Plasma HIV Viral Load Research Articles

Left out but not forgotten: Should closer attention be paid to coinfection with herpes simplex virus type 1 and HIV?

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are among the most common coinfections seen in individuals infected with HIV-1. Most research on HSV-HIV coinfection has focused on HSV-2, and in particular, on its impact on HIV transmission. HSV-2 is associated with micro- and macroulcerations in genital mucosal surfaces, increased numbers of HIV target cells in genital mucosal tissue and increases in plasma HIV viral load of up to 0.5 log(10) copies/mL, such that HSV-2 infection increases the risk of both HIV acquisition and transmission. Because plasma HIV RNA levels are a major determinant of rates of CD4 cell decline, HSV-2 coinfection may also adversely affect the progression of HIV disease. Anti-HSV medications have in fact been associated with reciprocal decreases in HIV viral load in short-term studies. These findings have led to the development of several clinical trials of HSV-2 suppression as strategies for preventing HIV transmission and slowing the rate of HIV disease progression. HSV-1 coinfection has largely been ignored from this growing body of research, yet there are several reasons that this coinfection remains an important issue for study. First, the seroprevalence of HSV-1 is consistently higher than that of HSV-2 among both HIV-infected and HIV-uninfected populations, underscoring the relevance of HSV-1 coinfection to the majority of HIV-infected persons. Second, pre-existing HSV-1 antibodies in individuals may modulate the course of subsequently acquired HSV-2 infection; the implications of such changes on HSV-HIV coinfection remain unexplored. Third, HSV-1 and HSV-2 are closely related viruses that share 83% genetic homology. Their virological and pathobiological similarities suggest that their implications on HIV pathogenesis may be similar as well. Finally, HSV-1 is becoming increasingly relevant because the incidence of genital HSV-1 has risen. Although genital herpes is traditionally associated with HSV-2, recent studies have shown that the majority of serologically confirmed primary genital herpes in some settings is attributable to HSV-1. Because the genital tract is an important site of biological interaction between HSV and HIV, this epidemiological change may be clinically important.

P.051 Performances and comparative evaluation of the automated VERSANT® HIV-1 RNA 1.0 kinetic PCR molecular system (kPCR) for the quantification of HIV-1 plasma viral load

P.051 Performances and comparative evaluation of the automated VERSANT® HIV-1 RNA 1.0 kinetic PCR molecular system (kPCR) for the quantification of HIV-1 plasma viral load

High Prevalence of Antiretroviral Drug Resistance Mutations in HIV-1 Non-B Subtype Strains From African Children Receiving Antiretroviral Therapy Regimen According to the 2006 Revised WHO Recommendations

High Prevalence of Antiretroviral Drug Resistance Mutations in HIV-1 Non-B Subtype Strains From African Children Receiving Antiretroviral Therapy Regimen According to the 2006 Revised WHO Recommendations

Excellent Immune Recovery Following the Intensive Chemotherapy CODOX-M/IVAC, An Effective Therapy for HIV-Associated Burkitt's Lymphoma (BL)

