Undetectable HIV Viral Load Research Articles

HIV/Hepatitis B Coinfection Is Usually Treated Together. Is Hepatitis B Forgotten?

BackgroundHepatitis B (HBV) co-infection increases the risk for liver-related morbidity among HIV-infected patients. Department of Health and Human Services (DHHS) guidelines for the management of HIV/HBV co-infection recommend six-monthly monitoring of blood tests. We assessed longitudinal adherence to these guidelines among patients enrolled in the DC Cohort Study, a city-wide clinical cohort in Washington, DC.MethodsPatients ≥18 years old who were enrolled between January 1, 2011 and March 31, 2016 and had ≥6 months of follow-up were included. Advanced liver fibrosis was defined as having a FIB-4 score >3.25 calculated from same-day platelet, AST and ALT results. Viral suppression (VS) was defined as having undetectable HIV VL (<200 copies/mL). Chronic HBV status was determined using ICD 9 and 10 diagnosis codes. Clinical targets were defined as the proportion tested for HBV viral load (VL), platelet count and AST (markers of HBV care) along with HIV VL and CD4 count tests (markers of HIV care) every six months following enrollment.ResultsAmong 7,631 HIV-infected patients, 354 (4.6%) had chronic HBV among whom 22 (6.2%) had advanced fibrosis. Compared with HIV-mono-infected patients, HIV/HBV patients were more likely to be male (86% vs 72%, P < 0.001) and had a history of AIDS (49% vs 37%, P < 0.001). Although HIV VS was high in both groups, co-infected patients were less likely to have undetectable HIV VL (88% in HIV only vs 84% in HIV/HBV, P = 0.026). HIV/HBV patients were nearly four times less likely to be tested for HBV than for HIV VL in the first six months (21% vs 79%, P <0.0001) and eight times less likely in the last six months of observation (6% vs 49%, P <0.0001). Comparing the first six months to the last six months of observation, the proportion of patients tested for AST (77% and 50% P < 0.0001) and platelets (76% and 57% P < 0.0001) declined.ConclusionAdherence to the DHHS management guidelines for monitoring HBV VL among HIV/HBV co-infected patients was low. AST and platelet counts were monitored at a similar frequency to HIV VL, suggesting that these markers may have been checked as part of routine HIV care than for HBV monitoring. Focusing on adherence to guidelines may ensure early detection of complications and provide patients with timely and appropriate care.Disclosures All authors: No reported disclosures.

Real World Experience of Sofosbuvir/Ledipasvir Therapy in HIV Patients Co-infected with HCV: A Retrospective Study

BackgroundDirect acting antiretrovirals in clinical trials have high efficacy achieving sustained virologic response (SVR) in Hepatitis C virus (HCV) and human-immunodeficiency virus (HIV) co-infected patients. We aim to investigate real-world HCV SVR outcome of ledipasvir/sofosbuvir therapy in the HIV population.MethodsWe performed a retrospective chart review from 2014 to 2016 of patients with HCV/HIV coinfection who received ledipasvir/sofosbuvir in a freestanding HIV clinic. Demographic data collected includes: HCV genotype (Gt), Fib-4 score, length of therapy (LOT), HIV viral load (VL), CD4+ cell count, antiretroviral therapy (ART), HCV RNA levels at baseline, 4 weeks, 8 weeks, end of therapy (EOT), and SVR at week 12 post-treatment. Statistical analysis was performed using Stata version 14 (STATA Corp., Texas, USA).ResultsA total of 94 patients were included. The mean age was 54 years-old, 78% were male. Most patients (95%) had Gt 1 HCV infection (84% 1A, 11% 1B and 1% mixed), 4% Gt 4, and one patient had Gt 6; 24% of patients had compensated cirrhosis.Median LOT was 12 weeks. 95% of patients received 12 weeks, 4% 24 weeks, and 1% received 16 weeks of therapy. Most patients had undetectable HIV VL (77% with <20 copies/mL), while 23% had HIV VL range from 20 to 1,430 copies/mL. The mean CD4+ count was 639 cells/microliters (95% CI 567–711). The most commonly used ARTs were efavirenz/emtricitabine/tenofovir (21%), followed by abacavir/dolutegravir/lamivudine (15%). SVR12 was achieved in 99% (93/94) of patients (100% in HCV treatment experienced). Of those patients, 86/91 achieved HCV VL <15 at week 4 and 80/82 at EOT. The mean Fib-4 score at start of therapy was 2.33 with post-therapy of 1.35. One patient (Gt 1A, F4, on FTC/TDF/RAL) failed therapy secondary to NS5a mutation (L31M/V) and was retreated with sofosubuvir/simeprevir for 12 weeks achieving SVR 12. Interestingly, 4 patients had undetectable HCV VL at EOT with post-EOT HCV viremia (157–4511 IU/mL) that resolved on its own on repeated testing.ConclusionOur HCV real-life experience with ledipasvir/sofosbuvir at a freestanding HIV clinic confirms the efficacy and safety reported in randomized clinical trials. NS5A mutation led to treatment failure in this heterogeneous group of patients.Disclosures All authors: No reported disclosures.

