Fendrix® compared to Engerix® in HIV-infected patients nonresponding to initial- and re-vaccination schedule.

BACKGROUND: In HIV-infected patients, the immunogenicity of hepatitis B vaccines is impaired. In this randomised controlled study (RCT), we investigated the effect of Fendrix® versus double-dose Engerix® vaccination in previously non-responsive HIV-infected subjects. METHODS: Patients included those who were HIV-infected and non-responders to a primary (single-dose hepatitis B (HBV) vaccination) and a subsequent double-dose HBV revaccination schedule. Subjects were randomised 1:1 to receive Fendrix® (t = 0, 4, 8, 24 weeks) or double-dose Engerix® (t = 0, 4, 24 weeks) vaccinations. Primary efficacy, defined as anti-HBs response ≥ 10 IU/l, was evaluated at week 28 in both study arms. RESULTS: A subset of 48 patients non-responsive to HBV vaccination was selected, from a cohort of patients at our institution, who underwent HBV vaccination unsuccessfully either in a previous RCT or through standard care. The anti-HBs ≥ 10 IU/l response rate at week 28 in the Fendrix® arm and the Engerix® arm were 85.7% and 65.0%, respectively (p = 0.09). There was no significant difference between the two used vaccine types in the anti-HBs levels reached. In our institution, the overall response rate after initial standard-dose vaccination schedule and double-dose revaccination in our cohort was 75%. In this study, combining the effects of Fendrix and Engerix resulted in a 75% response rate in the 25% remaining non-responders on initial and double-dose revaccination series. This yielded an absolute 19% increase and an overall response to HBV vaccination in HIV-infected patients of around 94% in our cohort. CONCLUSION: These results together, suggest that continuing HBV vaccination in non-responders to a first course of single-dose vaccine and a double-dose revaccination scheme is worth the effort. No superiority of one of the investigated hepatitis B vaccines was shown in this cohort but an appropriate number of patients needed to achieve reliable answers was not achieved.

A longitudinal and cross-sectional study ofEpstein-Barr virus DNA load: a possible predictor of AIDS-related lymphoma in HIV-infected patients.

INTRODUCTION: HIV-infected patients are more than 100-fold greater at risk for developing malignant AIDS-related lymphoma (ARL) compared to the general population. Most ARLs are EBV related. The main purpose of this study was to investigate whether a high peak EBV DNA load in HIV-infected patients is predictive of ARL, including classical Hodgkin lymphoma. METHODS: From an ongoing prospective HIV positive cohort study, we conducted a case-control study between 2004 and 2016 among patients from whom at least one EBV DNA load in serum or plasma was available. We compared peak EBV DNA load between patients with (49 cases) and without ARL (156 controls). RESULTS: The geometric mean of the peak EBV DNA load measured before diagnosis of malignant lymphoma was 52,565 IU/mL in EBER-positive lymphoma patients vs. 127 IU/mL in controls (p < .001). Patients with EBV DNA loads >100,000 IU/mL have an increased risk for diagnosis of malignant lymphoma compared to patients with EBV DNA loads ≤100,000 IU/mL (adjusted OR 12.53; 95%CI: 4.08; 38.42). In the longitudinal study, including 13 patients with at least three left-over plasma samples available for retesting, measurements of EBV-DNA during the preceding 12 months proved to be of poor value for predicting subsequent lymphoma diagnosis. CONCLUSIONS: A EBV DNA load >100,000 IU/mL can be useful in clinical setting to accelerate time to diagnosis and treatment. EBV-DNA loads in samples taken during the preceding year of ARL diagnosis showed to be of poor predictive value.

Virological and Social Outcomes of HIV-Infected Adolescents and Young Adults in The Netherlands Before and After Transition to Adult Care.

BACKGROUND: As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure. METHODS: We included 59 HIV-infected AYAs from the Netherlands who had entered into pediatric care and transitioned from pediatric to adult healthcare. We used HIV RNA load and cART data from the Dutch Stichting HIV Monitoring database (1996-2014), and collected social and treatment data from patients' medical records from all Dutch pediatric HIV treatment centers and 14 Dutch adult treatment centers involved. We evaluated risk factors for virological failure (VF) in a logistic regression model adjusted for repeated measurements. RESULTS: HIV VF occurred frequently during the study period (14%-36%). During the transition period (from 18 to 19 years of age) there was a significant increase in VF compared with the reference group of children aged 12-13 years (odds ratio, 4.26 [95% confidence interval, 1.12-16.28]; P = .03). Characteristics significantly associated with VF were low educational attainment and lack of autonomy regarding medication adherence at transition. CONCLUSIONS: HIV-infected AYAs are vulnerable to VF, especially during the transition period. Identification of HIV-infected adolescents at high risk for VF might help to improve treatment success in this group.