Background and aim: The outcome of patients with HIV-associated Burkitt's lymphoma (HIV-BL) treated with infusional regimens remains poor, even in the highly active anti-retroviral (HAART) era. In contrast, promising results have been published in HIV-BL with the same intensive chemotherapies used in the non-HIV population. However, scarce data on immunological recovery following these regimens are available. The objective of this multicentre study was to analyse the outcome of patients with HIVBL treated with the intensive chemotherapy regimen CODOX-M/IVAC and HAART, with a particular emphasis on the analysis of immunological recovery after treatment.Patients and methods: 29 patients (22 male; median age: 38) from 3 UK centres consecutively treated with CODOX-M/IVAC from 2003 to 2008 were included in the study. CODOX-M/IVAC consisted of 2 alternating cycles of CODOX-M (cyclophosphamide 800mg/sqm day 1 and 200mg/sqm days 2–5, doxorubicin 40mg/sqm day 1, vincristine 1.5mg/sqm days 1 and 8, methotrexate 3g/sqm day 10) and IVAC (etoposide 60mg/sqm days 1–5, ifosfamide 1g/sqm days 1–5, cytarabine 1g/sqm bd days 1 and 2) for patients with high-risk disease and 3 cycles of CODOX-M for patients with low-risk disease. High-risk disease was defined by the presence of at least 2 of the following: stage III–IV, ECOG≥2, extranodal sites≥2 or high serum LDH. All patients received concomitant treatment with HAART (NRTI + NNRTI: 21; NRTI + PI: 8) and prophylactic antimicrobials as well as intrathecal prophylaxis and G-CSF as per protocol. Four patients received rituximab in combination with the chemotherapy. Lymphocyte subsets and plasma HIV-1 viral load (VL) were measured during chemotherapy and at 3-month intervals during follow-up.Results: HIV was diagnosed concomitantly with BL in 12 patients. The median CD4 count at BL diagnosis was 167/mm3 (range: 4–848), with CD4>200/mm3 in 41% of patients and VL being undetectable in 5 (18%) patients. Eight (28%) of the patients previously known to have HIV infection were on HAART before the diagnosis of BL. The majority of the patients (72%) had high-risk disease. Twenty patients (69%) were diagnosed in advanced stage (III–IV), with bone marrow (BM) involvement in 6 (21%) and central nervous system (CNS) infiltration in 5 (17%). The International Prognostic Index (IPI) was high (3–5) in 14 (48%) patients. Grade 3–4 non haematological toxicity was as follows: infection, 66% of the cycles; mucositis, 12%; and diarrhoea, 13%. Nine patients died during treatment, due to disease progression in 3 cases, toxicity in 5 (3 infections, 2 GI bleeding) and 1 patient died with a CNS lesion that was not biopsed. Response at the end of treatment amongst 23 assessable patients was as follows: complete response (CR)/CR uncertain (CRu): 16 patients (69%); partial response (PR): 4 (17%); progression: 3 patients (13%). After a median follow-up of 17 months (range: 9–67), 17 of 20 responding patients remain alive without disease progression, whilst 2 patients (1 CR, 1 PR) relapsed at 2 and 1 months after finishing treatment and died. One HAART non-compliant patient died in CR of HIV-related causes. Three patients in PR at the end of treatment survive without evidence of disease progression at 28, 37 and 51 months. Overall survival (OS) and disease-free survival (DFS) at 3 years were 49% and 70% respectively. Blood samples for immune recovery analyses were available for the majority of the patients during follow-up (81% 6 months after finishing chemotherapy, 86% at 12 and 24 months). VL was undetectable in 85% and CD4>200/mm3 in 53% of assessable patients 6 months after completing chemotherapy.Time (no. patients at risk)% CD4>200/mm3VL undetectableno./no. assessed%no./no. assessed%At BL diagnosis (29)12/29415/28181 month after finishing chemotherapy (21)5/172910/15676 months after finishing chemotherapy (16)8/155311/138512 months after finishing chemotherapy (14)9/127510/1283Conclusions: This retrospective analysis demonstrates that the intensive regimen CODOX-M/IVAC is feasible and effective in HIV positive patients on HAART with BL. Immunological recovery after treatment, not previously reported after such intensive chemotherapy, is excellent. Whether concomitant treatment with rituximab will improve outcome warrants further study.

Rosuvastatin, Pravastatin, and Atorvastatin for the Treatment of Hypercholesterolaemia in HIV-Infected Patients Receiving Protease Inhibitors

Highly active antiretroviral therapy (HAART) including protease inhibitors (PIs) has been independently associated with an abnormal lipid profile, and recent studies have shown an increased risk of cardiovascular complications in patients with prolonged exposure to HAART. Aim of our open-label, randomized, prospective study is to evaluate the role of different statins in the management of PI-associated hypercholesterolaemia. Ninety-four adult patients on a stable PI-based antiretroviral therapy since at least 12 months, and presenting hypercholesterolaemia (total cholesterol level >250 mg/dL) of at least 3-month duration and unresponsive to a hypolipidaemic diet and physical exercise, were randomized to a hypolipidaemic treatment with rosuvastatin (10 mg once daily), pravastatin (20 mg once daily) or atorvastatin (10 mg once daily), and were followed-up for 12 months. Among the 85 subjects who completed the study, rosuvastatin was employed in 26 cases, pravastatin in 31, and atorvastatin in 28. At the close of 1-year follow-up, statins led to a mean reduction of 21.2% and 23.6% versus baseline total cholesterol and LDL cholesterol levels, respectively (p=0.002). Mean decrease in total cholesterol concentration was significantly greater with rosuvastatin (25.2%) than with pravastatin (17.6%; p=0.01) and atorvastatin (19.8%; p=0.03). During these 12 months, all administered statins showed a favourable tolerability profile, and patients' plasma HIV viral load did not present any variation. All used statins showed a significant efficacy and a good tolerability in the treatment of diet-resistant hyperlipidaemia, but rosuvastatin was found to be more effective in reducing total and LDL cholesterol levels.

