Higher HIV Viral Load Research Articles

Higher HIV Viral Load is Associated With Lower Levels of Vitamin D in Treatment-naïve HIV Patients.

Higher HIV Viral Load is Associated With Lower Levels of Vitamin D in Treatment-naïve HIV Patients.

Elevated alanine aminotransferase levels in HIV-infected persons without hepatitis B or C virus coinfection

BACKGROUNDMortality related to human immunodeficiency (HIV) has improved with the use of antiretroviral therapy; however, liver disease–related mortality remains a major concern for the HIV population. Elevation of alanine aminotransferase (ALT) has been noted in HIV-infected persons even without viral hepatitis infection.OBJECTIVEThe objective of this study was to determine the incidence and prevalence of chronic alanine ALT elevation among patients infected with HIV who are negative for hepatitis B or C infection.DESIGNRetrospective chart review.SETTINGSWe reviewed the medical records of all patients infected with HIV who had been treated from November 2002 to December 2010.PATIENTS AND METHODSPatients with an unknown or positive HBV or HCV infection status were excluded. We identified patient demographics, route of transmission, peak viral load, and nadir CD4 count.RESULTSWe followed 440 patients for up to 2265 person-years. A total of 123 patients developed chronically elevated ALT levels, with an incidence of 5.8 cases per 100 person-years. Chronically elevated ALT levels were associated with high HIV viral load, mean body mass index, and diabetes mellitus. We found exposure to lamivudine in 58% of the patients, efavirenz in 41%, and zidovudine in 38%. Abdominal ultrasounds revealed fatty liver in 20 of 39 (51%) of the patients.CONCLUSIONAmong patients without viral hepatitis coinfection, the prevalence and incidence of chronic elevated ALT levels were high and accompanied by high HIV RNA levels and increased BMI.LIMITATIONSThe limitations of this report are its retrospective nature and lack of a control group.

Home testing and counselling to reduce HIV incidence in a generalised epidemic setting: a mathematical modelling analysis

SummaryBackgroundHome HIV testing and counseling (HTC) achieves high levels of HIV testing and linkage to care. Periodic home HTC, particularly targeted to those with high HIV viral load, may facilitate expanding antiretroviral therapy (ART) coverage. We used a mathematical model to assess the impact of periodic home HTC programs on HIV incidence in KwaZulu-Natal, South Africa.MethodsWe developed a dynamic HIV transmission model with parameters, primary cost data, and measures of viral suppression collected from a prospective study of home HTC in KwaZulu-Natal. We assumed five-yearly home HTC with ART initiation for persons with CD4≤350 cells/µL. For individuals with CD4>350 cells/µL, we compared increasing ART coverage for those who have CD4 counts 350–500 cells/µL with those who have viral loads >10,000 copies/mL.FindingsMaintaining the current level of 36% viral suppression among HIV-positive persons, HIV incidence decreases by 34% over 10 years. Five-yearly home HTC and linkage to care with ART initiation at CD4≤350 cells/µL reduces HIV incidence by 57% over 10 years. Expanding ART to persons with CD4>350 cells/µL who also have VL>10,000 copies/mL decreases HIV incidence by 68%, and was the most cost-effective strategy for preventing HIV infections at $2,960 per infection averted. Expanding ART eligibility to persons with CD4 350–500 cells/µL is cost-effective at $900 per QALY gained. Following health economic guidelines, expanding ART use to those who have VL>10,000 copies/mL among those with CD4>350 cells/µL was cost-effective to reduce HIV-related morbidity.InterpretationIn KwaZulu-Natal, five-yearly province-wide home HTC can cost-effectively increase ART coverage and reduce HIV burden. ART initiation criteria based on VL>10,000 copies/mL for those with CD4>350 cells/µL is also an efficient strategy for HIV prevention.

Timing of Antiretroviral Treatment, Immunovirologic Status, and TB Risk: Implications for Testing and Treatment.