Risk factors in an HIV-infected population for refraining from specialist care.

BACKGROUND: To obtain maximal benefit of combination antiretroviral therapy (cART), HIV-infected patients should be retained in medical care. Missed clinical visits are independently associated with all-cause mortality among HIV-infected patients. Our objective was to identify risk factors and patient-reported reasons for nonattendance at outpatient clinic appointments. DESIGN AND METHODS: We conducted a cross-sectional case-control study among 447 HIV-infected patients attending the outpatient clinic between March and July 2014. Patients with missed appointments from January 2013 onwards were included as cases and compared to a random selection of same-day controls without missed appointments during the same period. Clinical and socio-demographic characteristics were collected from clinical records and an interviewer-administered questionnaire. Additionally, reasons for nonattendance and possible solutions for future better attendance were addressed in the questionnaire. Multivariable logistic regression analysis was used to determine independent risk factors for nonattendance. RESULTS: A total of 224 cases and 223 controls were included. Independent risk factors for nonattendance were: (i) age <30 years (odds ratio (OR) 7.2; 95% CI: 3.2-16.3 versus ≥50 years); (ii) African region of origin (OR 2.8; 95% CI: 1.5-5.0 versus Western origin); (iii) having children <12 years of age (OR 2.1; 95% CI: 1.1-4.1); (iv) history of drugs- or alcohol abuse (OR 4.4; 95% CI: 1.8-10.8); (v) no cART (OR 2.5; 95% CI: 1.1-5.3) or HIV-RNA >400 copies/ml while receiving cART (OR 3.5; 95% CI: 1.3-9.6). The main reason given for nonattendance was failure to remember the appointments (44%). Most patients would prefer to receive an appointment reminder by SMS (80% of the cases and 55% of the controls). CONCLUSION: Missing outpatient clinic appointments were associated with available clinical characteristics. Nonattendance may be prevented by sending routine SMS reminders prior to the next appointment.

Risk Factors for Sexual Transmission of Hepatitis C Virus Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men: A Case-Control Study.

Background. Since 2000, incidence of sexually acquired hepatitis C virus (HCV)-infection has increased among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). To date, few case-control and cohort studies evaluating HCV transmission risk factors were conducted in this population, and most of these studies were initially designed to study HIV-related risk behavior and characteristics. Methods. From 2009 onwards, HIV-infected MSM with acute HCV infection and controls (HIV-monoinfected MSM) were prospectively included in the MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study at 5 large HIV outpatient clinics in the Netherlands. Written questionnaires were administered, covering sociodemographics, bloodborne risk factors for HCV infection, sexual behavior, and drug use. Clinical data were acquired through linkage with databases from the Dutch HIV Monitoring Foundation. For this study, determinants of HCV acquisition collected at the inclusion visit were analyzed using logistic regression. Results. Two hundred thirteen HIV-infected MSM (82 MSM with acute HCV infection and 131 MSM without) were included with a median age of 45.7 years (interquartile range [IQR], 41.0-52.2). Receptive unprotected anal intercourse (adjusted odds ratio [aOR], 5.01; 95% confidence interval [CI], 1.63-15.4), sharing sex toys (aOR, 3.62; 95% CI, 1.04-12.5), unprotected fisting (aOR, 2.57; 95% CI, 1.02-6.44), injecting drugs (aOR, 15.62; 95% CI, 1.27-192.6), sharing straws when snorting drugs (aOR, 3.40; 95% CI, 1.39-8.32), lower CD4 cell count (aOR, 1.75 per cubic root; 95% CI, 1.19-2.58), and recent diagnosis of ulcerative sexually transmitted infection (aOR, 4.82; 95% CI, 1.60-14.53) had significant effects on HCV acquisition. Conclusions. In this study, both sexual behavior and biological factors appear to independently increase the risk of HCV acquisition among HIV-infected MSM.

Low mother-to-child-transmission rate of Hepatitis C virus in cART treated HIV-1 infected mothers.

