Cohort Of HIV-infected Patients Research Articles

High prevalence of Mycobacterium tuberculosis bacteraemia among a cohort of HIV-infected patients with severe sepsis in Lusaka, Zambia.

Tuberculosis is recognised as one of the leading causes of severe sepsis among HIV-infected patients. Most patients with Mycobacterium tuberculosis bacteraemia have advanced HIV disease with CD4 counts less than 100 cells/μl and its presentation is non-specific in most instances. This was a cross-sectional study which was done by analyzing data from 201 adult HIV-infected patients who met the inclusion criteria for severe sepsis. The prevalence of Mycobacterium tuberculosis bactraemia in the study population was 34.8%. Severe sepsis caused by other etiologies was observed in 33 (16.4%) of the participants. Concomitant infection of Mycobacterium tuberculosis bactraemia with other organisms is not uncommon in patients with severe sepsis. This cohort of HIV-infected patients had severe immunosuppression with a median CD4 count of 51 (20-136) cells/μl with moderate anaemia, mean haemoglobin 8.0 (3.0) g/dl, and were generally underweight with a mean mid upper arm circumference (MUAC) of 21.0 (3.4) cm. Mycobacterium tuberculosis bacteraemia is very common in HIV-infected patients with advanced HIV disease who present with severe sepsis. Mycobacterium tuberculosis bacteraemia co-infection with aerobic organisms is not uncommon. Factors that were independently associated with Mycobacterium tuberculosis bacteraemia in our study population were MUAC and sodium level.

Hepatitis B and C Co-Infection in HIV Patients from the TREAT Asia HIV Observational Database: Analysis of Risk Factors and Survival.

BackgroundWe assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region.MethodsPatients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.ResultsA total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.ConclusionIn this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.

Comparative Impact of Suppressive Antiretroviral Regimens on the CD4/CD8 T-Cell Ratio: A Cohort Study.

Although different factors have been implicated in the CD4/CD8 T-cell ratio recovery in HIV-infected patients who receive effective antiretroviral therapy (ART), limited information exists on the influence of the regimen composition.A longitudinal study carried out in a prospective, single-center cohort of HIV-infected patients. ART regimens including non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), or integrase strand transfer inhibitors (INSTI) from patients who achieved long-term (≥6-month duration) virological suppression (HIV-RNA < 400 copies/mL) from January 1998 to June 2014 were analyzed. The impact of ART composition on the changes of the CD4/CD8 T-cell ratio was modeled using a mixed linear approach with adjustment for possible confounders.A total of 1068 ART regimens from 570 patients were analyzed. Mean (SD) age of the patients was 42.15 (10.68) years and 276 (48.42%) had hepatitis C virus (HCV) coinfection. Five hundred fifty-eight (52.25%) regimens were PI-based, 439 (40.10%) NNRTI-based, and 71 (6.65%) INSTI-based; 487 (45.60%) were initial regimens, 476 (44.57%) simplification, and 105 (9.83%) salvage regimens. Median (IQR) number of regimens was 1 (1–2) per patient, of 29 (14–58) months duration, and 4 (3–7) CD4/CD8 measurements per regimen. The median baseline CD4/CD8 ratio was 0.42, 0.50, and 0.54, respectively, with the PI-, NNRTI-, and INSTI-based regimens (P = 0.0073). Overall median (IQR) increase of CD4/CD8 ratio was 0.0245 (−0.0352–0.0690) per year, and a CD4/CD8 ratio ≥1 was achieved in 19.35% of the cases with PI-based, 25.97% with NNRTI-based, and 22.54% with INSTI-based regimens (P = 0.1406). In the adjusted model, the mean CD4/CD8 T-cell ratio increase was higher with NNRTI-based regimens compared for PI-based (estimated coefficient for PI [95% CI], −0.0912 [−0.1604 to −0.0219], P = 0.009). Also, a higher CD4/CD8 baseline ratio was associated with higher CD4/CD8 increase in the adjusted model (P = 0.001); by contrast, higher age (P = 0.020) and simplification of ART regimen (P = 0.003) had a negative impact on the CD4/CD8 ratio.Antiretroviral regimen composition has a differential impact on the CD4/CD8 T-cell ratio; NNRTI-based regimens are associated with enhanced CD4/CD8 T-cell ratio recovery compared to PI-based antiretroviral regimens.