Tuberculosis (TB) risk and mortality increase in the 6 months after highly active antiretroviral therapy (HAART) initiation. This short-term risk may be a consequence of HAART initiation and immune reconstitution. Alternatively, it may be due to confounding by low CD4 counts and high HIV viral loads (VLs). We assessed the TB risk before and after HAART initiation while appropriately controlling for time-updated laboratory values and HAART exposure. We conducted an observational cohort study among persons enrolled in the North American AIDS Cohort Collaboration on Research and Design from 1998 through 2011. A marginal structural model was constructed to estimate the association of HAART initiation and TB risk. Inverse probability weights for the probability of HAART initiation were incorporated. Among 26,342 patients, 94 cases of TB were diagnosed during 147,557 person-years (p-y) of follow-up. The unadjusted TB rates were 93/100,000 p-y [95% confidence interval (CI): 63 to 132] before HAART initiation, 203/100,000 p-y (95% CI: 126 to 311) ≤6 months after HAART initiation, and 40/100,000 p-y (95% CI: 29 to 55) >6 months on HAART. After controlling for time-updated laboratory values, the adjusted odds of TB ≤6 months after HAART initiation and >6 months was 0.65 (95% CI: 0.28 to 1.51) and 0.29 (95% CI: 0.16 to 0.53), respectively. TB risk in the first 6 months after HAART initiation is not higher than that before HAART initiation after adjusting for CD4 count and VLs. These findings suggest that short-term TB risk may be related to low CD4 counts and high VLs near HAART initiation and support early HAART initiation to decrease TB risk.

The Utility of a Syndemic Framework in Understanding Chronic Disease Management Among HIV-Infected and Type 2 Diabetic Men Who Have Sex with Men.

Syndemic theory posits that epidemics of multiple physical and psychosocial problems co-occur among disadvantaged groups due to adverse social conditions. Although sexual minority populations are often stigmatized and vulnerable to multiple health problems, the syndemic perspective has been underutilized in understanding chronic disease. To assess the potential utility of this perspective in understanding the management of co-occurring HIV and Type 2 diabetes, we used linear regression to examine glycemic control (A1c) among men who have sex with men (MSM) with both HIV and Type 2 diabetes (n=88). Bivariable linear regression explored potential syndemic correlates of inadequate glycemic control. Compared to those with adequate glycemic control (A1c≤7.5%), more men with inadequate glycemic control (A1c>7.5%) had hypertension (70 vs. 46%, p=0.034), high triglycerides (93 vs. 61%, p=0.002), depression (67 vs. 39%, p=0.018), current substance abuse (15 vs. 2%, p=0.014), and detectable levels of HIV (i.e., viral load ≥75 copies per ml blood; 30 vs. 10%, p=0.019). In multivariable regression controlling for age, the factors that were independently associated with higher A1c were high triglycerides, substance use, and detectable HIV viral load, suggesting that chronic disease management among MSM is complex and challenging for patients and providers. Findings also suggest that syndemic theory can be a clarifying lens for understanding chronic disease management among sexual minority stigmatized populations. Interventions targeting single conditions may be inadequate when multiple conditions co-occur; thus, research using a syndemic framework may be helpful in identifying intervention strategies that target multiple co-occurring conditions.

Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis.

Liver disease is a major cause of mortality among HIV-infected persons. There is limited information about the extent to which HIV disease severity impacts liver disease progression. We determined the incidence and predictors of advanced hepatic fibrosis measured by the Fibrosis-4 index (≥3.25) in a large diverse population of HIV-infected patients without significant liver disease at baseline (Fibrosis-4 score <1.45) in care between January 2000 and March 2014. We used Cox proportional hazards analysis to examine factors associated with progression to Fibrosis-4 score ≥3.25. Among 14,198 HIV-infected patients, hepatitis C virus (HCV) coinfection [adjusted hazard ratio (aHR) 1.9, 95% confidence interval (CI): 1.6 to 2.1], hepatitis B virus coinfection (aHR 1.5, 95% CI: 1.2 to 1.8), alcohol-use disorder (aHR 1.4, 95% CI: 1.2 to 1.6), and diabetes (aHR 1.9, 95% CI: 1.6 to 2.3) were associated with progression to advanced fibrosis in multivariable analysis. In addition, patients at each lower level of time-varying CD4 cell count had a significantly greater risk of progression, with ∼7-fold higher risk in those with CD4 <100 cells per cubic millimeter (aHR 6.9, 95% CI: 5.8 to 8.3) compared with CD4 ≥500 cells per cubic millimeter. An increasing gradient of risk was also observed among patients with higher time-varying HIV viral load (VL), with the greatest risk noted with VL ≥100,000 copies per milliliter (aHR 2.6, 95% CI: 2.2 to 3.1) compared with VL <500 copies per milliliter. Lower CD4 cell count and higher HIV VL were significantly associated with progression to advanced hepatic fibrosis in a dose-dependent manner, independent of the risk associated with traditional factors: hepatitis C virus or hepatitis B virus coinfection, alcohol, and diabetes. Our findings suggest that early treatment of HIV infection could mitigate liver disease.