BACKGROUND: Maternal transmission is the most common cause of HCV infection in children. HIV co-infection and high levels of plasma HCV-RNA have been associated with increased HCV transmission rates. OBJECTIVES: We assessed the vertical HCV transmission rate in the HIV-HCV co-infected group of pregnant women on cART. STUDY DESIGN: We conducted a retrospective study in a Dutch cohort of HIV-positive pregnant women and their children. We identified co-infected mothers. Results of the HCV tests of the children were obtained. RESULTS: All 21 women were on cART at the time of delivery. We analyzed data of the 24 live-born children at risk for mother-to-child transmission (MTCT) of HCV between 1996 and 2009. HIV-RNA was <500 copies/ml during 18/24 [75%] deliveries, the median CD4(+) cell count was 419 cells/µl (290-768). There was no transmission of HIV. The median plasma HCV-RNA in our cohort of 23 non-transmitting deliveries in 21 women was 3.5×10E5 viral eq/ml (IQR 9.6×104-1.5×106veq/mL). One of 24 live-born children was found to be infected with HCV genotype 1. At the time of delivery the maternal plasma HIV-RNA was <50 copies/ml, the CD4(+) cell count was 160 cells/µl and maternal plasma HCV-RNA was 4.6×10E6 veq/ml. This amounted to a prevalence of HCV-MTCT of 4%. CONCLUSION: In this well-defined cohort of HIV-HCV co-infected pregnant women, all treated with cART during pregnancy, a modest rate of vertical HCV transmission was observed.

Efficacy of tenofovir and efavirenz in combination with lamivudine or emtricitabine in antiretroviral-naive patients in Europe.

BACKGROUND: The combination of tenofovir and efavirenz with either lamivudine or emtricitabine (TELE) has proved to be highly effective in clinical trials for first-line treatment of HIV-1 infection. However, limited data are available on its efficacy in routine clinical practice. METHODS: A multicentre cohort study was performed in therapy-naive patients initiating ART with TELE before July 2009. Efficacy was studied using ITT (missing or switch = failure) and on-treatment (OT) analyses. Genotypic susceptibility scores (GSSs) were determined using the Stanford HIVdb algorithm. RESULTS: Efficacy analysis of 1608 patients showed virological suppression to <50 copies/mL at 48 weeks in 91.5% (OT) and 70.6% (ITT). Almost a quarter of all patients (22.9%) had discontinued TELE at week 48, mainly due to CNS toxicity. Virological failure within 48 weeks was rarely observed (3.3%, n = 53). In multilevel, multivariate analysis, infection with subtype B (P = 0.011), baseline CD4 count <200 cells/mm³ (P < 0.001), GSS <3 (P = 0.002) and use of lamivudine (P < 0.001) were associated with a higher risk of virological failure. After exclusion of patients using co-formulated compounds, virological failure was still more often observed with lamivudine. Following virological failure, three-quarters of patients switched to a PI-based regimen with GSS <3. After 1 year of second-line therapy, viral load was suppressed to <50 copies/mL in 73.5% (OT). CONCLUSIONS: In clinical practice, treatment failure on TELE regimens is relatively frequent due to toxicity. Virological failure is rare and more often observed with lamivudine than with emtricitabine. Following virological failure on TELE, PI-based second-line therapy was often successful despite GSS <3.

Hepatitis E prevalence among HIV infected patients with elevated liver enzymes in the Netherlands.

BACKGROUND: In recent years chronic hepatitis E virus (HEV) infections have been reported in immunosuppressed patients, including HIV-positive patients with low CD4 cell counts. Because of delayed anti-HEV seroconversion in patients with CD4 cell count<200 cells/ml it is difficult to draw firm conclusions on HEV-seroprevalence in a population of HIV positive patients. OBJECTIVES: To determine the HEV seroprevalence in a population of HIV infected patients. STUDY DESIGN: We retrospectively analysed the HEV prevalence in a population of 256 HIV infected patients with liver enzyme elevations (LEEs), using HEV specific antibody testing and HEV-RNA detection. RESULTS: Within this cohort we observed a HEV-seroprevalence of 11.7%, without any anti-HEV IgM positive or HEV-RNA positive cases. HEV seropositivity was equally prevalent among different CD4(+) cell count groups. CONCLUSION: Although HIV infected patients in the Netherlands are at risk of acquiring HEV, the number of acute infections is low and no chronic cases were found.