Abacavir-induced febrile agranulocytosis and anaemia

Abacavir-induced febrile agranulocytosis and anaemia

Monitoring of primary HIV-1 genotypic drug-resistance and HIV-1 subtype in 237 antiretroviral treatment-naive HIV/AIDS patients in China

Objective To investigate the prevalence of primary HIV-1 genotype drug-resistance and viral subtype from 237 treatment-naive patients in China.nethods CD4+ T cell counts,plasma HIV-1 viral load and HIV-1 gene sequencing in total 237 treatment-naive patients enrolled from 20 provinces/regions were detected for the evaluation of primary HIV genotypic drug-resistance.Results The survey of 237 treatment-naive patients from muhicenter areas including Henan Province,Yunan Province,and Shanghai showed that 9 subtypes of HIV-1 strains were finally identified.Most of patients were infected before 2003.Only 3 cases had genotypic mutations associated resistance to antiretroviral drugs,with high resistance to nucleoside reverse transcriptase inhibitors(NRTIs),moderate resistance to protease inhibitors(PIs)and high resistance to non-nucleoside reverse transcriptase inhibitors(NNRTIs).respectively.The prevalence of primary genotypic drug resistance was 1.3%(3/237)in this study.Conclusions The rate of HIV-1 primary genotypic drug-resistance is still relatively low in treatment-naive HIV/AIDS patients while 9 subtypes of HIV-1 strain was diseovered. Key words: Human immunodeficiency virus(HIV); Primary; Drug resistance; Protease; Reverse transcriptase; Subtype

Mucosal Neisseria gonorrhoeae coinfection during HIV acquisition is associated with enhanced systemic HIV-specific CD8 T-cell responses

The host immune response against mucosally acquired pathogens may be influenced by the mucosal immune milieu during acquisition. As Neisseria gonorrhoeae can impair dendritic cell and T-cell immune function, we hypothesized that coinfection during HIV acquisition would impair subsequent systemic T-cell responses. Monthly screening for sexually transmitted infections was performed in high risk, HIV seronegative Kenyan female sex workers as part of an HIV prevention trial. Early HIV-specific CD8 T-cell responses and subsequent HIV viral load set point were assayed in participants acquiring HIV, and were correlated with the presence of prior genital infections during HIV acquisition. Thirty-five participants acquired HIV during follow-up, and 16 out of 35 (46%) had a classical sexually transmitted infection at the time of acquisition. N. gonorrhoeae coinfection was present during HIV acquisition in 6 out of 35 (17%), and was associated with an increased breadth and magnitude of systemic HIV-specific CD8 T-cell responses, using both interferon-gamma gamma and MIP-1 beta as an output. No other genital infections were associated with differences in HIV-specific CD8 T-cell response, and neither N. gonorrhoeae nor other genital infections were associated with differences in HIV plasma viral load at set point. Unexpectedly, genital N. gonorrhoeae infection during heterosexual HIV acquisition was associated with substantially enhanced HIV-specific CD8 T-cell responses, although not with differences in HIV viral load set point. This may have implications for the development of mucosal HIV vaccines and adjuvants.

HIV infection in refugees: a case–control analysis of refugees in Rhode Island

The number of HIV-infected refugees entering the USA is increasing. There is little data describing the HIV-infected refugee population and the challenges encountered when caring for them. We performed a retrospective case-control analysis of HIV-infected refugees in order to characterize their co-morbidities, baseline HIV characteristics, and longitudinal care compared to HIV-infected non-refugees. A retrospective chart review was performed of HIV-infected refugees and non-refugees who were matched for gender, age, and time of establishment of initial HIV care. The refugee population studied was largely from West Africa. Refugees were more likely than non-refugees to have heterosexual risk for HIV infection, latent tuberculosis infection, and active hepatitis B. Refugees were less likely than non-refugees to have a history of substance use, start antiretrovirals, and be enrolled in a clinical study. The baseline CD4 counts and HIV plasma viral loads were similar between the two groups. Clinicians caring for West African HIV-infected refugees should be knowledgeable about likely co-morbidities and the impact of cultural differences on HIV care. Further studies are needed to develop culturally competent HIV treatment, education, and prevention programs for refugees who are beginning a new life in the USA.