Preventing long-term tenofovir renal toxicity by pharmacokinetic assessment

Tenofovir is the active metabolite of tenofovir disoproxil fumarate (TDF), a commonly used antiretroviral agent in HIV treatment and in HIV preexposure prophylaxis. After a long-term exposure, TDF is associated with kidney impairment. In the D:A:D study cohort of HIV-infected patients (22 603 HIV-infected patients with baseline estimated glomerular filtration rate (eGFR) 90 ml/min per 1.73 m), tenofovir exposure was associated after adjustment with an increased relative risk (1.18 a year) of developing chronic kidney disease (CKD) defined by the occurrence of an eGFR below 70 ml/min per 1.73 m [1]. Recent studies also suggested that tenofovir use in preexposure prophylaxis might also be associated with a weak decline in eGFR, a mean decrease in eGFR after 60 months of treatment was 6 ml/min in the Bangkok Tenofovir study [2], and around 2 ml/min per 1.73 m during a median follow-up of 18 months in Partners Prep Study [3]. The decline in eGFR associated with tenofovir use is not always reversible after treatment cessation [4]. Tenofovir has a mitochondrial toxicity in tubular cells, leading to kidney tubular dysfunction (KTD) [5]. KTD affects 10.6–19% of the patients receiving tenofovir [6,7]. Tubular tenofovir toxicity is probably dose dependent. Indeed, an association between high-trough tenofovir plasma concentrations and KTD (defined by hypophosphatemia, hypouricemia, nondiabetic glucosuria, b-2 microglobulinuria, or a-1 microglobulinuria) was previously observed [6,7]. However, a decrease in eGFR may be observed without evidence for KTD. It is crucial to identify mechanisms and risk factors of tenofovir renal toxicity. Tenofovir penetrates in tubular cells by several tubular transporters. Polymorphisms in genes encoding for tubular transporters organic cationic transporter 1, multidrug resistant protein 2 (MRP-2) and 4 (MRP-4) were associated with increased tenofovir plasma concentrations and increased risk of KTD or of decrease in eGFR [8–11].

Undertreated HIV and drug-resistant tuberculosis at a referral hospital in Irkutsk, Siberia.

A referral hospital for tuberculosis (TB) in Irkutsk, the Russian Federation. To describe disease characteristics, treatment and hospital outcomes of TB-HIV (human immunodeficiency virus). Observational cohort of HIV-infected patients admitted for anti-tuberculosis treatment over 6 months. A total of 98 patients were enrolled with a median CD4 count of 147 cells/mm(3) and viral load of 205 943 copies/ml. Among patients with drug susceptibility testing (DST) results, 29 (64%) were multidrug-resistant (MDR), including 12 without previous anti-tuberculosis treatment. Nineteen patients were on antiretroviral therapy (ART) at admission, and 10 (13% ART-naïve) were started during hospitalization. Barriers to timely ART initiation included death, in-patient treatment interruption, and patient refusal. Of 96 evaluable patients, 21 (22%) died, 14 (15%) interrupted treatment, and 10 (10%) showed no microbiological or radiographic improvement. Patients with a cavitary chest X-ray (aOR 7.4, 95%CI 2.3-23.7, P = 0.001) or central nervous system disease (aOR 6.5, 95%CI 1.2-36.1, P = 0.03) were more likely to have one of these poor outcomes. High rates of MDR-TB, treatment interruption and death were found in an HIV-infected population hospitalized in Irkutsk. There are opportunities for integration of HIV and TB services to overcome barriers to timely ART initiation, increase the use of anti-tuberculosis regimens informed by second-line DST, and strengthen out-patient diagnosis and treatment networks.

