mL) and ART exposure for at least five years. Patients were evaluated by four different questionnaires, including ASDM. RESULTS: Of a total of 894 patients included in the three participating ELBE centres, complete data on ASDM were available for 698 patients (626 male, 69 female, 3 transsexual). Median age was 49.7 years (range, 23.3-82.5 years) and median exposure to ART was 11.5 years (range, 5-28 years). Median CD4 T-cell counts had increased from a CD4 nadir of 180 to currently 640 cells/µL. Despite immunological and virological success, a high degree of symptom-related distress was noted in this patient population. In total, 63.8% and 36.3% of the patients had at least one "bothersome" or one "very bothersome" symptom, respectively. The symptoms most frequently reported to be "bothersome" or "very bothersome" were fatigue and energy loss (18.5% and 11.0% respectively), insomnia (12.8% and 11.6%), sadness and depression (13.0% and 10.0%), sexual dysfunction (12.0% and 10.0%), and changes in body appearance (11.0% and 10.9%). There was no association between the degree of symptom-related distress and gender, age or CD4 T-cell nadir. However, the history of AIDS-defining illnesses, comorbidities such as depression but also the duration of ART were significantly associated with a higher overall symptom summary score and with a higher frequency of symptoms. For example, in patients with at least 15 years of ART exposure, only 27.3% of the patients did not report at least one "bothersome" or "very bothersome" symptom. CONCLUSIONS: In this large group of positively selected HIV+ patients with virological success and long-term exposure to ART, a high degree of symptom-related distress was found. Medical care of HIV-infected patients should not only focus on optimal virological outcome. More data on quality of life in patients with long-term exposure to ART is needed.

Intermittent viraemia and immune reconstitution in patients with more than 10-15 years of antiretroviral therapy: baseline values still matter.

INTRODUCTION: Data on patients with long-term exposure to ART is scarce because controlled studies usually do not follow up patients for more than five to seven years. We were interested whether baseline parameters such as CD4 T-cell nadir or pre-treatment viraemia do have an impact on ART success after more than a decade of treatment. METHODS: ELBE is a cross-sectional study on adult HIV+ patients presenting consecutively with viral suppression (<50 HIV RNA copies/mL) and with ART exposure of at least five years. In this sub-analysis, all patients with more than 10 years of ART exposure were evaluated for immune reconstitution and for intermittent transient viraemia (50-1000 copies/mL, defined as "blips") during the last five years. RESULTS: From a total of 894 patients included in the three participating ELBE centres, 524 patients had an ART exposure of at least 10 years and had been treated continuously during the last 5 years. Of these, 33.4% had at least one "blip" while 63.5% did not show any transient viraemia of more than 50 copies/mL. Patients with at least one blip had a higher pre-treatment viraemia compared to patients without blips (5.30 versus 5.06 log copies/mL, p=0.0003). In patients with a pre-treatment viraemia of more than 100,000, 50,000-100,000 and less than 50,000 copies/mL, the proportions of patients with blips during the last five years were 39.5%, 30.5% and 21.8% (p=0.007), respectively. The history of an AIDS-defining illness or the CD4 T-cell nadir was not associated with a higher frequency of blips. However, CD4 T-cell nadir was a strong predictor for current CD4 T-cell counts. In patient groups with a CD4 T-cell nadir of 0-99, 100-199, 200-349, 350+ cells/µL, the median current CD4 T cells were 571, 667, 710 and 890 cells/µL, respectively. These differences remained significant when the analysis was restricted to patients with more than 15 years of ART exposure (n=268). CONCLUSIONS: In this large group of positively selected HIV+ patients with long-term exposure to ART of at least 10-15 years, high pre-treatment viraemia was still associated with a higher frequency of intermittent transient viraemia ("blip"). A low CD4 T-cell nadir remained associated with a lower CD4 cell recovery. The clinical implications of these findings remain to be evaluated.

Ongoing epidemic of lymphogranuloma venereum in HIV-positive men who have sex with men: how symptoms should guide treatment.

INTRODUCTION: Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by chlamydia trachomatis (CT) genotype L (L1, L2 and L3). Recent outbreaks of LGV in Europe and North America affected mainly men who have sex with men (MSM). Infections with CT serotypes D-K are mostly associated with mild symptoms or may be clinically silent. However, infections with L genotypes are more invasive and induce anogenital ulcer or inguinal lymphadenopathy. MATERIALS AND METHODS: Between 2003 and 2013, anal or genital CT infections were diagnosed in 471 symptomatic patients attending the Infectious Diseases Center Hamburg (ICH). CT DNA was detected by PCR. CT genotyping of positive samples was performed by sequence analyses of omp1 PCR products (samples between 2003 and 2010). Samples between 2012 and 2013 were analyzed by genotype L specific real-time PCR. RESULTS: In total, 221 LGV patients were identified (3 in 2003; 11 in 2004; 26 in 2005; 33 in 2006; 24 in 2007; 16 in 2008; 18 in 2009; 15 in 2010; 17 in 2011; 26 in 2012 and 32 in 2013). One hundred ninety-eight of 221 (89.6%) patients with LGV were HIV-infected; 10 of 221 (4.5%) were HIV-negative, and the HIV-status unknown in 13 (5.9%). The majority of LGV positive patients (204/221; 92%) had anorectal symptoms (bloody proctitis, rectal pain, purulent or mucous discharge, tenesmus, constipation), compared to 17/221 (8%) who presented with genital symptoms as urethritis, genital ulcer or inguinal lymphadenopathy. Of 283 CT-positive patients with anorectal symptoms, genotype L was detected in 205 (72%), while non-L genotypes (D-K) were found in 78 (28%). In contrast, genotype L was found in only 6% of patients with genital symptoms (11/177), whereas 94% (166/177) were infected with non-L genotypes only. CONCLUSIONS: The epidemic of LGV among predominantly HIV+ MSM is ongoing. LGV might be underdiagnosed, especially in patients with anorectal symptoms. Infections with CT serotypes D-K are more often associated with urogenital symptoms or asymptomatic infection, whereas LGV genotypes are found most frequently in patients with rectal/intestinal symptoms. Anorectal CT infections in MSM should be further characterized by genotyping for LGV, as for LGV three weeks of doxycycline treatment are recommended. CT genotypes D-K generally require shorter antibiotic treatment. If CT genotyping is not available, the duration of treatment should be prolonged to three weeks empirically for CT-positive patients with anorectal or intestinal symptoms.