Discoid Lupus and Human Immunodeficiency Virus: A Retrospective Chart Review to Determine the Prevalence and Progression of Co-occurrence of these Conditions at a Single Academic Center.

Context:Discoid lupus erythematosus (DLE) and human immunodeficiency virus (HIV) are both disorders of the immune system. The pathophysiology of these diseases varies greatly as DLE is characterized by an overactive immune system that attacks normal host cells, whereas HIV is characterized by an exogenous attack on the immune system that depletes it of key cell types. Although the reason is unknown, co-occurrence of DLE and HIV is rare.Aims:The goal of this study is to determine the prevalence of co-occurrence of DLE and HIV and to determine whether patients with both DLE and HIV share any clinical feature.Subjects and Methods:The medical records of all patients seen within a single academic health center over a 20-year period were reviewed to determine the prevalence of cutaneous lupus, HIV, and co-occurrence of these conditions. The charts of patients diagnosed with both conditions were further reviewed to determine similarities between them.Results:Of the 10,719 patients diagnosed with HIV and 182 patients diagnosed with cutaneous lupus, only 2 patients were diagnosed with both conditions. Both of these patients were diagnosed with DLE several years after being diagnosed with HIV. They had an undetectable HIV viral load, normal CD4 T-cell counts, and were on antiretroviral therapy when diagnosed with DLE.Conclusion:These results confirm that co-occurrence of DLE and HIV is rare. Although our study population was small, findings from these patients suggest that in HIV-positive patients, DLE manifestations occur when their HIV disease activity is minimal.

CD4+ T cells and natural killer cells: Biomarkers for hepatic fibrosis in human immunodeficiency virus/hepatitis C virus-coinfected patients.

AIMTo characterize peripheral blood natural killer (NK) cells phenotypes by flow cytometry as potential biomarker of liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients.METHODSPeripheral mononuclear cells from 24 HIV/HCV (HBV negative) coinfected and 5 HIV/HCV/HBV seronegative individuals were evaluated. HIV/HCV coinfected patients were divided in to groups: G1, patients with METAVIR F0-F2 and G2, patients with METAVIR F3-F4. NK surface cell staining was performed with: Anti-CD3(APC/Cy7), anti-CD56(PE/Cy5), anti-CD57(APC), anti-CD25(PE), anti-CD69(FITC), anti-NKp30(PE), anti-NKp46(PE/Cy7), anti-NKG2D(APC), anti-DNAM(FITC); anti-CD62L (PE/Cy7), anti-CCR7(PE), anti-TRAIL(PE), anti-FasL(PE), anti CD94(FITC). Flow cytometry data acquisition was performed on BD FACSCanto, analyzed using FlowJo software. Frequency of fluorescence was analyzed for all single markers. Clinical records were reviewed, and epidemiological and clinical data were obtained.RESULTSSamples from 11 patients were included in G1 and from 13 in G2. All patients were on ARV, with undetectable HIV viral load. Liver fibrosis was evaluated by transient elastography in 90% of the patients and with biopsy in 10% of the patients. Mean HCV viral load was (6.18 ± 0.7 log10). Even though, no major significant differences were observed between G1 and G2 regarding NK surface markers, it was found that patients with higher liver fibrosis presented statistically lower percentage of NK cells than individual with low to mild fibrosis and healthy controls (G2: 5.4% ± 2.3%, G1: 12.6% ± 8.2%, P = 0.002 and healthy controls 12.2% ± 2.7%, P = 0.008). It was also found that individuals with higher liver fibrosis presented lower CD4 LT count than those from G1 (G2: 521 ± 312 cells/μL, G1: 770 ± 205 cells/μL; P = 0.035).CONCLUSIONHigher levels of liver fibrosis were associated with lower percentage of NK cells and LTCD4+ count; and they may serve as noninvasive biomarkers of liver damage.