Suppressive Acyclovir Therapy Reduces HIV Cervicovaginal Shedding in HIV- and HSV-2-Infected Women, Chiang Rai, Thailand

Herpes simplex virus type 2 infection is important in the HIV epidemic and may contribute to increased HIV transmission. We evaluated the effect of suppressive acyclovir therapy on cervicovaginal HIV-1 shedding. HIV-1- and herpes simplex virus type 2-coinfected women aged 18-49 years with CD4 counts >200 cells/microL were enrolled in a randomized crossover trial of suppressive acyclovir therapy (NCT00362596, http://www.clinicaltrials.gov). For each woman, monthly plasma and weekly cervicovaginal lavage specimens were collected; the mean of the monthly median cervicovaginal lavage HIV-1 viral load and plasma HIV-1 viral load was compared. Sixty-seven women were enrolled; at baseline, median CD4 count was 366 cells/microL, and median HIV-1 plasma viral load was 4.6 log10 copies/mL. The mean cervicovaginal lavage HIV-1 viral load was 1.9 (SD 0.8) log10 copies/mL during the acyclovir month and 2.2 (SD 0.7) log10 copies/mL during the placebo month (P < 0.0001); the mean decrease in HIV was 0.3 log10 copies/mL. The mean plasma HIV viral load during the acyclovir month (3.78 log10 copies/mL) was reduced compared with the placebo month (4.26 log10 copies/mL, P < 0.001). Acyclovir reduced HIV genital shedding and plasma viral load among HIV-1- and herpes simplex virus type 2-coinfected women. Further data from clinical trials will examine the effect of suppressive therapy on HIV transmission.

Elvitegravir: An Emerging HIV Integrase Inhibitor

Integration of the reverse transcribed HIV dsDNA into the host cell chromosome is critical for the subsequent production of progeny virions. In October 2007, the US FDA approved the first HIV-1 integrase inhibitor, raltegravir, as a therapeutic agent for treatment-experienced HIV-1-infected patients. Elvitegravir (GS-9137) is another HIV integrase inhibitor, which has a distinct chemical structure from raltegravir, and is currently being evaluated in HIV-1-infected patients. In Phase II clinical trials, elvitegravir combined with optimized background therapies significantly reduced the plasma HIV-1 viral load without serious adverse events up to 24 weeks. This article reviews the most recent available information on elvitegravir with respect to its clinical pharmacokinetics, pharmacodynamics and drug-resistance profile, and from the standpoint of extensive in vitro studies of its broad antiretroviral activity.

A randomised placebo-controlled trial to explore the effect of suppressive therapy with acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 among Zimbabwean sex workers

Objectives:To determine the effect of daily acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 (HSV-2) in a randomised placebo-controlled trial among rural Zimbabwean sex workers.Methods:214 women...

An unusual abacavir reaction

An unusual abacavir reaction

Risk factors for poor virological outcome at 12 months in a workplace-based antiretroviral therapy programme in South Africa: A cohort study