Deep sequencing does not reveal additional transmitted mutations in patients diagnosed with HIV-1 variants with single nucleoside reverse transcriptase inhibitor resistance mutations.

OBJECTIVES: The aim of the study was to gain more insight into the relationship between transmitted singletons found at HIV diagnosis by population sequencing and the possible presence of clinically relevant viral minorities containing additional resistance mutations. METHODS: We studied the viral quasispecies and therapy response in 10 individuals with transmitted single nucleoside reverse transcriptase inhibitor (NRTI)-related resistance mutations as detected by population sequencing. RESULTS: Ultra-deep pyrosequencing did not reveal additional drug-resistance mutations in nine of 10 patients. In these nine patients, no breakthrough with resistant viruses was observed despite the use of low genetic nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in the majority of patients. CONCLUSIONS: These data suggest that viral minority variants containing additional resistance mutations may be rare in patients with transmitted NRTI singletons in the Netherlands. Larger studies are required to confirm these findings and to determine the therapeutic consequences.

Risk factors and outcome of HIV-associated idiopathic noncirrhotic portal hypertension.

BACKGROUND: Idiopathic noncirrhotic portal hypertension (INCPH) has been reported increasingly in patients with HIV infection. AIM: To evaluate the number of nationwide diagnosed HIV-associated INCPH cases and to assess its clinical features, risk factors and outcome. METHODS: All HIV centres in the Netherlands were contacted and requested to notify INCPH cases diagnosed in their population. A case­control study was performed to identify the risk factors of INCPH. The cases were group-matched for duration of follow-up after HIV diagnosis to controls. Controls were selected from a database of HIV patients with negative screening for signs of portal hypertension on abdominal ultrasound. Univariate and multivariate conditional logistic regression analyses were performed. RESULTS: On 1st of July 2011, 18.085 individuals were infected with HIV in the Netherlands. Within this population, sixteen patients with clinically overt INCPH were identified. At the time of INCPH diagnosis, cases had a lower platelet count and a higher ALT level. In univariate and multivariate analyses, didanosine [OR: 1.9 (1.3­2.8)], concomitant didanosine and stavudine treatment [OR: 6.3 (2.1­19.1)] and concomitant didanosine and tenofovir treatment [OR: 5.1 (1.2­22.6)] were independently associated INCPH. During follow-up, 4 patients died [malignancy (n = 3), liver failure (n = 1)]. A significant decline in platelets was observed after didanosine discontinuation (P = 0.003). CONCLUSIONS: HIV-associated clinically relevant idiopathic noncirrhotic portal hypertension appears to be a rarely diagnosed disease. Long-term exposure to didanosine and short-term combination of didanosine and stavudine or tenofovir exposure are associated with idiopathic noncirrhotic portal hypertension. Mortality in HIV-associated idiopathic noncirrhotic portal hypertension is mainly related to HIV-associated disorders. Portal hypertension continues despite didanosine discontinuation

Use of highly active antiretroviral therapy is associated with lower prevalence of anal intraepithelial neoplastic lesions and lower prevalence of human papillomavirus in HIV-infected men who have sex with men.

BACKGROUND: The incidence of anal intraepithelial neoplasia (AIN) and anal cancer is increased in HIV-positive men who have sex with men (MSM). Persistent high-risk human papillomavirus (HPV) infection is an important etiologic agent. METHODS: In this study, a group of 250 HIV-positive MSM was included to determine the prevalence of AIN and to investigate the role of highly active antiretroviral therapy (HAART), high-risk HPV, and other risk factors possibly associated with this prevalence. RESULTS: Among patients included, 108 (43.2%) had lesions suspicious for AIN. Histologic analyses showed AIN 1 in 24 patients (22.2%), AIN 2 in 6 patients (5.6%), and AIN 3 in 10 patients (9.3%). In multivariable analyses, the use of HAART was associated with the absence of AIN (P = 0.045). In MSM without HAART, HPV infection was detected significantly more often compared with those who used HAART (P = 0.010). AIN was associated with HPV types 16 and 6. CONCLUSIONS: In this cross-sectional study in 250 HIV-positive MSM, the use of HAART was associated with lower prevalence of AIN and a significantly lower prevalence of HPV. This association between the prevalence of AIN and the absence of HAART may contribute to the current debate on when to start HAART in HIV-infected individuals.