Randomized trial of a multidisciplinary lifestyle intervention in HIV-infected patients with moderate-high cardiovascular risk

ObjectiveTo assess the impact of a multidisciplinary lifestyle intervention on cardiovascular risk and carotid intima-media thickness (c-IMT) in HIV-infected patients with Framingham scores (FS) > 10%. DesignRandomized pilot study; follow-up 36 months. MethodsVirologically suppressed adult HIV-1-infected patients with FS >10% were randomized 1:1 to the intervention group (multidisciplinary lifestyle intervention) or control group (routine care). At baseline and months 12, 24 and 36, lipid parameters were analyzed and carotid ultrasound was performed to determine c-IMT and presence of plaques. Biomarkers were measured at baseline and month 36. The primary endpoints were lipid and FS changes at 36 months. ResultsFifty-four patients were included, 27 in each arm. Median age was 50.5 years, all patients but one were men, and FS was 16.5%. Relative to controls, total and LDL cholesterol had significantly decreased in the intervention group at 24 months (p = 0.039, p = 0.011, respectively). However, no differences between groups were found at month 36 in lipid variables, neither in FS. Tobacco use decreased in the intervention group (p = 0.031). At baseline, 74.5% of patients had subclinical atherosclerosis, and at month 36, we observed a progression in c-IMT that was greater in the intervention group (p = 0.030). D-dimer increased (p = 0.027) and soluble intercellular adhesion molecule-1 decreased (p = 0.018) at 36 months. ConclusionsIn this cohort of HIV-infected patients with FS>10% and a high percentage of subclinical atherosclerosis, a multidisciplinary lifestyle intervention resulted in a slight improvement in some cardiovascular risk factors and the FS during the first 2 years, but did not prevent c-IMT progression.

Human immunodeficiency virus infection does not worsen prognosis of liver transplantation for hepatocellular carcinoma

The impact of human immunodeficiency virus (HIV) infection on patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) is uncertain. This study aimed to assess the outcome of a prospective Spanish nationwide cohort of HIV-infected patients undergoing LT for HCC (2002-2014). These patients were matched (age, gender, year of LT, center, and hepatitis C virus (HCV) or hepatitis B virus infection) with non-HIV-infected controls (1:3 ratio). Patients with incidental HCC were excluded. Seventy-four HIV-infected patients and 222 non-HIV-infected patients were included. All patients had cirrhosis, mostly due to HCV infection (92%). HIV-infected patients were younger (47 versus 51 years) and had undetectable HCV RNA at LT (19% versus 9%) more frequently than non-HIV-infected patients. No significant differences were detected between HIV-infected and non-HIV-infected recipients in the radiological characteristics of HCC at enlisting or in the histopathological findings for HCC in the explanted liver. Survival at 1, 3, and 5 years for HIV-infected versus non-HIV-infected patients was 88% versus 90%, 78% versus 78%, and 67% versus 73% (P = 0.779), respectively. HCV infection (hazard ratio = 7.90, 95% confidence interval 1.07-56.82) and maximum nodule diameter >3 cm in the explanted liver (hazard ratio = 1.72, 95% confidence interval 1.02-2.89) were independently associated with mortality in the whole series. HCC recurred in 12 HIV-infected patients (16%) and 32 non-HIV-infected patients (14%), with a probability of 4% versus 5% at 1 year, 18% versus 12% at 3 years, and 20% versus 19% at 5 years (P = 0.904). Microscopic vascular invasion (hazard ratio = 3.40, 95% confidence interval 1.34-8.64) was the only factor independently associated with HCC recurrence. HIV infection had no impact on recurrence of HCC or survival after LT. Our results support the indication of LT in HIV-infected patients with HCC.