Risk Factors Associated With Quantitative Evidence of Lung Emphysema and Fibrosis in an HIV-Infected Cohort.

The disease spectrum for HIV-infected individuals has shifted toward comorbid non-AIDS conditions including chronic lung disease, but quantitative image analysis of lung disease has not been performed. To quantify the prevalence of structural changes of the lung indicating emphysema or fibrosis on radiographic examination. A cross-sectional analysis of 510 HIV-infected participants in the multicenter Lung-HIV study was performed. Data collected included demographics, biological markers of HIV, pulmonary function testing, and chest computed tomographic examinations. Emphysema and fibrosis-like changes were quantified on computed tomographic images based on threshold approaches. In our cohort, 69% was on antiretroviral therapy, 13% had a current CD4 cell count less than 200 cells per microliter, 39% had an HIV viral load greater than 500 copies per milliliter, and 25% had at least a trace level of emphysema (defined as >2.5% of voxels <-950HU). Trace emphysema was significantly correlated with age, smoking, and pulmonary function. Neither current CD4 cell count nor HIV viral load was significantly correlated with emphysema. Fibrosis-like changes were detected in 29% of the participants and were significantly correlated with HIV viral load (Pearson correlation coefficient = 0.210; P < 0.05); current CD4 cell count was not associated with fibrosis. In multivariable analyses including age, race, and smoking status, HIV viral load remained significantly correlated with fibrosis-like changes (coefficient = 0.107; P = 0.03). A higher HIV viral load was significantly associated with fibrosis-like changes, possibly indicating early interstitial lung disease, but emphysematous changes were not related to current CD4 cell count or HIV viral load.

Factors associated with HIV RNA viral loads in ART-naïve patients: implications for treatment as prevention in concentrated epidemics

BackgroundLimited data are available on factors associated with HIV-RNA viral load (VL) among antiretroviral treatment (ART)-naïve key populations in concentrated epidemics. MethodsWe conducted a cross-sectional survey of 1211 adult ART-naïve patients at 19 HIV clinics in Ho Chi Minh City (HCMC), Vietnam. Data collection included a standardised questionnaire, routine laboratory testing, hepatitis serology and HIV VL. Correlation between CD4 cell count and VL was assessed across all participants. In 904 participants not meeting Vietnam criteria for ART (CD4 cell count >350 cells/mm3, WHO clinical stage 1 or 2 and not pregnant), multivariate analyses were conducted to assess factors associated with HIV VL. ResultsPre-ART patients had a median age of 31 years and 54% were male. Median CD4 cell count was 533 cells/mm3. Median HIV VL was 17,378 copies/mL; 60% had VL greater than 10,000 copies/mL and 16% had VL above 100,000 copies/mL. Although declining CD4 cell count was correlated with rising VL across all CD4 cell counts, correlation of VL with CD4 cell counts between 351 and 500 cell/mm3 was not significant. On multivariate linear regression, higher HIV VL was independently associated with male sex, men who have sex with men (MSM), CD4 cell count 351–500, HIV diagnosis within the previous 6 months, and hepatitis B (HBV). Lower HIV VL was independently associated with hepatitis C (HCV). ConclusionsThe majority of HIV patients who were not eligible for ART in HCMC in 2014 had HIV VL greater than 10,000 copies/mL. These data support expanded eligibility of ART to all HIV patients with the goal of treatment as prevention. This study is also among the first to demonstrate that MSM had a higher VL than women and heterosexual men and highlights the need for improved outreach and linkages to HIV care for this high-risk group.