Baseline lipid levels rather than the presence of reported body shape changes determine the degree of improvement in lipid levels after switching to atazanavir.

PURPOSE: To study factors influencing lipid changes after switching to atazanavir (ATV) and the effectiveness of ATV in maintaining virus suppression. METHODS: Retrospective cohort study in patients with viral suppression, comparing patients switching to ATV with those continuing combination antiretroviral therapy (cART). Outcome measures were 48-week total (TC), high-density (HDL) and low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) changes, stratified for dyslipidemia and lipodystrophy and virological failure (time to first of two consecutive detectable HIV RNA). RESULTS: 225 patients switched to ATV (193 [85.8%] RTV boosted), and 3120 continued cART. In patients with baseline TC >6.2 mmol/L, those switching had greater mean (95% CI) TC decreases compared to those continuing cART (-1.26 [-1.63 to -0.89] and -0.54 [-0.64 to -0.44] mmol/L, p = .002). Likewise greater TG changes were observed in patients with high (>2.3 mmol/L) baseline TG (-1.44 [-2.05 to -0.83] and -0.54 [-0.70 to -0.38] mmol/L, p = .002). Effects were seen irrespective of presence of lipodystrophy. Patients switching to ATV had virological failure more often (17/224 [7.8%]) than those continuing cART (73/3100 [2.4%], p < .0001). CONCLUSIONS: Patients with virological suppression, including those with lipodystrophy, may benefit from switching to ATV with lipid profile improvement, especially if baseline lipid levels are high. This should be balanced against a possible higher virological failure risk.

Plasma HCV-RNA decline in the first 48 h identifies hepatitis C virus mono-infected but not HCV/HIV-coinfected patients with an undetectable HCV viral load at week 4 of peginterferon-alfa-2a/ribavirin therapy.

During peginterferon-alfa-2a/ribavirin therapy, plasma hepatitis C virus (HCV)-RNA decreases with a rapid first phase and a slower second phase. We compared the viral load decrease and slope in the first 48 h in patients with a rapid viral response (RVR, i.e. HCV-RNA < 50 IU/mL at week 4) with patients not achieving an RVR. From 23 HCV-infected (14 mono-infected and nine HCV/HIV-coinfected) genotype 1 or 4 positive peginterferon-alfa-2a/ribavirin-treated patients, plasma HCV-RNA was determined at baseline, 48 h, weeks 1, 2, 4, 8, 12, 48 and 72. The HCV viral load decrease (Delta0-48), the slope (lambda(1)) and the efficiency factor (epsilon) were determined in the first 48 h after the start of therapy. Five (36%) HCV mono-infected patients and three (33%) HIV/HCV-coinfected patients achieved an RVR whereas six (43%) HCV mono-infected patients and five (56%) HIV/HCV-coinfected patients reached a sustained viral response (SVR). In contrast to HIV/HCV-coinfected patients, five HCV mono-infected patients with an RVR showed both a larger Delta0-48 and steeper lambda(1) (-1.77log(10) IU/mL +/- 0.66 and -2.04/day +/- 0.76) compared to nine non-RVR patients (-0.66log(10) IU/mL +/- 0.39; P = 0.019 and -0.76/day +/- 0.41; P = 0.019). When divided by SVR, a greater Delta0-48 and steeper lambda(1) were also seen in both HCV mono-infected and HIV/HCV-coinfected patients. Thus, in the first 48 h after the start of therapy, HCV mono-infected patients with an RVR have a larger viral load decrease, steeper viral slope and a higher efficiency factor as compared with non-RVR patients.

Steady-state nevirapine plasma concentrations are influenced by pregnancy.