BackgroundReasons for the variation in reported treatment outcomes from antiretroviral therapy (ART) programmes in developing countries are not clearly defined.MethodsAmong ART-naïve individuals in a workplace ART programme in South Africa we determined virological outcomes at 12 months, and risk factors for suboptimal virological outcome, defined as plasma HIV-1 viral load >= 400 copies/ml.ResultsAmong 1760 individuals starting ART before July 2004, 1172 were in follow-up at 12 months of whom 953 (81%) had a viral load measurement (median age 41 yrs, 96% male, median baseline CD4 count 156 × 106/l). 71% (681/953) had viral load < 400 copies/ml at 12 months. In a multivariable analysis, independent predictors of suboptimal virological outcome at 12 months were <1 log decrease in viral load at six weeks (odds ratio [OR] 4.71, 95% confidence interval [CI] 2.56–8.68), viral load at baseline (OR 3.63 [95% CI 1.88–7.00] and OR 3.54 [95% CI 1.79–7.00] for 10,001–100,000 and >100,000 compared to <= 10,000 copies/ml, respectively), adherence at six weeks (OR 3.50 [95% CI 1.92–6.35]), WHO stage (OR 2.08 [95% CI 1.28–3.34] and OR 2.03 [95% CI 1.14–3.62] for stage 3 and 4 compared to stage 1–2, respectively) and site of ART delivery. Site of delivery remained an independent risk factor even after adjustment for individual level factors. At 6 weeks, of 719 patients with self-reported adherence and viral load, 72 (10%) reported 100% adherence but had <1 log decrease in viral load; conversely, 60 (8%) reported <100% adherence but had >= 1 log decrease in viral load.ConclusionVirological response at six weeks after ART start was the strongest predictor of suboptimal virological outcome at 12 months, and may identify individuals who need interventions such as additional adherence support. Self reported adherence was less strongly associated but identified different patients compared with viral load at 6 weeks. Site of delivery had an important influence on virological outcomes; factors at the health system level which influence outcome need further investigation to guide development of effective ART programmes.

British HIV Association guidelines for HIV‐associated malignancies 2008

British HIV Association guidelines for HIV‐associated malignancies 2008

Maternal herpes simplex virus type 2 coinfection increases the risk of perinatal HIV transmission: possibility to further decrease transmission?

To evaluate the association between maternal herpes simplex virus type 2 seropositivity and genital herpes simplex virus type 2 shedding with perinatal HIV transmission. Evaluation of women who participated in a 1996-1997 perinatal HIV transmission prevention trial in Thailand. In this nonbreastfeeding population, women were randomized to zidovudine or placebo from 36 weeks gestation through delivery; maternal plasma and cervicovaginal HIV viral load and infant HIV status were determined for the original study. Stored maternal plasma and cervicovaginal samples were tested for herpes simplex virus type 2 antibodies by enzyme-linked immunoassay and for herpes simplex virus type 2 DNA by real-time PCR, respectively. Among 307 HIV-positive women with available samples, 228 (74.3%) were herpes simplex virus type 2 seropositive and 24 (7.8%) were shedding herpes simplex virus type 2. Herpes simplex virus type 2 seropositivity was associated with overall perinatal HIV transmission [adjusted odds ratio, 2.6; 95% confidence interval, 1.0-6.7)], and herpes simplex virus type 2 shedding was associated with intrapartum transmission (adjusted odds ratio, 2.9; 95% confidence interval, 1.0-8.5) independent of plasma and cervicovaginal HIV viral load, and zidovudine treatment. Median plasma HIV viral load was higher among herpes simplex virus type 2 shedders (4.2 vs. 4.1 log(10)copies/ml; P = 0.05), and more shedders had quantifiable levels of HIV in cervicovaginal samples, compared with women not shedding herpes simplex virus type 2 (62.5 vs. 34.3%; P = 0.005). We found an increased risk of perinatal HIV transmission among herpes simplex virus type 2 seropositive women and an increased risk of intrapartum HIV transmission among women shedding herpes simplex virus type 2. These novel findings suggest that interventions to control herpes simplex virus type 2 infection could further reduce perinatal HIV transmission.

HIV-1-infected patients from the French National Observatory experiencing virological failure while receiving enfuvirtide

We studied gp41 mutations associated with failing enfuvirtide salvage therapy. This multicentre study involved patients with HIV-1 plasma viral load (pVL) > 5000 copies/mL after at least 3 months of uninterrupted enfuvirtide therapy and with plasma samples available at inclusion (T0), at initial enfuvirtide failure (T1) and at last follow-up visit during continued failing enfuvirtide therapy (T2). The HR-1 and HR-2 domains of the gp41 gene were sequenced at T0, T1 and T2. Ninety-nine patients were enrolled. At baseline, the median pVL and CD4 cell count were 5.1 log copies/mL and 72 cells/mm(3), respectively. Based on the ANRS Resistance Group algorithm, the proportion of patients harbouring viruses with enfuvirtide resistance mutations increased significantly between T0 and T1. In the HR-1 domain, the V38A/M, Q40H, N42T, N43D and L45M mutations wereselected (P < 0.02). In the HR-2 domain, no mutations were significantly selected during the follow-up. None of the mutations was associated with a CD4 cell count increment. Mutations selected during failing enfuvirtide salvage therapy are mainly located in the HR-1 domain of the gp41 gene, between codons 38 and 45. No mutations were associated with an increase in the CD4 cell count.