Incidence and Predictors of Tuberculosis among HIV/AIDS Infected Patients: A Five-Year Retrospective Follow-Up Study

Background: Despite increased deliverance of antiretroviral therapy (ART), morbidity and mortality from TB are still predominant among HIV/AIDS infected patients in Ethiopia. Thus, current study aimed to determine magnitude and predictors of tuberculosis among cohort of HIV infected patients at Arba Minch General Hospital, Ethiopia, 2015. Methods: Hospital based retrospective follow-up study was conducted among study population which was HIV/AIDS infected individuals registered from September 2007 to 2013. The data were collected using structured data abstraction form and four ART trained nurses were used to abstract the data. The data were checked for completeness, cleaned and entered into Epi Info 7.0 and analyzed using SPSS version (IBM-21). Results were summarized by using table of frequency, graph, and measure of central tendency. Statistical significance was inferred at P-value ≤ 0.05. Adjusted odd ratio (AOR) with 95% confidence interval (CI) was used to determine predictors. Result: Four hundred ninety six patient’s charts were abstracted. Cumulative and incidence density of tuberculosis were 21.4% (95% CI: 21.3, 21.44) and 5.36 per 100 person year respectively. Cigarette smokers (AOR: 2.82, 95% CI (1.27 - 6.27)), household with family size of 3 - 4 (AOR: 2.26, 95% CI (1.14 - 4.50)), baseline WHO clinical stage III (AOR: 20.26, 95% CI (7.09 - 57.6)) and IV (AOR: 22.9, 95% CI (6.91 - 76.4)) and heamoglobin level of <10 (AOR: 2.56, 95% CI (1.22 - 5.33)) were important predictors (risk factors) of tuberculosis among HIV infected patients. Conclusion and recommendation: Relatively high incident tuberculosis cases were established among HIV infected patients and history of cigarette smoking; family size; hemoglobin level and base line WHO clinical stage were responsible for this incidence. Therefore; early initiation of HAARTas per current guideline should get stressed, and the finding that smoking was important predictors for TB in Ethiopia had obvious TB control implication which required high attention focused on fighting against cigarette smoking among HIV infected cohort.

Magnitude and correlates of moderate to severe anemia among adult HIV patients receiving first line HAART in Northwestern Tanzania: a cross sectional clinic based study.

IntroductionModerate to severe anemia is an important clinical problem in HIV patients on Highly Active Antiretroviral Therapy. The rate of progression and mortality in this sub group of patients is high compared to non anemic patients. In sub Saharan Africa with scale up of Anti retroviral therapy, the magnitude of this problem is not known especially in Tanzania. This study aimed at determining the magnitude and correlates of moderate to severe anemia in HIV patients receiving first line ART in northwestern Tanzania.MethodsThis was a cross sectional clinic based study, involving adult HIV patients on first line Highly Active Antiretroviral Therapy at Bugando Medical Centre Care and Treatment Center. The patients’ data were analyzed using STATA version 11 to determine the prevalence of moderate to severe anemia and risk factors that could predict occurrence of anemia.ResultsIn this study 346 patients on Highly Active Anti-Retroviral Therapy were enrolled, of whom 100(40.46%) had moderate to severe anemia. The odds of being anemic were strongly predicted by Zidovudine based regime, low baseline CD4 count (< 200 cells/μl) and HIV stage 3&4 at enrollment. Most of the anemic patients had mean corpuscular volume of >100fl.ConclusionThe prevalence of moderate to severe anemia is significantly high in this cohort of HIV-infected patients on first line Anti Retroviral Therapy and it is strongly predicted by Zidovudine based regime, low baseline CD4 and HIV stage 3 and 4. On clinical grounds this suggests that patients who are initiated on Zidovudine based regimen and those in advanced HIV at enrollment should have regular haemoglobin follow up to identify anemia at its earliest stage to improve the clinical outcome of these patients.

Anaemia and Iron Homeostasis in a Cohort of HIV-Infected Patients: A Cross-Sectional Study in Ghana.