Profile of HIV-Infected Hispanics with Pancytopenia

Pancytopenia is seen in late HIV infection; it is associated with medical complications and with decreased survival. We determined the prevalence of pancytopenia at baseline in a cohort of HIV-positive Hispanics living in Puerto Rico, and compared their socio-demographic, immunological and clinical characteristics. A total of 1202 patients enrolled between 2000 and 2010 were included. They were grouped according to pancytopenia status, defined by having: platelets <150,000 μL, white cell count <4000 μL, and hemoglobin <12 g/dL (women) or <13 g/dL (men). Differences were evaluated using Student’s t-test, Chi-square test and Kaplan-Meier method. The prevalence of pancytopenia was 8.7%. Patients with pancytopenia had lower BMI and lower CD4 count, as well as higher HIV viral load and higher proportions of unemployment, clinical AIDS and antiretroviral treatment (ART) use (p < 0.05). One-year mortality rate was significantly higher in patients with pancytopenia (18.1% vs. 5.1%, p < 0.001). When stratifying for ART this association persisted for patients who did not receive ART (41.4% vs. 5.2%, p < 0.001), but it was not seen in patients who received treatment (9.2% vs. 5.6%, p = 0.196). Pancytopenia was associated with elements of advanced stages of HIV. ART could reduce the mortality of HIV-patients with pancytopenia to levels comparable to patients without the disorders.

Antigenemia and real time polymerase chain reaction for diagnosis of cytomegalovirus disease in HIV infected adults

Cytomegalovirus (CMV) infection is frequent in HIV adults. It is unknown usefulness of quantitative methods for diagnosing the CMV disease in Chilean patients. To determine the performance of antigenemia and real time polymerase chain reaction (rtPCR) in the diagnosis of CMV disease in Chilean HIV adults. Detection of CMV by viral isolation (AVR), antigenemia and quantitative rtPCR in HIV adults. The 102 adults with suspected CMV disease had lower LTCD4 count and higher HIV viral load than 77 patients without suspicion (p < 0.05). Antigenemia and PCR were positive in 47 (46.1%) and 37 (36.3%) adults with clinical suspicion and in 2 (2.6%) and 4 (5.2%) of 77 without suspicion. The sensitivity, specificity, positive and negative predictive value of antigenemia and RPCtr were 92%, 80%, 72% and 95% and 72%, 95%, 92% and 80%, respectively. The cutoff values were ≥ lcell (+) and ≥ 5.5 log10 copies/2 x 10(6) cells. CMV was isolated in 6/179 patients (3.4%), all symptomatic. Positivity of antigenemia and rtPCR are similar for diagnosing CMV disease in Chilean HIV adults. AVR is inappropriate as a gold standard for its low performance.

P17.23 Implementing prioritised hiv linkage-to-care and contact tracing among individuals with high hiv viral load in baltimore, maryland, usa: results from a pilot program

Background Because of increased transmission potential, the US Centres for Disease Control and Prevention (CDC) recommends prioritising high HIV viral load (≥50,000 copies/mL, HVL) individuals for routine follow-up services, including linkage-to-care and partner services. However, little guidance exists on operationalizing this recommendation. In June 2014, the Baltimore City Health Department developed and implemented a pilot program to prioritise HVL individuals for follow-up services. The objective of this analysis is to describe the pilot program and evaluate process outcomes for follow-up services pre- and post-pilot program implementation. Methods This pilot program was modelled after a protocol for responding to congenital syphilis. Disease Intervention Specialists (DIS) were trained to locate, administer partner services interviews and link-to-care HVL individuals with increased urgency and effort compared to other HIV cases. A DIS supervisor reviewed each HVL case before closing to ensure adequate response and documentation. We used a pre-post design to evaluate the pilot and compared linkage-to-care and contact tracing outcomes for HVL individuals post pilot implementation (post-pilot, June 2014–January 2015) to a similar time period prior to implementation (pre-pilot, June 2013–January 2014). Results There were 23 pre-pilot and 17 post-pilot HVL cases (n = 40). DIS were more likely to link HVL individuals to care (59% pre-pilot vs. 65% post-pilot), and complete partner services interviews (39% pre-pilot vs. 59% post-pilot). Among HVL individuals who completed interviews, DIS were more likely to obtain sex partner meeting place information (33% pre-pilot vs. 40% post-pilot) and locating information for disclosed sex partners (16% pre-pilot vs. 39% post-pilot) in the post-pilot period compared to the pre-pilot period. Conclusion This pilot program demonstrates one successful method to operationalize CDC guidelines regarding prioritisation of HVL individuals. Future work will evaluate additional outcomes of this program, including HIV testing among sex partners and at sex partner meeting places disclosed by HVL individuals. Disclosure of interest statement The authors have no conflicts of interest to disclose.

Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa.