OBJECTIVES: Optimal plasma concentrations of antiretroviral drugs are required during pregnancy to treat maternal HIV infection and prevent mother-to-child transmission. We investigated the effect of pregnancy on nevirapine (NVP) plasma concentrations. METHODS: We included all HIV-1-infected women for whom NVP plasma concentrations were available as part of routine patient care at two university hospitals. Plasma NVP concentrations were compared for pregnant (n=45) and non-pregnant (n=152) women. Univariate and multivariate linear regression analyses were used to identify and adjust for other confounding factors associated with NVP plasma concentrations. For pregnant women who had a plasma NVP concentration available both during and outside pregnancy, a paired analysis was performed. RESULTS: Steady-state NVP plasma concentrations were lower in pregnant women: 5.2 mg/L (interquartile range 3.9-6.8) vs. 5.8 mg/L (4.3-7.7) (P=0.08). After adjusting for confounders, both pregnancy (regression coefficient=-0.90 mg/L, P=0.046) and African descent (regression coefficient=+1.13 mg/L, P=0.005) influenced NVP concentrations significantly. The paired analysis showed mean concentrations of 4.8 mg/L during pregnancy and 5.8 mg/L outside pregnancy (paired t-test, P=0.073). CONCLUSIONS: Pregnancy has a moderate but significant lowering effect on NVP plasma concentrations. Being of African descent compensates for the lowering effect of pregnancy on NVP concentrations.

The AmRo study: pregnancy outcome in HIV-1-infected women under effective highly active antiretroviral therapy and a policy of vaginal delivery.

OBJECTIVE: To explore pregnancy outcome in HIV-1-positive and HIV-negative women, and mother-to-child transmission (MTCT) according to mode of delivery under effective highly active antiretroviral therapy (HAART). DESIGN: Cohort of 143 pregnant HIV-1-infected women including a matched case-control study in a 2:1 ratio of controls to cases (n=98). SETTING: Academic Medical Center in Amsterdam and Erasmus Medical Center in Rotterdam, the Netherlands. POPULATION: Consecutive referred HIV-1 infected pregnant women treated with HAART and matched control not infected pregnant women. MAIN OUTCOME MEASURES: MTCT, preterm delivery, low birthweight, pre-eclampsia. RESULTS: MTCT was 0% (95% CI 0-2.1%). Seventy-eight percent of HIV-1-infected women commenced and 62% completed vaginal delivery. The calculated number of caesarean sections needed to prevent a single MTCT was 131 or more. Preterm delivery rates were 18% (95% CI 11-27) in women infected with HIV-1 and 9% (95% CI 5-13) in controls (P=0.03). HAART used at <13 weeks of gestation was associated with a 44% preterm delivery rate compared with 21% when HAART was started at or after 13 weeks and 14% in controls. (Very) low birthweight and incidence of pre-eclampsia were not different between HIV-1 and controls. CONCLUSIONS: We have not demonstrated any MTCT after vaginal delivery in women effectively treated by HAART. The HAART-associated increase in preterm delivery rate is mainly seen after first trimester HAART use.

Wild type and YMDD variant of hepatitis B virus: no difference in viral kinetics on lamivudine/tenofovir therapy in HIV-HBV co-infected patients.

Prolonged lamivudine therapy has been identified as the major risk for the development of resistance in HBV, with rates of 90% after 4 years of treatment. Tenofovir disoproxil fumarate showed activity against both wild type and lamivudine resistant HBV in HIV-HBV co-infected patients. In order to compare the efficacy of lamivudine/tenofovir treatment we investigated detailed HBV kinetics in 13 HIV-HBV co-infected patients with either wild type HBV or lamivudine resistant HBV. The viral strains in both patient groups showed a biphasic viral decline pattern. Only in the first phase of viral decay, which reflects the clearance rate of the free virus from plasma, there was a statistically significant response in favor of the wild type group. After the first phase we observed a similar viral decline till 24 weeks of both groups. This is reassuring for many pretreated co-infected patients harbouring mutant viruses.

[Anorectal malignancies and dysplasia in HIV-positive men who have sex with men]. / Anuscarcinoom en voorstadia hiervan bij HIV-positieve mannen die seks hebben met mannen.

Since the HIV epidemic, the incidence ofanorectal (pre)malignancies in men who have sex with men (MSM) is increasing. The incidence is likely to increase further in the coming years, given that HIV-positive MSM are living longer thanks to powerful antiretroviral treatment. Persistent human papillomavirus (HPV) infection is a major risk factor for the development of anal (pre)malignancies. Less is known about the natural history of anal intraepithelial neoplasia (AIN). Screening in HIV-positive and HIV-negative MSM for anorectal malignancies or dysplasia is cost-effective if the incidence is sufficiently high. Treatment options range from watchful waiting for asymptomatic grade-1 AIN to excision or radio(chemo)therapy for anorectal carcinoma. HPV vaccines are in development. Especially in HIV-positive MSM with anorectal complaints or genital warts in their medical history, one should consider these malignancies.

