Clinical characteristics of women with HIV in the RESPOND cohort: A descriptive analysis and comparison to men.

BACKGROUND: Women with HIV are globally underrepresented in clinical research. Existing studies often focus on reproductive outcomes, seldom focus on older women, and are often underpowered to assess sex/gender differences. We describe CD4, HIV viral load (VL), clinical characteristics, comorbidity burden, and use of antiretroviral therapy (ART) among women with HIV in the RESPOND study and compare them with those of the men in RESPOND. METHODS: RESPOND is a prospective, multi-cohort collaboration including over 34 000 people with HIV from across Europe and Australia. Demographic and clinical characteristics, including CD4/VL, comorbidity burden, and ART are presented at baseline, defined as the latter of 1 January 2012 or enrolment into the local cohort, stratified by age and sex/gender. We further stratify men by reported mode of HIV acquisition, men who have sex with men (MSM) and non-MSM. RESULTS: Women account for 26.0% (n = 9019) of the cohort, with a median age of 42.2 years (interquartile range [IQR] 34.7-49.1). The majority (59.3%) of women were white, followed by 30.3% Black. Most women (75.8%) had acquired HIV heterosexually and 15.9% via injecting drug use. Nearly half (44.8%) were receiving a boosted protease inhibitor, 31.4% a non-nucleoside reverse transcriptase inhibitor, and 7.8% an integrase strand transfer inhibitor. The baseline year was 2012 for 73.2% of women and >2019 for 4.2%. Median CD4 was 523 (IQR 350-722) cells/µl, and 73.6% of women had a VL <200 copies/mL. Among the ART-naïve population, women were more likely than MSM but less likely than non-MSM (p < 0.001) to have CD4 <200 cells/µL and less likely than both MSM and non-MSM (p < 0.001) to have VL ≥100 000 copies/mL. Women were also more likely to be free of comorbidity than were both MSM and non-MSM (p < 0.0001). CONCLUSION: RESPOND women are diverse in age, ethnicity/race, CD4/VL, and comorbidity burden, with important differences relative to men. This work highlights the importance of stratification by sex/gender for future research that may help improve screening and management guidelines specifically for women with HIV.

Guidelines and practice of breastfeeding in women living with HIV-Results from the European INSURE survey.

INTRODUCTION: Antiretroviral therapy (ART) is integral to HIV prevention, including averting vertical transmission. The World Health Organization (WHO) recommends ART and breastfeeding for all women living with HIV for at least 12 months post-partum [1, 2]. Much of the data on HIV transmission through breastfeeding comes from low-resource settings, with a paucity of data on breastfeeding-related HIV transmission in women living with HIV in other settings. Women Against Viruses in Europe (WAVE), part of the European AIDS Clinical Society (EACS), aims to improve the standard of care for women living with HIV and sought to gain an understanding of breastfeeding guidelines and practice in women living with HIV across Europe. METHODS: A steering group convened by WAVE developed a survey to collate information on breastfeeding trends, practice, and guideline recommendations for women living with HIV in Europe and to establish interest in becoming involved in a collaborative breastfeeding network. The survey was disseminated to 31 countries in March 2022. RESULTS: In total, 25 eligible responses were received: 23/25 (92%) countries have HIV and pregnancy guidelines; 23/23 (100%) guidelines refer specifically to breastfeeding; 12/23 (52%) recommend against breastfeeding; 11/23 (48%) offer an option if certain criteria are met; 12/25 (48%) reported that the number of women living with HIV who breastfeed is increasing; 24/25 (96%) respondents were interested in joining a network on breastfeeding in women living with HIV. CONCLUSIONS: Recommendations vary, and nearly half of the guidelines recommend against breastfeeding. Many countries report an increase in breastfeeding. WAVE will establish a collaborative network to bridge data gaps, conduct research, and improve support for women living with HIV who choose to breastfeed.

Antiretroviral treatment outcomes among late HIV presenters initiating treatment with integrase inhibitors or protease inhibitors.