Missed Opportunities for Primary Prevention of Cardiovascular Disease in an HIV Clinic

Background Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death among people living with HIV (PLWH). PLWH have a high prevalence of ASCVD risk factors, including hypertension (HTN), dyslipidemia, diabetes mellitus (DM), elevated BMI, smoking, physical inactivity, and poor diet.Methods Setting—Urban Ryan White funded clinic in Columbia, SC providing care to about 2200 PLWH. A retrospective chart review was performed on a sample of patients ≥40 years old. Patients were eligible if they did not have a known diagnosis of ASCVD, had ≥ 3 visits in the last 3 years, and at least 1 visit in the past 12 months. Data regarding demographics, comorbidities, lab values, medications, and recent blood pressures were abstracted. Data were collected on assessment and intervention for smoking, weight loss, diet, and exercise. Objectives of this study were to: (1) determine the prevalence of ASCVD risk factors among patients without known ASCVD; (2) estimate the proportion of patients who received appropriate pharmacologic and lifestyle interventions. ResultsCharts were reviewed in random order until 100 charts had the required variables to calculate the 10-year ASCVD risk (Figure 1). These complete charts were similar in demographic characteristics to the clinic population. Of the complete charts, 66% met BMI criteria for being obese or overweight; but < 30% of these patients had documentation of the diagnosis, or received appropriate intervention for diet, exercise, or weight loss. HTN was diagnosed in 42% of patients, and 52% of these were adequately controlled. An additional 9% met criteria for HTN but did not carry the diagnosis. Documented diagnosis of DM was surprisingly low at <5%. Nurses assessed smoking in 100% of patients, and the majority of smokers received an intervention. Based on current guidelines, less than 25% of eligible patients were prescribed a statin (Figure 2). To our concern, none of the patients with LDL ≥190 mg/dL or DM had evidence of statin therapy.Conclusion Although > 85% of clinic patients have an undetectable HIV viral load, there were multiple missed opportunities for primary prevention of cardiovascular disease, including interventions for smoking cessation, diet and exercise, and guideline based anti-HTN and statin therapy.Figure 1:Disclosures A. Jones, Proctor & Gamble: Stock, Dividend. CVS Health Corp: Stock, Dividend. Johnson & Johnson: Stock, Dividend. Baxter Inc.: Stock, Dividend. Becton-Dickinson: Stock, Dividend. United Health Group: Stock, Dividend

Leflunomide in the Treatment of a Pseudotumoral Genital Herpes Simplex Virus Infection in an HIV Patient

The patient is a 52-year-old African American man with a past medical history of HIV infection (on antiretroviral therapy, CD4 count 399 cells/µL, and undetectable HIV viral load) and recurrent genital herpes. While on valacyclovir, the patient presented with four tumorous lesions on the perineum and scrotum. A biopsy specimen stained positively with HSV-1 and HSV-2 immunostains and displayed a lymphoplasmacytic infiltrate. The patient received foscarnet and imiquimod for two weeks with minimal improvement. Based on the previous activity of leflunomide, which has both antiviral and immunomodulatory properties, in cytomegalovirus and herpes simplex infections, leflunomide 20 mg orally twice daily was started. The patient received 23 days of foscarnet, 14 days of topical imiquimod, and 11 days of leflunomide with approximately 80% reduction in the size of the perineal lesion. After nine months on leflunomide there was complete regression of the large perineal lesion and only two small ulcerations remained on the scrotum. Pseudotumoral herpes lesions in HIV patients represent an immune reconstitution event and are poorly responsive to the usual anti-herpes agents. This report demonstrates the successful use of leflunomide in the treatment of an HIV patient with pseudotumoral herpes. Thalidomide has also been used with some success.

Clinical Characteristics and Outcomes of HIV-Infected Patients with Non-AIDS Defining Cancers in a National Institute Cancer in Mexico