ObjectiveLimited data are available from the developing world on antiretroviral drug resistance in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in the context of a high tuberculosis burden. We describe the proportion of children with drug resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as associated factors.MethodsData from children initiated on protease inhibitor-based antiretroviral therapy with subsequent virological failure referred for genotypic drug resistance testing between 2008 and 2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined and associations with these mutations identified through logistic regression analysis.ResultsThe study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;-2.4]), high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47) and frequent tuberculosis co-infection (66%) at antiretroviral therapy initiation. Major protease inhibitor mutations were found in 49% of children and associated with low weight-for-age and height-for-age (p = 0.039; p = 0.05); longer duration of protease inhibitor regimens and virological failure (p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor (p = 0.038). On multivariate analysis, cumulative months on protease inhibitor regimens and use of ritonavir as single protease inhibitor remained significant (p = 0.008; p = 0.033).ConclusionMajor protease inhibitor resistance mutations were common in this study of HIV-1-infected children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing strategy proving to be important associated factors. There is an urgent need for safe, effective, and practicable HIV/tuberculosis co-treatment in young children and the optimal timing of treatment, optimal dosing of antiretroviral therapy, and alternative tuberculosis treatment strategies should be urgently addressed.

Recall of Nadir CD4 Cell Count and Most Recent HIV Viral Load Among HIV-Infected, Socially Marginalized Adults.

Lower nadir CD4 cell counts and higher HIV viral loads are associated with increased risks of adverse events in the progression of HIV disease. In cases where medical records are inaccessible or incomplete, little evidence is available regarding whether nadir CDR cell count or HIV viral load is reliably reported in any patient population. We compare survey data collected from 207 HIV-infected individuals detained in San Francisco jails to data collected from electronic medical records (EMR) kept by the jails and community health providers. The sensitivity of self-reported nadir CD4 cell count less than 200 was 82% [95% confidence interval (CI) 68, 88], and the sensitivity of reporting an undetectable most recent HIV viral load was 93% (95% CI 84, 97). This suggests that in a highly socially marginalized population, nadir CD4 cell count and most recent HIV viral load are recalled accurately when compared to EMR.

Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients.

The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir). Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23). Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P < 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir (P < 0.001) were associated with the presence of raltegravir-associated mutations at failure. Q148 mutations were selected more frequently in B subtypes versus non-B subtypes (P = 0.004). This study shows that a high proportion of viruses remain susceptible to dolutegravir in the case of failure on a raltegravir-containing regimen.

English

The estimated risk of contamination through percutaneous injuries involving HIV-contaminated sharp objects is 0.32%. It is well known that a high viral load is one of the conditions that increase the risk of HIV-1 transmission in occupational accidents. In order to estimate the level of viral load that could be necessary for HIV-1 transmission to health care workers undergoing occupational accidents with contaminated needles, blood-soiled needles were obtained from HIV-positive patients just after drawing blood to determine HIV-1 viral load by NASBA. Detection of HIV-1 genome was performed by reverse-transcription polymerase chain reaction (RT-PCR) after RNA extraction directly wash-outs collected from needles immediately after blood drawing. Samples collected from needles used on 102 HIV-1-positive patients were RT-PCR tested but only 7 were HIV-1-positive. Each patient sample was compared to its respective viral load. All 7 RT-PCR-positive samples were from patients with viral loads higher than 160,000 RNA copies/mm3. Since the needle samples tested here could be considered to be of very high risk of HIV-1 transmission following an occupational accident, RT-PCR detection of HIV-1 genome was only possible in patients with high viral load. These results indicate that, among all risk factors, high HIV-1 viral load probably is the most important risk factor for HIV transmission to health care workers during occupational exposure. Key words: HIV, viral load, polymerase chain reaction (PCR), RNA, occupational accidents.

Avascular osteonecrosis mechanism – between osteoporosis and antiphospholipid syndrome