OBJECTIVES: The aim of the study was to investigate the efficacy and safety of first-line antiretroviral therapy (ART) with integrase inhibitor (INI) or protease inhibitor (PI)-based regimens in patients with low CD4 cell counts and/or an AIDS-defining disease. METHODS: We conducted a retrospective, multicentre analysis to investigate discontinuation proportions and virological response in patients with CD4 cell counts < 200 cells/µL and/or AIDS-defining disease when starting first-line ART. Proportions of those discontinuing ART were compared using univariate analysis. Virological response was analysed using the Food & Drug Administration (FDA) snapshot analysis (HIV-1 RNA < 50 HIV-1 RNA copies/mL at week 48). RESULTS: Two hundred and eighteen late presenters were included in the study: 13.8% were women and 23.8% were of non-European ethnicity, and the mean baseline CD4 count was 91 cells/µL (standard deviation 112 cells/µL). A total of 131 late presenters started on INI- and 87 on PI-based treatment. It was found that 86.1% of patients treated with INIs and 81.1% of patients treated with PIs had a viral load < 50 copies/mL at week 48; proportions of discontinuation because of adverse events were 6.1% in the INI group and 11.5% in the PI group. No significant differences in discontinuation proportions were observed at week 12 or 48 between INI- and PI-based regimens (P = 0.76 and 0.52, respectively). Virological response was equally good in those receiving INIs and those receiving PIs (86.1% vs. 81.1%, respectively; P = 0.36). CONCLUSIONS: In a European cohort of late presenters starting first-line INI or PI-based ART regimens, there were no significant differences in discontinuation proportions or virological response at week 48.

Severe underquantification of HIV-1 group O isolates by major commercial PCR-based assays.

HIV-1 diversity poses major challenges to viral load assays because genetic polymorphisms can impede nucleic acid detection. In addition to the on-going viral diversification within the HIV-1 group M pandemic, HIV-1 genetic diversity is further increased by non-group M infections, such as HIV-1 groups O (HIV-1-O), N and P. We here conducted a systematic evaluation of commercially available PCR assays to detect HIV-1-O isolates. We collected 25 primary HIV-1-O isolates covering all genetic clusters within HIV-1-O. Subsequently, this panel of isolates was tested on eight commercially available quantitative and five qualitative HIV-1 PCR-based assays in serial dilutions. Sequence analyses were performed for severe cases of underquantification or lack of detection. We observed differences between the assays in quantification that depended on the HIV-1-O isolate's subgroup. All three tested HIV-1-O subgroup IV isolates were underquantified by the Roche CAP/CTM >800-fold compared to the Abbott RealTime assay. In contrast, the latter assay underquantified several subgroup I isolates >200-fold. Notably, the Xpert HIV-1 Viral Load test from Cepheid failed to detect two of the HIV-1-O isolates, whereas the Roche Cobas 8800 assay readily detected all isolates. Comparative sequence analyses identified polymorphisms in the HIV-1-O long-terminal repeat and integrase genes that likely underlie inadequate nucleic acid amplification. Potential viral load underquantification should be considered in therapeutic monitoring of HIV-1-O-infected patients. Pre-clinical assessments of HIV-1 diagnostic assays could be harmonized by establishing improved and internationally standardized panels of HIV-1 isolates that cover the dynamic diversity of circulating HIV-1 strains.

Sex and Gender Differences in Rilpivirine based ART - Data from the HIVCENTER Frankfurt.

OBJECTIVE: While Rilpivirine has shown high overall response rates in treatment-naïve patients without sex and gender specific differences in clinical trials, Sex and gender specific data in treatment experienced patients receiving rilpivirine are still limited. We conducted a 48 week efficacy and safety analysis in naïve and treatment experienced men and women using retrospective data from the HIVCENTER Frankfurt. MATERIALS AND METHODS: In this retrospective observational study data of all patients who received a rilpivirine based regimen at the HIVCENTER between March 2011 and December 2015 were analyzed. Primary endpoint was the proportion of patients with any discontinuation until week 48. Virologic response rates (FDA snapshot analysis; HIV-1 RNA <50 copies/mL) were assessed at week 48. RESULTS: 194 patients (34% female) were included in the analysis. 74% were treatment-experienced and 26% naïve, respectively. Discontinuations were observed in 31 (15.9%) patients. Regarding sex differences, the proportion of discontinuations was significantly higher in women than in men (24.2% vs. 11.7%; p=0.024; ODDS-Ratio = 2.41; CI 1.12 - 5.18). Virologic failure occurred in 8 PLWHIV (4.1%). CONCLUSION: While virologic overall response rates to rilpivirine based ART were high for both treatment-experienced and -naïve patients the proportion of discontinuations was significantly higher in women (24.2% vs. 11.7%; p = 0.024; ODDS-Ratio = 2.41; CI 1.12 - 5.18). Although the total number of patients with virologic failure was low (4.1%), the higher rate of ART discontinuations in female patients receiving RPV require close monitoring in the first months of treatment addressing special needs of women living with HIV.