Background Non-AIDS Defining Cancers (NADCs) have been recognized as an increasing cause of morbidity and mortality in HIV patients, related mainly to co-infections and/or lifestyle risks. There is no data of NADCs prevalence in Mexico. We describe type of NADCS, clinical characteristics and outcomes of HIV-infected individuals with NADCs.Methods We conducted a retrospective study of 1126 patients attending the HIV/AIDS Clinic at Instituto Nacional de Cancerología in Mexico city (a tertiary care center for adult patients with cancer), since 1996 to December 2016, who had confirmed NADCs after HIV diagnosis. Demographic and clinical data were collected for all HIV patients with NADCs.ResultsOver 1126 HIV-positive individuals seen at the INCan, 139 (12.3%) patients developed a NADC, five patients developed two NADCs during their follow-up, 114 (82%) were male. The median age at diagnosis of NADCs was 42.4 ± 10.9 years, the median of CD4 was 354.4 cell/mm at that time of NADCs, 81 of them (56.3%) had a CD4 count >200 cell/mm3, 81 (56.3%) had undetectable HIV viral load. In males the distribution of NADCS was 36 (25%) Hodgkin’s lymphoma (HL), 16 (11.1%) anal cancer, 13 (9%) germinal tumors males, and two lung cancers, and in females: 11 (7.7%) vulvo-vaginal, seven (4.9%) breast cancer, four (2.8%) thyroid cancer and one case of Hodgkin’s lymphoma. The median of follow-up of NADCs was 2.5 (IQR 0.4,3.6) years. Nine patients died attributable to NADCs and 51 patients lost of follow-up.Conclusion HL was the most frequent NADC on men as it has been described in other reports, followed by anal cancer. In women vulvo-vaginal cancers were the most frequent. These three malignances are related with viral etiology. Lung cancer was uncommon, different from that described in the US population, smoking is less frequent in the HIV Mexican population. NADCS can occur at any stage of HIV infection, regardless of immune status.Disclosures All authors: No reported disclosures.

A2 to B Blood Type Incompatible Deceased Donor Kidney Transplantation in a Recipient Infected with the Human Immunodeficiency Virus: A Case Report

BackgroundWith the introduction of the Kidney Allocation System in the United States in December 2014, transplant centers can list eligible B blood type recipients for A2 organ offers. There have been no prior reports of ABO incompatible A2 to B deceased donor kidney transplantation in human immunodeficiency virus-positive (HIV+) recipients to guide clinicians on enrolling or performing A2 to B transplantations in HIV+ candidates. We are the first to report a case of A2 to B deceased donor kidney transplantation in an HIV+ recipient with good intermediate-term results. Methods and ResultsWe describe an HIV+ 39-year-old African American man with end-stage renal disease who underwent A2 to B blood type incompatible deceased donor kidney transplantation. Prior to transplantation, he had an undetectable HIV viral load. The patient was unsensitized, with his most recent anti-A titer data being 1:2 IgG and 1:32 IgG/IgM. Induction therapy of basiliximab and methylprednisolone was followed by a postoperative regimen of plasma exchange, intravenous immunoglobulin, and rituximab with maintenance on tacrolimus, mycophenolate mofetil, and prednisone. He had delayed graft function without rejection on allograft biopsy. Nadir serum creatinine was 2.0 mg/dL. He continued to have an undetectable viral load on the same antiretroviral therapy adjusted for renal function. ConclusionsTo our knowledge, this is the first report of A2 to B deceased donor kidney transplantation in an HIV+ recipient with good intermediate-term results, suggesting that A2 donor kidneys may be considered for transplantation into HIV+ B-blood type wait list candidates.

Statin drugs decrease progression to cirrhosis in HIV/hepatitis C virus coinfected individuals.

Chronic HIV/hepatitis C virus (HCV) coinfection carries increased risk of cirrhosis, hepatocellular carcinoma, and death. Due to anti-inflammatory properties, 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) inhibitors (statins) may be useful adjunctive therapy to reduce liver disease progression. Clinical information was extracted from the Veterans Affairs HIV and HCV Clinical Case Registries (1999-2010). HIV-related variables included combination antiretroviral therapy era of diagnosis, CD4 cell count, and percentage time with undetectable HIV viral load. Metabolic variables included diabetes, low high-density lipoprotein (HDL), and hypertension. Statin use was measured as percentage time with active prescription (time-updated throughout the follow-up period). Cox proportional hazards analysis was used to determine risk factors for cirrhosis (International Classification of Diseases-9 or aminotransferase-to-platelet ratio index >2) overall and in groups stratified by alanine aminotransferase (ALT) level above and below 40 IU/l. The cohort included 5985 HIV/HCV coinfected veterans. The majority was black race, and the mean age at index date was 45 years. Statin use was significantly protective of cirrhosis for patients with ALT 40 IU/l or less; for every 30% increase in time on statin, there was a 32% decreased risk of developing cirrhosis (hazard ratio 0.68, 95% confidence interval 0.47-0.98). Diabetes and low HDL were significantly associated with cirrhosis in patients with ALT greater than 40 IU/l (hazard ratio 1.15, P < 0.04 and hazard ratio 1.3, P < 0.0001). Statin drug use is beneficial in mitigating the risk of liver disease progression for HIV/HCV coinfected patients without advanced liver disease. Low HDL and diabetes in coinfected patients with abnormal ALT have greater risk of cirrhosis development.

Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression: A prospective cohort study.

Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant.We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR <50 copies/mL) and a snapshot analysis at 48, 96, and 144 weeks. Virological failure (VF) was defined as confirmed pVL >50 copies/mL.We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50 copies/mL. The third drug in the previous regimen was ritonavir-boosted atazanavir (ATV/r) in 79 (28%), and another ritonavir-boosted protease inhibitor (PI/r) in 29 (10%). Ninety (32%) had previously failed with a PI. Proportions of people with virological success at 48/96/144 weeks were 90%/87%/88% (TLOVR) and 74%/67%/59% (snapshot analysis), respectively. The rates of VF were 8%/8%/6%. Rates of adverse events leading to study discontinuation were 0.4%/1%/2%. The multivariable adjusted analysis showed an association between VF and nadir CD4+ (hazard ratio [HR] 0.63 [95% confidence interval [CI]: 0.42–0.93] per 100 cells higher), time with pVL ≤50 copies/mL (HR 0.87 [95% CI: 0.79–0.96] per 6 months longer), and previous failure with a PI (HR 2.78 [95% CI: 1.28–6.04]). Resistance selection at failure was uncommon.A switch to ATV + ABC/3TC in selected subjects with suppressed viremia was associated with low rates of VF and discontinuation due to adverse events, even in subjects not receiving ATV/r. The strategy might be considered in those with long-term suppression and no prior PI failure.

Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial

AbstractAutologous hematopoietic cell transplant (AHCT) for HIV-infected patients is largely limited to centers with HIV-specific expertise. The Blood and Marrow Transplant Clinical Trials Network 0803/AIDS Malignancy Consortium 071 trial is a multicenter phase 2 study of AHCT for patients with HIV-related lymphoma (HRL). Eligible patients had chemotherapy-sensitive relapsed/persistent HRL, were >15 years of age, and had treatable HIV infection. Patients were prepared using carmustine, etoposide, cytarabine, and melphalan and received consistent management of peritransplant antiretroviral treatment. The primary endpoint was 1-year overall survival. Forty-three patients were enrolled; 40 underwent AHCT. Pretransplant HIV viral load was undetectable (<50 copies/mL) in 32 patients (80%); the median CD4 count was 249/μL (range, 39-797). At a median follow-up of 24.8 months, 1-year and 2-year overall survival probabilities were 87.3% (95% confidence interval [CI], 72.1-94.5) and 82% (95% CI, 65.9-91), respectively. The probability of 2-year progression-free survival was 79.8% (95% CI, 63.7-89.4). One-year transplant-related mortality was 5.2%. Median time to neutrophil and platelet recovery was 11 days and 18 days, respectively. Nine patients experienced a total of 13 unexpected grade 3-5 adverse events posttransplant (10 grade 3 and 3 grade 4 events). Twenty-two patients had at least 1 infectious episode posttransplant. At 1 year post-AHCT, median CD4+ T-cell count was 280.3 (range, 28.8-1148.0); 82.6% had an undetectable HIV viral load. Trial patients were compared with 151 matched Center for International Bone Marrow Transplant Research controls. Outcomes between HIV-infected patients and controls were not statistically significantly different. HRL patients should be considered candidates for AHCT if they meet standard transplant criteria. The trial was registered at www.clinicaltrials.gov as #NCT01141712.

Randomized Controlled Trial: 4 Month versus 6 Month Monitoring of HIV-infected Patients on Highly Active Antiretroviral Therapy.

As HIV treatment becomes more widely available and efficacious, and persons with HIV live longer, considerations for the financial and healthcare impact are of important. The best interval for routine HIV monitoring has been identified as area in which gaps in knowledge exist. The goal of this study is to determine the impact of changing scheduled follow up care for persons with HIV from a 4 to 6months interval. HIV infected adults with a CD4 count ≥250cells/μl, and an undetectable HIV viral load (VL) by an ultrasensitive assay for at least 1year were randomized to routine HIV care at either a 4 or 6months interval. Subjects were monitored for virological failure, adherence and quality of life (QOL). 142 subjects were enrolled and completed study protocol. Two subjects in the 6months arm developed virological failure, p value=0.5. There was no difference in adherence, or QOL scores. Subjects in the 4months arm had higher rates of HIV visits (8.5/100 vs. 5.2/100 person months, p=0.01) and non-HIV related visits (9.4/100 vs. 6.0/100person months, p=0.01) and were more likely to change antiretroviral regimen (34.8 vs. 15.8%, p=0.01). Despite strict inclusion criteria in this relatively short follow up time, 2/142 (1.4%) subjects developed virological failure and many more had transient detectable VL. While not statistically significant a larger study with longer follow up is needed.