Adherence to Antiretroviral Therapy Assessed by Drug Level Monitoring and Self-Report in Cameroon

To compare adherence to antiretroviral therapy using drug level monitoring and self-report and to explore the relation between these 2 methods and viral load measurements. Sixty patients received a fixed-dose combination of nevirapine, stavudine, and lamivudine in a clinical study in Cameroon. Adherence was assessed every 6 months until month 36 by nevirapine minimal plasma concentration and self-report. Plasma HIV-1 viral load was determined at the same time. Analyses included 159 complete observations. The proportion of patients labeled as "adherent" was significantly lower using nevirapine monitoring (88.7%, 95% confidence interval [CI]: 82.7 to 93.2) than self-report (97.5%, CI: 93.7 to 99.3; P = 0.002). Virologic failure was associated with the nevirapine concentration (adjusted odds ratio [aOR] = 4.43; P = 0.018) but not with the self-reported adherence (aOR = 0.84; P = 0.9). As compared with the virologic outcome, the sensitivity of nevirapine level monitoring for predicting inadequate adherence was 20.5%, the specificity was 91.7%, the positive predictive value was 44.4%, and the negative predictive value was 78.0%. For self-report, the respective values were 2.6%, 97.5%, 25.0%, and 75.5%. Drug level monitoring provided a more reliable estimate of adherence than self-report. This method could be used in research settings. Operational research is required to define how to improve the accuracy of the self-report method because it is the most feasible method in clinical practice.

Cinacalcet in HIV haemodialysis patients.

Sir, Cinacalcet HCL (MIMPARA®), a positive allosteric modulator of the calcium-sensing receptor (CaR) on the surface of the parathyroid glands, reduces serum parathyroid hormone (PTH) levels in more than 80% of haemodialysis (HD) patients [1]. The efficacy and safety of cinacalcet has been demonstrated in several studies [1,2], but its use in HIV patients on chronic dialysis is not described. We report two HD patients with HIV infection treated simultaneously with anti-retroviral therapy and cinacalcet. A 24-year-old black woman was admitted in July 2002 for end-stage renal disease (ESRD) of unknown origin that required chronic HD. Simultaneously, HIV-1 infection was diagnosed. A tritherapy with efavirenz 600 mg, lamivudine 25 mg and didanosine 100 mg per day was initiated in January 2004, resulting in sustained undetectable HIV plasma viral load and stable T4 levels (>550/mm3). Cinacalcet was started in May 2007 at 30 mg/day and progressively increased to 90 mg without any efficacy (intact parathyroid hormone (iPTH) > 1000 pg/ml). In December 2007, cinacalcet was stopped and a parathyroidectomy was performed. Histological examination revealed a bilateral parathyroid adenoma. Efavirenz residual serum concentration after surgery and cinacalcet withdrawal was 1.5 μg/ml (normal range: 1.1–4 μg/ml). A 45-year-old Caucasian man was treated by chronic HD for ESRD of unknown aetiology since July 2003. HIV-1 and hepatitis B virus (HBV) co-infection was discovered at the time of dialysis initiation. A combination of efavirenz 600 mg, lamivudine 50 mg, didanosine 125 mg per day and tenofovir 245 mg per week resulted in undetectable HBV and HIV plasma viral load with sustained stable T4 levels (>600/mm3). Because of high serum iPTH (>1000 pg/ml), cinacalcet was initiated in May 2007 at 30 mg per day and further increased to 120 mg in November 2007 without efficacy. Efavirenz mean residual serum concentration on three consecutive measurements under cinacalcet therapy (120 mg) was 1.3 ± 0.5 (SD) μg/ml. The two patients received concomitant treatment with sevelamer, calcium carbonate and vitamin D3 during cinacalcet therapy. In both the cases, tolerance of cinacalcet and anti-retroviral treatment was good. Monthly monitoring of pancreatic and liver enzymes and serum calcium levels was not modified. Analysis of the literature shows that more than 80% of HD patients on cinacalcet therapy achieve an ≥30% reduction in iPTH level from the baseline over 6 months [1]. In our cases, whereas cinacalcet was administered for more than 6 months, no effect on iPTH was observed despite increased cinacalcet dosage. Little is known about the pathophysiology of resistance to cinacalcet. A role for non-compliance to the drug was excluded in both the cases. Defective sensitivity of the parathyroid cell to the calcimimetic drug has been proposed. Additionally, a relative resistance to cinacalcet was demonstrated in the case of severe decreased expression of CaR in parathyroid glands [3]. In our cases, resistance to cinacalcet was likely the result of drug interaction. Cinacalcet is metabolized through cytochrome P450 (CYP) isoenzymes 3A4, 2D6 and 1A2. In vitro studies have demonstrated that cinacalcet is a potent inhibitor of CYP2D6. Additionally, data suggest that during concomitant treatment with cinacalcet, dose adjustment may be necessary for CYP3A4 and CYP1A2 inductors or inhibitors [4]. As the metabolism of lamivudine, didanosine and tenofovir do not involve CYP450, the culprit drug seems to be efavirenz. Efavirenz is metabolized via CYP450, particularly by 3A4 and 2B6 isoenzymes. Although efavirenz is an in vitro inhibitor for 2C9, 2C19, 3A4, 2D6 and 1A2 isoenzymes, it has been demonstrated in humans that efavirenz can be inductor for CYP450 enzymes and can also induce its own metabolism by this mechanism [5,6]. This enzymatic induction, especially for CYP3A4 isoenzyme, is probably responsible for most drug interactions with efavirenz. Despite the absence of a known pharmakokinetics interaction between cinacalcet and efavirenz, enzymatic induction of CYP3A4 metabolism by efavirenz is probably responsible for therapeutic failure of cinacalcet in the present cases. Unfortunately, this hypothesis could not be verified, as the measurement of the serum cinacalcet level is not currently available. However, a role for decreased numbers of CaR or defective sensitivity of parathyroid cells cannot be excluded. In summary, cinacalcet in HD patients with chronic HIV infection treated by efavirenz seems inappropriate. Nephrologists need to be aware of this rare potential interaction. Surgical parathyroidectomy should be recommended. Conflict of interest statement. None declared. The results presented in this paper have not been published previously in whole or part, except in abstract format.