Aim. We determined the prevalence of anaemia and evaluated markers of iron homeostasis in a cohort of HIV patients. Methods. A comparative cross-sectional study on 319 participants was carried out at the Tamale Teaching Hospital from July 2013 to December 2013, 219 patients on HAART (designated On-HAART) and 100 HAART-naive patients. Data gathered include sociodemography, clinical history, and selected laboratory assays. Results. Prevalence of anaemia was 23.8%. On-HAART participants had higher CD4/CD3 lymphocyte counts, Hb, HCT/PCV, MCV, MCH, iron, ferritin, and TSAT (P < 0.05). Hb, iron, ferritin, and TSAT decreased from grade 1 to grade 3 anaemia and CD4/CD3 lymphocyte count was lowest in grade 3 anaemia (P < 0.05). Iron (P = 0.0072) decreased with disease severity whilst transferrin (P = 0.0143) and TIBC (P = 0.0143) increased with disease severity. Seventy-six (23.8%) participants fulfilled the criteria for anaemia, 86 (26.9%) for iron deficiency, 41 (12.8%) for iron deficiency anaemia, and 17 (5.3%) for iron overload. The frequency of anaemia was higher amongst participants not on HAART (OR 2.6 for grade 1 anaemia; OR 3.0 for grade 3 anaemia). Conclusion. In this study population, HIV-associated anaemia is common and is related to HAART status and disease progression. HIV itself is the most important cause of anaemia and treatment of HIV should be a priority compared to iron supplementation.

Quantification of darunavir and etravirine in human peripheral blood mononuclear cells using high performance liquid chromatography tandem mass spectrometry (LC–MS/MS), clinical application in a cohort of 110 HIV-1 infected patients and evidence of a potential drug–drug interaction

ObjectivesTo describe the validation of a sensitive high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) method allowing the simultaneous quantification of darunavir (DRV) and etravirine (ETR) in peripheral blood mononuclear cells (PBMCs) and its application in a cohort of HIV-1 infected patients. MethodsBlood samples were obtained from 110 patients. PMBCs were isolated using density gradient centrifugation. Drug extraction from PBMCs was performed with a 60:40 methanol–water (MeOH–H2O) solution containing deuterated IS (DRV-d9 and ETR-d8). The chromatographic separation was performed on a RP18 XBridge™ column. ResultsThe geometric mean (GM) of cell associated concentration ([DRV]CC) and plasmatic concentration ([DRV]plasma) were 360.5ng/mL (CI95%:294.5–441.2) and 1733ng/mL (CI95%:1486–2021), respectively. A geometric mean intracellular (IC)/plasma ratio (GMR) of 0.21 (CI95%:0.18–0.24) was calculated. Adjusted for dose/body surface area and post-intake time, a statistically significant correlation was observed between [DRV]Plasma and the eGFR (p=0.002) and between [DRV]Plasma and the concomitant use of ETR (p=0.038). For the 10 patients receiving ETR in addition to DRV, the GM of [ETR]Plasma (available for 8 out of 10 patients) and [ETR]CC were 492.3ng/mL and 2951ng/mL respectively. The GMR of ETR was 7.6 (CI95%: 3.61–13.83). ConclusionsA handy and sensitive high performance LC–MS/MS method allowing the simultaneous quantification of DRV and ETR in PBMCs has been described and successfully applied in the largest cohort of DRV-treated patients reported to date. ETR accumulates more efficiently in PBMCs compared to DRV. We have also highlighted a possible impact of ETR on DRV plasma concentrations requiring further investigations.

Characteristics of the epidemic process and the leading risk factors for HIV infection in conditions of a large metropolis

The HIV epidemic has been going on for nearly thirty years, it is a heterogeneous, dynamic and highly resistant to countermeasures. The Leningrad Region and the city of St. Petersburg today are referred to the most affected regions of the Russian Federation, as nearly 1% of the population of this city has HIVpositive status. Despite the decline in the HIV infection incidence of the resident population of the Central District, the epidemiological situation for HIV infection remains to be tense, due to the increase in the cumulative number of HIV-infected and AIDS patients, the increase ofthe morbidity rate and mortality in co-infected patients with HIV/tuberculosis, activation of the output of the epidemic in vulnerable groups into the general population. At the same time, a cohort of HIV-infected patients with a high risk of late detection of tuberculosis continues to form

The Epidemiology and Risk Factors Associated With Herpes Simplex Virus [HSV]-2 Infections in a Large Well Characterized Cohort of HIV-Infected Patients, 2006-2014

The Epidemiology and Risk Factors Associated With Herpes Simplex Virus [HSV]-2 Infections in a Large Well Characterized Cohort of HIV-Infected Patients, 2006-2014

Predictors of dropout from care among HIV-infected patients initiating antiretroviral therapy at a public sector HIV treatment clinic in sub-Saharan Africa.