Supporting Treatment Adherence Readiness through Training (START) for patients with HIV on antiretroviral therapy: study protocol for a randomized controlled trial

BackgroundFew HIV antiretroviral adherence interventions target patients before they start treatment, assess adherence readiness to determine the timing of treatment initiation, or tailor the amount of adherence support. The Supporting Treatment Adherence Readiness through Training (START) intervention, based on the information-motivation-behavioral skills model of behavior change, is designed to address these gaps with the inclusion of (1) brief pill-taking practice trials for enhancing pretreatment adherence counseling and providing a behavioral criterion for determining adherence readiness and the timing of treatment initiation and (2) a performance-driven dose regulation mechanism to tailor the amount of counseling to the individual needs of the patient and conserve resources. The primary aim of this randomized controlled trial is to examine the effects of START on antiretroviral adherence and HIV virologic suppression.Methods/designA sample of 240 patients will be randomized to receive START or usual care at one of two HIV clinics. Primary outcomes will be optimal dose-taking adherence (>85 % prescribed doses taken), as measured with electronic monitoring caps, and undetectable HIV viral load. Secondary outcomes will include dose-timing adherence (>85 % prescribed doses taken on time) and CD4 count. Primary endpoints will be month 6 (short-term effect) and month 24 (to test durability of effect), though electronic monitoring will be continuous and a fully battery of assessments will be administered every 6 months for 24 months.DiscussionIf efficacious and cost-effective, START will provide clinicians with a model for assessing patient adherence readiness and helping patients to achieve and sustain readiness and optimal treatment benefits.Trial registrationClinicalTrials.gov identifier NCT02329782. Registered on 22 December 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1287-3) contains supplementary material, which is available to authorized users.

CD4/CD8 ratio as a predictor of the response to HBV vaccination in HIV-positive patients: A prospective cohort study

BackgroundHepatitis B virus (HBV) and human immunodeficiency virus (HIV) share transmission mechanisms and thus coinfection is frequent. Active immunization against HBV is essential in HIV patients. Reports using standard and reinforced HBV vaccination schedules vary widely in seroconversion rates depending on the characteristics of the included patients. Regional data concerning HBV vaccination in HIV patients are scarce. We aim to determine the serological response to HBV vaccination using standard schedule in HIV-positive patients and to evaluate characteristics that predict seroconversion. Materials and methodsWe performed a single centre prospective study of HBV vaccination with standard schedule in HIV-positive patients. Adults with negative markers of HBV infection were included between November 2012 and December 2014. Anti-HBs titres were measured 4–8 weeks after completion of vaccination schedule. Clinical, laboratory values and HIV characteristics were analyzed to determine their association with seroconversion and adherence to the HBV vaccination schedule. ResultsThe study included 245 HIV-positive patients, 68.9% were male and the mean age was 42.1 years. A total of 80.7% of the patients had undetectable HIV viral loads, 86.1% had CD4 counts >200, and 94.7% were on HAART. The response to vaccination was positive in 62% (95% CI, 56–68%) and mean anti-HBs titres of 646IU/ml. 85.5% of the responders had anti-HBs titres >100IU/ml. An age less than 45 years, no tobacco use and a CD4/CD8 ratio >0.4 were associated with seroconversion in multivariate analysis. The seroconversion rates were 86% in the subgroup of patients who met these criteria. A total of 97.9% of the study population completed the vaccination schedule. ConclusionThe CD4/CD8 ratio was the primary factor associated with positive serological conversion in the multivariate analysis. The seroconversion rates were higher in a selected group of patients who were particularly suitable for the use of the standard HBV vaccination schedule.

Efficacy and safety of switching to abacavir/lamivudine (ABC/3TC) plus rilpivirine (RPV) in virologically suppressed HIV-infected patients on HAART.