CCR5, GPR15, and CXCR6 are major coreceptors of human immunodeficiency virus type 2 variants isolated from individuals with and without plasma viremia.

Human immunodeficiency virus type 2 (HIV-2) is generally considered capable of using a broad range of coreceptors. Since HIV-2 variants from individuals with nonprogressive infection were not studied previously, the possibility that broad coreceptor usage is a property of variants associated with progressive infection could not be excluded. To test this, we determined the coreceptor usage of 43 HIV-2 variants isolated from six long-term-infected individuals with undetectable plasma viremia. Using GHOST indicator cells, we showed for the first time that the only coreceptors efficiently used by low-pathogenic HIV-2 variants are CCR5, GPR15 (BOB), and CXCR6 (BONZO). Surprisingly, control HIV-2 variants (n = 45) isolated from seven viremic individuals also mainly used these three coreceptors, whereas use of CCR1, CCR2b, or CCR3 was rare. Nearly a quarter of all HIV-2 variants tested could infect the parental GHOST cells, which could be partially explained by CXCR4 usage. Use of CXCR4 was observed only for HIV-2 variants from viremic individuals. Thirty-eight variants from aviremic and viremic HIV-2-infected individuals were additionally tested in U87 cells. All except one were capable of infecting the parental U87 cells, often with high efficiency. When virus production in parental cells was regarded as background in the coreceptor-transduced cell lines, the results in U87 cells were largely in agreement with the findings in GHOST cells. HIV-2 isolates from aviremic individuals commonly use as coreceptors CCR5, GPR15, and CXCR6, as well as an unidentified receptor expressed by U87 cells. Broad coreceptor usage, therefore, does not appear to be associated with pathogenicity of HIV-2.

[Sexual transmission of hepatitis C in homosexual men]. / Seksuele overdracht van hepatitis C bij homoseksuele mannen.

An acute hepatitis C infection was diagnosed in three HIV-positive gay men, aged 43, 48 and 30 years, respectively. In all three, unprotected sexual intercourse and fisting was a universal risk factor for the infection. They all denied having used drugs intravenously, which is the most common risk factor. The third man had a documented proctitis (lymphogranuloma venereum) at the time when the HCV transmission must have taken place. No serious complications occurred during the acute HCV infection. Because the infection did not resolve spontaneously after a few months, all three men were treated with pegylated interferon and ribavirin. Recently, the number of cases of acute HCV infection has been seen to increase in The Netherlands. This may be due primarily to an increase in unprotected sexual intercourse and fisting. This hypothesis is supported by a documented increased prevalence of sexually transmissible diseases among gay men in The Netherlands. As acute infections may turn into chronic infections, treatment of an acute infection should be considered in order to prevent the chronic disease.

[Highly active antiretroviral therapy (HAART) in HIV-positive pregnant women in the Netherlands, 1997-2003: safe, effective and with few side effects]. / Krachtige antiretrovirale therapie (HAART) bij HIV-positieve zwangeren in Nederland, 1997-2003: veilig, effectief en met weinig bijwerkingen.

OBJECTIVE: To assess the side effects, safety and efficacy of highly active antiretroviral therapy (HAART) in a cohort of HIV-infected pregnant women in the Netherlands. DESIGN: Retrospective. METHOD: Data were collected from the medical records of HIV-infected pregnant women who received HAART during pregnancy in the period 1 January 1997-1 June 2003 at 14 HIV-specialized centres in the Netherlands. The inclusion criteria were at least a triple drug regimen and birth at 20 or more weeks of gestation. Information was collected about patient characteristics, HAART prescribed, side effects, viral load response, mode of delivery and HIV-status of the neonate. RESULTS: A total of 267/413 women satisfied the inclusion criteria. Most women (n = 199) had not previously received anti-retroviral therapy and started HAART between weeks 21 and 28 of the pregnancy. The two most frequently used regimens contained nelfinavir (57%) or nevirapine (31%). Gastrointestinal side effects were more frequently observed in the nelfinavir group, while rash and hepatotoxicity were more frequently reported in the nevirapine group. Efficacy and pregnancy outcome were similar in both groups. Two infants (0.7%) were HIV-infected. CONCLUSION: HAART regimens containing nelfinavir or nevirapine in HIV-infected pregnant women were safe, effective and well tolerated.