BackgroundIn sub-Saharan Africa (SSA), antiretroviral therapy (ART) can prolong life for HIV-infected patients. However, patients initiating ART, especially in routine treatment programs, commonly dropout from care either due to death or loss to follow-up.MethodsIn a cohort of HIV-infected patients initiating ART at a public sector clinic in Uganda, we assessed predictors of dropout from care (a composite outcome combining death and loss to follow-up). From a large set of socio-demographic, clinical, and laboratory variables routinely collected at ART initiation, we selected those predicting dropout at P <0.1 in unadjusted analyses for inclusion into a multivariable proportional hazards regression model. We then used a stepwise backward selection procedure to identify variables which independently predicted dropout at P <0.05.ResultsData from 5,057 patients were analyzed. The median age was 33 years (IQR 28 to 40) and 27.4 % had CD4+ T-cell counts <100 cells/μL at ART initiation. The median duration of follow-up was 24 months (IQR = 14 to 42, maximum follow-up = 64 months). Overall dropout was 26.9 % (established cumulative mortality = 2.3 %, loss to follow-up = 24.6 %), 5.6 % were transferred to other service providers, and 67.5 % were retained in care. A diagnosis of Kaposi’s sarcoma (hazard ratio (HR) = 3.3, 95 % CI 2.5 to 4.5); HIV-associated dementia (HR = 2.6, 95 % CI 1.5 to 4.6); history of cryptococcosis (HR = 2.2, 95 % CI 1.4 to 3.3); and reduced hemoglobin concentration (<11 g/dl versus ≥13.8 g/dl (HR = 1.9, 95 % CI 1.6 to 2.2) were strong predictors of dropout. Other independent predictors of dropout were: year of ART initiation; weight loss ≥10 %; reduced total lymphocyte count; chronic diarrhea; male sex; young age (≤28 years); and marital status.ConclusionsAmong HIV-infected patients initiating ART at a public sector clinic in SSA, biological factors that usually predict death were especially predictive of dropout. As most of the dropouts were lost to follow-up, this observation suggests that many losses to follow-up may have died. Future studies are needed to identify appropriate interventions that may improve both individual-level patient outcomes and outcome ascertainment among HIV-infected ART initiators in this setting.

Patterns of HIV viremia and viral suppression before diagnosis of non-AIDS-defining cancers in HIV-infected individuals.

BackgroundThe association between HIV viremia and non-AIDS-defining cancers (NADCs) is not well characterized. Viremia may contribute directly or indirectly to cancer development and may have a differential impact on various cancer types. Our objective was to characterize patterns of HIV viremia in a retrospective, urban, clinical cohort (N = 320) of patients diagnosed with NADCs.FindingsThe most common NADC’s were lung (n = 60), prostate (n = 47), oropharyngeal (n = 32), liver (n = 29), and anal cancer (n = 20) and Hodgkin lymphoma (n = 18). In the year before cancer diagnosis, 66 % of all patients were virally suppressed. Patients with oropharyngeal (70 %) and prostate cancer (78 %) had a higher proportion of visits with suppressed viral loads. Patients diagnosed with anal cancer and Hodgkin lymphoma were infrequently virally suppressed and more frequently had viral loads ≥5 log10 copies/ml in the ten years prior to cancer diagnosis.ConclusionsIn this cohort of HIV-infected patients diagnosed with NADCs, there were important differences in the patterns and levels of viremia between the different NADCs in the ten years prior to cancer diagnosis. Patients with anal cancer and Hodgkin lymphoma had the highest proportion of high level viremia in the ten years before cancer and the lowest frequency of viral load suppression at cancer diagnosis.

Impact of Illicit Drug Use on Health-Related Quality of Life in Opioid-Dependent Patients Undergoing HIV Treatment.