We analysed the efficacy and safety of switching from a regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTI) or integrase inhibitors (INI) to ABC/3TC + RPV in virologically suppressed HIV-infected patients. This multicentre, retrospective study comprised asymptomatic HIV-infected patients who switched from 2 NRTI + NNRTI or 2 NRTI + INI to ABC/3TC + RPV between February 2013 and December 2013; all had undetectable HIV viral load prior to switching. Efficacy and safety, and changes in lipids and cardiovascular risk (CVR) were analysed at 48 weeks. Of 85 patients (74.1 % men, mean age 49.5 years), 83 (97.6 %) switched from a regimen based on NNRTI (EFV 74, RPV 5, ETV 2, NVP 2), and 45 (53 %) switched from TDF/FTC to ABC/3TC. The main reasons for switching were toxicity (58.8 %) and convenience (29.4 %). At 48 weeks, 78 (91.8 %) patients continued taking the same regimen; efficacy was 88 % by intention to treat, and 96 % by per protocol. Two patients were lost to follow-up and five ceased the new regimen (4 due to adverse effects and 1 virologic failure). Mean CD4 cell counts increased (744 vs. 885 cells/μL; p = 0.0001), and there were mean decreases in fasting total cholesterol (-15.9 mg/dL; p < 0.0001) and LDL-cholesterol (-11.0 mg/dL; p < 0.004), with no changes in HDL-cholesterol, triglycerides, total cholesterol:HDL-cholesterol ratio, and CVR. ABC/3TC + RPV is effective and safe in virologically-suppressed patients on antiretroviral therapy (ART). Forty-eight weeks after switching the lipid profile improved with decreases in total and LDL cholesterol.

Molecular Characterisation and HIV Drug Resistance Patterns of HIV-1 Variants in Plasma and Peripheral Blood Mononuclear Cells Sample Pairs

Objective: Plasma is currently the specimen of choice for routine HIV drug resistance (HIVDR) testing. However, HIV compartmentalization has been well documented in different reservoirs, including peripheral blood mononuclear cells (PBMCs). We molecularly characterized paired plasma and PBMC sample pairs and compared their HIVDR mutation patterns. Methods: To compare HIVDR mutation patterns in plasma and PBMC sample pairs, whole blood was collected for plasma and PBMC isolation from 43 treatment-naive and 10 treatment-experienced individuals, and HIVDR profiles determined by sequencing the pol gene. Treatment-naive individuals were initiated on Efavirenz/Emtricitabine/ Tenofovir fixed dose combination therapy and follow up HIV-1 viral loads were performed after at least 6 months of treatment. Results: HIVDR mutation prevalence in the treatment-naive group was 5.1% in plasma samples compared to 10.3% when both plasma and PBMC sequences were considered. Variable amino acid positions were detected in 21% and 12% of the protease and reverse transcriptase genes, respectively. These were generally not in HIVDR positions and did not form signature patterns. The subset of patients with additional resistance associated sequence variations detected in PBMCs had undetectable HIV-1 viral loads after at least 6 months of anti-retroviral therapy. Conclusions: The sequencing of paired plasma and PBMC specimens provided additional HIVDR data which were not detected when only plasma samples were tested. However the resistant variants detected in the PBMCs did not seem to negatively affect treatment outcome at 6 months as viral suppression was achieved. These data highlight proviral HIVDR mutations in HIV infected individuals and longer follow up on patients on treatment may be needed to determine their clinical impact.

Association between Time on Protease Inhibitors and the Incidence of Squamous Cell Carcinoma of the Anus among U.S. Male Veterans.

Protease inhibitors (PIs) have been shown to have anti-tumor activity in addition to their antiretroviral properties. We sought to assess the association between PI use and the incidence of squamous cell carcinoma of the anus (SCCA) in HIV-infected individuals. We performed a retrospective cohort study among male US veterans diagnosed with HIV who were diagnosed between 1985 and 2010, using the Veterans Affairs HIV Clinical Case Registry (CCR). We calculated hazards ratios associated with PI use (both as percent time on PI and as 12-month intervals of PI use), utilizing time-dependent Cox models. We adjusted for risk factors, including age, race, year of enrolment into CCR, recent and nadir CD4, and percent time undetectable HIV viral load. A total of 28, 886 HIV-infected men met inclusion criteria. Of these, 373 were newly diagnosed with SCCA during the study period. In multivariate analysis, increasing percent time on PIs was associated with an increased risk of SCCA (aHR 1.07; 95% CI = 1.03–1.10 per 10% increase in time on PI). Poor immunologic recovery and virologic control, a history of condylomata acuminata, and CCR enrolment in the late combined antiretroviral therapy era were also associated with increased SCCA risk. Increasing percent time on a PI-based combined antiretroviral therapy regimen may be associated with an increased risk of developing SCCA in HIV-infected male US veterans. Future studies, better accounting for HIV control and treatment compliance, are necessary to further clarify this association.