Recovery of cellular immunity following chemotherapy for AIDS related non Hodgkin’s lymphoma

8582 Background: Late effects of chemotherapy on immunological parameters in AIDS-related systemic NHL have not been described. Methods: 105 consecutive patients were treated with infusional CDE chemotherapy and HAART and 68 survived more than 3 months following the chemotherapy. Their lymphocyte subsets and plasma HIV viral loads were measured at regular intervals for 2 years and values compared to baseline. Results: During chemotherapy, there were statistically significant falls in CD4 (helper T), CD8 (cytotoxic T) and CD19 (B) cell populations but no changes in the CD56 (natural killer) cell population. Amongst the 68 survivors, there were statistically significant increases in CD4, CD8, CD19 and CD56 populations during the first year of follow-up, compared to the values at the start of chemotherapy. The rises were most marked during the first 3 months of follow-up, and the median rise over the first year were +97 cells/mL for CD4, +318 cells/mL for CD8, +137 cells/mL for CD19 and +32 cells/mL for CD56. During the second year of follow-up further statistically significant rises were documented for CD4 and CD19 cell counts but not for CD8 or CD56 cell counts. Data are available for 43 patients at 2 years post chemotherapy and for these patients the median CD4 cell count rose from 165/mL (IQR: 62–252) at the start of chemotherapy to 270/mL (IQR: 174–445) 2 years after completing chemotherapy. At the start of chemotherapy only 27% patients had an undetectable HIV plasma viral load. This value rose to 69% at the completion of chemotherapy, to 79% at 3 months, 81% at 1 year and 90% at 2 years after completing chemotherapy. Much of the initial suppression of HIV viraemia is because 41% of the cohort were antiretroviral naïve and started HAART with their chemotherapy. During 244 years of follow-up following chemotherapy in these 68 survivors, 7 second primary tumours and 8 opportunistic infections were diagnosed. Conclusions: Chemotherapy and concomitant HAART for AIDS-related NHL does not cause prolonged suppression of lymphocyte subsets. These data should provide reassurance regarding the long term immunological consequences of chemotherapy in people with HIV. No significant financial relationships to disclose.