HIV infected patients receiving antiretroviral therapy (ART) can develop avascular osteonecrosis, 45 times greater than the general population. Avascular osteonecrosis increased in the last few years in patients with HIV infection. The most important mechanisms for avascular osteonecrosis in HIV-infected patients are: changes in bone metabolism, especially osteoporosis correlated with protease inhibitors and coagulopathy and antiphospholipid syndrome, frequently described in HIV infection. Aim: to describe different mechanisms of avascular osteonecrosis We present two HIV-infected patients under antiretroviral therapy who developed avascular osteonecrosis. First patient, male, 38 year-old, with AIDS-C3, with good immuno-virological outcome under AZT-3TC and lopinavir/ritonavir, developed severe osteoporosis after 5 years of ART, diagnosed by DXA test with a T-score <-2,5. The patient had: C4-C5-C6 severe osteoporosis with high fracture risk, with segmental instrumentation applied at those levels, and then bilateral avascular necrosis of femoral head (ANFH) with bilateral hip arthroplasty. ART regimen was changed and the patient received 3TC-ABC and Nevirapine. The patient didn’t have other risk factors for avascular osteonecrosis or osteoporosis: nonsmoker, normal CD4, undetectable viral load, without dyslipidemia. Despite ART changes, the patient developed bilateral osteonecrosis of the right knee and of both humeral heads. The second patient, male, 23 year-old with HIV-B3, was treated in 2007 with AZT-3TC and lopinavir/ritonavir. After 9 months of ART the patient had normal CD4 count and undetectable viral load but developed right ANFH stage II, diagnosed by MRI, without surgery recommendation. DXA didn’t show signs of osteoporosis or osteopenia. The ART regimen was changed and the patient received 3TC-ABC and raltegravir with good ANFH outcome. After one year the patient discontinued the ART. One year later symptoms related with avascular osteonecrosis reappeared and bilateral ANFH was diagnosed by MRI. The patient had low CD4 count (<200/cmm), high HIV viral load and positive antiphospholipid antibodies. The patient had risk factors for coagulopathies: smoker, recreational drug user, alcohol consumer, uncontrolled HIV infection with low CD4. We restarted the same regimen with 3TC-ABC and raltegravir with a good outcome for bone affliction. When HIV infection was well-controlled, the antiphospholipid antibodies became negative and bone affliction was improved. We emphasize the importance of metabolic disturbances in HIV-infected patients, among them avascular osteonecrosis with different mechanisms. Both, ART and uncontrolled HIV infection can affect bone metabolism and vascularization.

HIV-associated Burkitt lymphoma with bone marrow and cerebral invasion in a patient with history of Plasmodium falciparum infection

HIV infected patients are more likely to develop non-Hodgkin lymphoma (NHL). Burkitt lymphoma (BL) is a highly aggressive NHL, associated with immunosuppression, especially with HIV. According to WHO classification there are three clinical types of BL: endemic, sporadic and immunosuppression-associated. Sporadic lymphoma was described especially in children (40% of child lymphomas in USA and EU). Two cofactors seem to be associated with BL: Ebstein Barr virus (EBV) and Plasmodium falciparum (PF) infection. PF and EBV are well-known co-factors in the pathogenesis of BL, but the mechanisms of interaction remain unclear. We present a 51 year-old male, who developed lymphadenopathy, prolonged fever, weight loss, splenomegaly and seizure. The patient was admitted to a Hematology University Hospital. After lymph node biopsy he was diagnosed with BL. A specimen of bone marrow from the right iliac crest showed gross invasion by Burkitt tumor cells. The patient tested positive for HIV and he was referred to the National Institute of Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest. According to CDC Classification System for HIV Infection the patient had AIDS (C3 stage with a CD4 count of 39/cmm) and a high HIV viral load (500,262 copies/mL). The patient’s medical history revealed Plasmodium falciparum malaria 4 years ago, while he was living in South America. Epidemiological data revealed more than 200 sexual partners in the last two years. At admission to our hospital he had pancytopenia: white blood cells 1400/cmm, with 600 neutrophils and 600 lymphocytes, hemoglobin 9.6 g/dL and platelet count 25,000/cmm. The patient was tested for EBV infection and high titer of anti-VCA antibodies was found. ART was initiated with TDF-FTC-lopinavir/r with good virological outcome (after 6 weeks of therapy the viral load was 383 copies/mL). Cerebral MRI showed diffuse lymphomatous invasion. After 3 weeks of ART the patient was referred to Hematology Hospital where chemotherapy was started. Post-chemotherapy the pancytopenia was more severe: white blood cells – 200/cmm with CD4 count – 10/cmm, platelets – 15,000/cmm and hemoglobin – 7.9 g/dL. The BL response after chemotherapy was poor and the patient died two months after the diagnosis, despite the good virological outcome. We present a rare case of NHL in a HIV-infected patient, with multiple co-factors for BL: HIV infection, EBV infection and Plasmodium falciparum infection. The prognostic in AIDS depends on the comorbidities’ outcome.