To assess the impact of illicit drug use on health-related quality of life (health utility) among opioid-dependent HIV-infected patients. Secondary analyses of data from the Buprenorphine-HIV Evaluation and Support cohort of HIV-infected patients with opioid dependence in 9 US HIV clinics between 2004 and 2009. Health status [short form-12 (SF-12)], combination antiretroviral treatment (ART) status, CD4 cell count, hepatitis C virus antibody status, current drug use, and demographics were assessed at the initial visit and quarterly follow-up visits until 1 year. The SF-6D health utility scores were derived from the SF-12. Multivariate mixed-effects regression models were used to assess the impact of illicit drug use on health utility controlling for demographic, clinical, and social characteristics. Health utility was assessed among 307 participants, 67% male, with a median age of 46 years at 1089 quarterly assessments. In multivariate analyses, illicit opioid use, nonopioid illicit drug use, not being on ART, and being on ART with poor adherence were associated with lower health utility. The observed decrement in health utility associated with illicit opioid use was larger for those on ART with good adherence (beta = -0.067; P < 0.01) or poor adherence (-0.049; P < 0.01) than for those not on ART. Illicit opioid and nonopioid drug use are negatively associated with health utility in patients with HIV; however, the relative effect of illicit opioid use is smaller than that of not being on ART. Postponing ART until initiation of opioid substitution therapy or abstinence may have limited benefits from the perspective of maximizing health utility.

Higher Activation in CD4+ T Cells But Similar Viral Control Among HIV/Hepatitis C Virus-Coinfected Patients on a Simplification Monotherapy

The aim of this study was to assess whether hepatitis C virus (HCV) coinfection would affect the clinical and immunological outcome of HIV-infected patients following a simplification strategy. A prospective cohort of HIV-infected patients starting a ritonavir boosted darunavir monotherapy (mtDRV/rtv) was followed for 24 months. HCV infection was evaluated by HCV viremia and hepatic fibrosis. Immune activation was studied as HLA-DR CD38 coexpression on CD4(+) and CD8(+) T cells and also the quantification of plasma sCD14 levels. Microbial translocation was studied by the plasma levels of 16S rDNA and lipopolysaccharide (LPS). A total of 150 HIV-infected patients were enrolled in this study, including 46 individuals also infected with HCV (30.6%). HIV/HCV coinfection did not decrease mtDRV/rtv efficacy, since similar rates of HIV-1 intermittent viremia (HCV: 26.6% vs. no-HCV: 34.7%) and episodes of virological failure (HCV: 22.2% vs. no-HCV: 11.2%, p-value = 0.381) were found. No major differences were found between both groups at baseline, although higher HLA-DR(+)CD38(+)CD4(+) T cell counts were found in the coinfected group (HCV: 6.65% vs. no-HCV: 4.55%, p-value = 0.032); this difference was maintained in the 24 months of follow-up. After the 24-month follow-up, both groups, HIV-monoinfected patients and HIV/HCV-coinfected patients, presented similar immune activation and microbial translocation profiles. In conclusion, the use of a simplified mtDRV/rtv strategy compromises neither HIV nor HCV viremic control in coinfected patients, although a higher immune activation of CD4(+) T cells was found.

CoVaMa: Co-Variation Mapper for disequilibrium analysis of mutant loci in viral populations using next-generation sequence data

Next-Generation Sequencing (NGS) has transformed our understanding of the dynamics and diversity of virus populations for human pathogens and model systems alike. Due to the sensitivity and depth of coverage in NGS, it is possible to measure the frequency of mutations that may be present even at vanishingly low frequencies within the viral population. Here, we describe a simple bioinformatic pipeline called CoVaMa (Co-Variation Mapper) scripted in Python that detects correlated patterns of mutations in a viral sample. Our algorithm takes NGS alignment data and populates large matrices of contingency tables that correspond to every possible pairwise interaction of nucleotides in the viral genome or amino acids in the chosen open reading frame. These tables are then analysed using classical linkage disequilibrium to detect and report evidence of epistasis. We test our analysis with simulated data and then apply the approach to find epistatically linked loci in Flock House Virus genomic RNA grown under controlled cell culture conditions. We also reanalyze NGS data from a large cohort of HIV infected patients and find correlated amino acid substitution events in the protease gene that have arisen in response to anti-viral therapy. This both confirms previous findings and suggests new pairs of interactions within HIV protease. The script is publically available at http://sourceforge.net/projects/covama.