HIV-associated lung cancer: survival in an unselected cohort.

BACKGROUND: Lung cancer is one of the most common non-AIDS-defining malignancies in HIV-infected patients. However, data on clinical outcome and prognostic factors are scarce. METHODS: This was a national German multicentre, retrospective cohort analysis of all cases of lung cancer seen in HIV-infected individuals from 2000 through 2010. Survival was analyzed with respect to the use of antiretroviral therapy (ART), specific lung cancer therapies, and other potential prognostic factors. RESULTS: A total of 72 patients (mean age 55.5 y, CD4 T-cells 383/µl) were evaluated in this analysis. At time of lung cancer diagnosis, 86% were on ART. Of these, 79% had undetectable HIV-1 RNA (< 50 copies/ml) for a mean duration of 4.0 y. All but 1 patient were current or former heavy smokers (mean 42 package y). The median estimated overall survival was 1.08 y, with a 2-y overall survival of 24%. The prognosis did not improve during the observation time. A limited lung cancer stage of I-IIIA was associated with better overall survival when compared with the advanced stages IIIb/IV (p = 0.0003). Other factors predictive of improved overall survival were better performance status, CD4 T-cells > 200/µl, and a non-intravenous drug use transmission risk for HIV. CONCLUSIONS: Currently, most cases of lung cancer occur in the setting of limited immune deficiency and a long-lasting viral suppression. As in HIV-negative cases, the clinical stage of lung cancer is highly predictive of survival, and long-term overall survival can only be achieved at the limited stages. The still high mortality underscores the importance of smoking cessation strategies in HIV-infected patients.

Treatment of AIDS-related lymphomas: rituximab is beneficial even in severely immunosuppressed patients.

OBJECTIVE: AIDS-related lymphomas (ARLs) significantly contribute to mortality in HIV-infected patients. Optimal chemotherapy treatment and the use of rituximab remain controversial. The aim of the present cohort study was to analyze the outcome of HIV-infected patients diagnosed with ARL, with regard to the use of rituximab, clinical characteristics and histopathological markers. METHODS AND DESIGN: This observational uncontrolled multicenter cohort study included 163 HIV-infected patients with ARL diagnosed between January 2005 and December 2008 in Germany. RESULTS: Patients with CD20-positive ARL had a significantly better overall survival (OS) and progression-free survival (PFS) than patients with CD20-negative ARL [hazard ratio 0.28, 95% confidence interval (CI) 0.15-0.53 and hazard ratio 0.29, 95% CI 0.16-0.53]. In CD20-positive cases, the use of rituximab was associated with better OS and PFS (n = 128, hazard ratio 0.48, 95% CI 0.25-0.93 and hazard ratio 0.47, 95% CI 0.26-0.86), even in patients with severe immune deficiency at ARL diagnosis (CD4 T-cell count<100 cells/µl, n = 33; OS: hazard ratio 0.25, 95% CI 0.07-0.90). In multivariate analysis, CD4 T-cell counts more than 100 cells/µl and the use of rituximab were associated with better OS and PFS. In total, there were 12 polychemotherapy-associated deaths, which were not related to specific therapy regimens or to the use of rituximab. CONCLUSION: In patients with CD20-positive ARL, CD4 T-cell count at ARL diagnosis and the use of rituximab had strong impact on survival. Rituximab was beneficial in ARL even in the setting of severe immune deficiency and was not associated with an increased risk of fatal infections.

Improved outcome with rituximab in patients with HIV-associated multicentric Castleman disease.

Although HIV-associated multicentric Castleman disease (HIV-MCD) is not classified as an AIDS-defining illness, mortality is high and progression to lymphoma occurs frequently. At present, there is no widely accepted recommendation for the treatment of HIV-MCD. In this retrospective (1998-2010), multicentric analysis of 52 histologically proven cases, outcome was analyzed with respect to the use of different MCD therapies and potential prognostic factors. After a mean follow-up of 2.26 years, 19 of 52 patients died. Median estimated overall survival (OS) was 6.2 years. Potential risk factors, such as older age, previous AIDS, or lower CD4 T cells had no impact on OS. Treatment was heterogeneous, consisting of cytostatic and/or antiviral agents, rituximab, or combinations of these modalities. There were marked differences in the outcome when patients were grouped according to MCD treatment. Patients receiving rituximab-based regimens had higher complete remission rates than patients receiving chemotherapy only. The mean estimated OS in patients receiving rituximab alone or in combination with cytostatic agents was not reached, compared with 5.1 years (P = .03). Clinical outcome and overall survival of HIV-MCD have markedly improved with rituximab-based therapies, considering rituximab-based therapies (with or without cytostatic agents) to be among the preferred first-line options in patients with HIV-MCD.