Central nervous system penetration effectiveness of antiretroviral drugs and neuropsychological impairment in the Ontario HIV Treatment Network Cohort Study.

Since the introduction of combination antiretroviral therapy (cART), the incidence of severe HIV-associated neurocognitive impairment has declined significantly, whereas the prevalence of the milder forms has increased. Studies suggest that better distribution of cART drugs into the CNS may be important in reducing viral replication in the CNS and in reducing HIV-related brain injury. Correlates of neuropsychological (NP) performance were determined in 417 participants of the Ontario HIV Treatment Cohort Study (OCS). All participants were on three cART drugs for at least 90days prior to assessment. Multiple logistic and linear regression methods were used. Most participants were Caucasian men with mean age of 47years. About two thirds had a nadir CD4+ T-cell count below 200cells/μL and 92% had an undetectable plasma HIV viral load. The median CNS penetration effectiveness (CPE) score was 7. Sixty percent of participants had neuropsychological impairment. Higher CPE values significantly correlated with lower prevalence of impairment in bivariate and multivariate analyses. In this cross-sectional analysis of HIV+ adults who had a low prevalence of comorbidities and were taking three-drug cART regimens, greater estimated distribution of cART drugs into the CNS was associated with better NP performance.

Marijuana use and undetectable HIV viral load in persons living with HIV in Florida

Aims: Sexual violence towardsmen bywomen has been grossly understudied in the literature. Moreover, the tactics used to force sex amongmen is virtually unknown. The aimswere to investigate: (1) the tactics used to force men to have sex and (2) the role of substance use on forced sex and the tactics employed. Methods: I used data from the National Survey for Family Growth (2006–2010) to investigate the association between forced sex and substance use among men who reported forced sex by a woman and the association between tactic used during the sexual attack and substance use in the last year. Six tactics were ranked according to force exhorted: given drugs/alcohol, bigger/older, threats to relationship, threaten physical harm, held down, physically hurt. The analytic sample was 8,108 and I used logistic regression to test the hypotheses. Results: Five percent of men (N=501) reported forced sex by a woman. The top 3 tactics endorsed were verbal pressure (69%), given drugs/alcohol (38%), and being held down (32%). Results indicate a difference in rates of marijuana use (p=0.02), crack use (p<0.001), crystal meth use (p<0.001) and a marginal difference for binge drinking (p=0.058) between men who reported forced sex and those who did not. Being given drugs or alcohol as a means of forced sex was associated with binge drinking (OR=1.76) and cocaine use (OR=3.04). Being held downwas associated withmarijuana (OR=2.04) and cocaine use (OR=2.89). Conclusions: Men who reported forced sex had higher rates of substance use compared to men with no forced sex history. Although substance use was associated with force tactics at statistically significant levels, a clear trend of stronger tactics being associatedwith substanceusewasnot observed. Longitudinal analysis of sexual practices should be conducted to better understand the role of alcohol/drug consumption preceding a forced sex event and to examine whether there is a cycle in which substance use increases risk of future sexual violence and thus violence increases risk of substance use among men. Financial support: 5T32DA00727222.

Persistent subclinical immune defects in HIV-1-infected children treated with antiretroviral therapy.

With the introduction of combined antiretroviral therapy (cART), HIV-infected children can reach adulthood with minimal clinical complications. However, long-term HIV and cART in adults are associated with immunosenescence and end-organ damage. Long-term consequences of HIV and cART in children are currently unknown. We studied 69 HIV-infected children and adolescents under cART (0-23 years) for the occurrence of subclinical immunological aberrations in blood B and T cells, using detailed flow cytometric immunophenotyping and molecular analyses. Children with undetectable plasma HIV viral loads for more than 1 year showed near-normal to normal CD4 T-cell numbers and near-normal numbers of most class-switched memory B cells. Furthermore, expansions of aberrant CD21 B cells contracted in patients with virus suppression. In contrast, CD8 effector T cells were increased, and CD4 memory T cells, Vγ9Vδ2 T cells and CD27IgA memory B cells were decreased and did not normalize under ART. Moreover, Vγ9Vδ2 T cells showed defects in their T-cell receptor repertoire selection. Our results show the effectiveness of current cART to enable the build-up of phenotypically diverse B-cell and T-cell memory in HIV-infected children. However, several subclinical immune abnormalities were detected, which were partially caused by defective immune maturation. These persistent abnormalities were most severe in adolescents and therefore warrant long-term follow-up of HIV-infected children. Early identification of such immune defects might provide targets for monitoring future treatment optimization.