Hepatitis C virus coinfection independently increases the risk of cardiovascular disease in HIV‐positive patients

Patients infected with HIV are at increased risk for cardiovascular disease despite successful antiretroviral therapy. Likewise, chronic hepatitis C virus (HCV) infection is associated with extrahepatic complications, including cardiovascular disease. However the risk of cardiovascular disease has not been formally examined in HIV/HCV-coinfected patients. A retrospective study was carried out to assess the influence of HCV coinfection on the risk of cardiovascular events in a large cohort of HIV-infected patients recruited since year 2004. A composite event of cardiovascular disease was used as an endpoint, including myocardial infarction, angina pectoris, stroke or death due to any of them. A total of 1136 patients (567 HIV-monoinfected, 70 HCV-monoinfected and 499 HIV/HCV-coinfected) were analysed. Mean age was 42.7 years, 79% were males, and 46% were former injection drug users. Over a mean follow-up of 79.4 ± 21 months, 3 patients died due to cardiovascular disease, whereas 29 suffered a first episode of coronary ischaemia or stroke. HIV/HCV-coinfected patients had a greater incidence of cardiovascular disease events and/or death than HIV-monoinfected individuals (4% vs 1.2%, P = 0.004) and HCV-monoinfected persons (4% vs 1.4%, P = 0.5). After adjusting for demographics, virological parameters and classical cardiovascular disease risk factors (smoking, hypertension, diabetes, high LDL cholesterol), both HIV/HCV coinfection (HR 2.91; CI 95%: 1.19-7.12; P = 0.02) and hypertension (HR 3.65; CI 95%: 1.34-9.94; P = 0.01) were independently associated with cardiovascular disease events and/or death in HIV-infected patients. Chronic hepatitis C and hypertension are independently associated with increased cardiovascular disease risk in HIV-infected patients. Therefore, treatment of chronic hepatitis C should be prioritized in HIV/HCV-coinfected patients regardless of any liver fibrosis staging.

Retention in Care of Adult HIV Patients Initiating Antiretroviral Therapy in Tigray, Ethiopia: A Prospective Observational Cohort Study.

IntroductionAlthough Ethiopia has been scaling up the antiretroviral therapy (ART) services, low retention in care of patients remains one of the main obstacles to treatment success. We report data on retention in care and its associated determinants in Tigray, Ethiopia.MethodsWe used data from the CASA project, a prospective observational and multi-site study of a cohort of HIV-infected patients who initiated ART for the first time in Tigray. Four participating health facilities (HFs) located in the South of Tigray were considered for this study. Patients were followed for one year after ART initiation. The main outcome measure was represented by the current retention in care, defined as the proportion of patients who were alive and receiving ART at the same HF one year after ART initiation. Patients who started ART between January 1, 2013 and December 31, 2013 were included in this analysis. Patients were followed for one year after ART initiation. The determinants of retention were analysed using univariate and multivariate Cox Proportional Hazards model with robust sandwich estimates to account for within HF correlation.ResultsThe four participating HFs in Tigray were able to retain overall 85.1% of their patients after one year from starting ART. Loss to follow-up (5.5%) and transfers to other HF (6.6) were the main determinant of attrition. A multivariate analysis shows that the factors significantly associated with retention were the type of HF, gender and active TB. Alamata health center was the HF with the highest attrition rate (HR 2.99, 95% CI: 2.77–3.23). Active TB (HR 1.72, 95% CI: 1.23–2.41) and gender (HR 1.64, 95% CI: 1.10–2.56) were also significantly associated with attrition.ConclusionsAlthough Ethiopia has significantly improved access to the ART program, achieving and maintaining a satisfactory long-term retention rate is a future goal. This is difficult because of different retention rates among HFs. Moreover specific interventions should be directed to people of different sex to improve retention in care in male population.