Hepatic HMOX1 expression positively correlates with Bach-1 and miR-122 in patients with HCV mono and HIV/HCV coinfection.

AimTo analyze the expression of HMOX1 and miR-122 in liver biopsy samples obtained from HCV mono-and HIV/HCV co-infected patients in relation to selected clinical parameters, histological examination and IL-28B polymorphism as well as to determine whether HMOX1 expression is dependent on Bach-1.Materials and MethodsThe study group consisted of 90 patients with CHC: 69 with HCV mono and 21 with HIV/HCV co-infection. RT-PCR was used in the analysis of HMOX1, Bach-1 and miR-122 expression in liver biopsy samples and in the assessment of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood. Moreover in liver biopsy samples an analysis of HO-1 and Bach-1 protein level by Western Blot was performed.ResultsHCV mono-infected patients, with lower grading score (G<2) and higher HCV viral load (>600000 IU/mL) demonstrated higher expression of HMOX1. In patients with HIV/HCV co-infection, the expression of HMOX1 was lower in patients with lower lymphocyte CD4 count and higher HIV viral load. IL28B polymorphism did not affect the expression of either HMOX1 or miR-122. Higher HMOX1 expression correlated with higher expression of Bach-1 (Spearman’s ρ = 0.586, p = 0.000001) and miR-122 (Spearman’s ρ = 0.270, p = 0.014059).ConclusionsHMOX1 and miR-122 play an important role in the pathogenesis of CHC in HCV mono-and HIV/HCV co-infected patients. Reduced expression of HMOX1 in patients with HIV/HCV co-infection may indicate a worse prognosis in this group. Our results do not support the importance of Bach-1 in repression of HMOX1 in patients with chronic hepatitis C.

Zinc deficiency facilitates disease progression in early HIV infected adults in Botswana (804.26)

Objective: Zinc deficiency facilitates HIV disease progression in late stages of the disease. We examined the association between plasma zinc levels with CD4 cell count and HIV viral load in asymptomatic, ART naïve HIV+ adults in Botswana.Methods: A secondary analysis from the Nutrient Therapy in Botswana for zinc deficiency (plasma zinc&lt;0.75mg/L) with CD4+ cell count, and log10 HIV viral load, used Mixed Model Linear Regressions from Baseline to 6‐months.Results: Among the 133 participants, mean age was 33.84, 52.21% were male and CD4 cell count was 463.69±162.05 cells/µL . The prevalence of zinc deficiency was 75.94%. Those with zinc deficiency had higher baseline viral load (4.19 vs. 3.64 log10 copies/mL). Over 6 months, participants with zinc deficiency had a lower CD4+ cell count [β=46.138, p=0.0503], and higher HIV viral load [β=‐0.2299, p=0.0518] controlling for age and gender.Conclusion: Zinc deficiency appears to have a detrimental effect on disease progression in HIV‐infected asymptomatic, ART naive adults. Further studies on the effect of normalizing zinc status and the mechanism through which adequate zinc contributes to slower disease progression are needed.Grant Funding Source: NIDA

Predictors of improvement following speed of processing training in middle-aged and older adults with HIV: a pilot study.

Speed of processing training has been shown to improve cognitive functioning in normal older adults. A recent study demonstrated that middle-aged and older adults with HIV also improved on a measure of speed of processing and a measure of everyday functioning after such training. The primary objective was to examine what predicts the speed of processing training gains observed in the previous study. Participants were administered an extensive battery of demographic, psychosocial, and neuropsychological measures at baseline. They were randomized either to the speed of processing training group (n = 22) or to a no-contact control group (n = 24). Participants received approximately 10 hours of computerized speed of processing training. Predictors of training gains on the Useful Field of View (UFOV) Test and the Timed Instrumental Activities of Daily Living (TIADL) Test were examined through correlational analyses. In general, those who performed worse on the UFOV and TIADL at baseline demonstrated significantly more training gains. Also, higher HIV viral load, poorer medication adherence, a higher number of years diagnosed with HIV, and lower baseline scores on the Wisconsin Card Sorting Test (an executive functioning measure) were correlated with better TIADL training gains. TIADL performance improved in those with higher HIV viral load, poorer medication adherence, and poor executive functioning. Speed of processing training may be a way to improve everyday functioning and therefore quality of life in more medically and cognitively vulnerable adults with HIV.