Similar long-term efficacy of dual therapy containing raltegravir and a boosted protease inhibitor versus standard triple therapies in pretreated HIV-1-infected patients in a retrospective, real-life cohort of 14 years.

OBJECTIVES: Raltegravir is used in many antiretroviral combinations, but its use in treatment-experienced patients without knowledge of baseline resistance is discussed controversially as a number of comparative studies have shown a higher rate of virological failure. However, it has been used frequently for the management of treatment failure, as it was the first integrase inhibitor to become available, and thus offered new options for patients with multiple resistance. The strategic use of raltegravir in this setting is examined in this study. METHODS: In order to examine the efficacy of raltegravir in second and later lines of antiretroviral combinations, data for 740 patients from three clinical cohorts were analysed with a focus on the combinations that were used. These were stratified into the combination of two nonnucleoside reverse transcriptase inhibitors and raltegravir (2NRTIs + RAL), the combination of a boosted protease inhibitor and raltegravir (bPI + RAL), and other raltegravir-containing combinations. RESULTS: The overall rate of virological suppression to < 50 HIV-1 RNA copies/mL was 69.5%. Although the baseline rate of virological suppression was higher for 2NRTIs + RAL than for the other strata, the outcomes were similar for all three groups at weeks 24, 48, 72 and 96. CONCLUSIONS: These data indicate that, in a real-life setting, raltegravir can be used with a high virological success rate in treatment-experienced patients, and that the different combinations analysed (2NRTIs + RAL, bPI + RAL and others) show comparable rates of virological suppression.

Efficacy of raltegravir-containing regimens in antiretroviral-naïve and -experienced individuals in routine clinical practice.

Raltegravir is one of the standard antiretroviral therapy (ART) options in treatment-experienced and -naïve patients. However, efficacy data from clinical practice are scarce. Therefore, the efficacy of raltegravir-containing ART in clinical practice was investigated retrospectively. In all, 295 treatment-naïve and -experienced patients were analysed using two different cut-offs for virological failure (200 or 50 copies/ml). The response at week 24 and onwards was evaluated as a 'time to loss of virological response' analysis and estimated as a survival function. Additionally, dual therapy regimens (raltegravir plus boosted protease inhibitor) were compared to standard combinations in experienced patients performing a snapshot analysis at weeks 24 and 48, as well as a time to loss of virological response analysis. A total of 86.2% of the 64 treatment-naïve patients maintained virological suppression using a cut-off of 200 copies/ml (c/ml), while 67.7% maintained virological suppression with a 50 copies/ml cut-off from week 24 until the end of observation. Among the 231 treatment-experienced patients, 84.8% maintained virological suppression from week 24 onwards using a cut-off of 200 copies/ml; and 71.0% using 50 copies/ml, respectively. In the subgroup snapshot analysis at week 24, 98.3% (86.7% using a cut-off of 50 copies/ml) and at week 48, 93.3% (80.0%) of patients responded to dual therapy. Patients who were receiving a standard background therapy responded in 88.3% (81.3%) at week 24 and in 86.0% (80.7%) at week 48. Differences were not significant. This study shows again the overall long-term efficacy of raltegravir-based ART and furthermore gives reference for a comparable efficacy of dual and standard nucleos(t)ide reverse transcriptase inhibitor-backbone regimens in experienced patients on raltegravir over a period of 48 weeks in a real-life cohort where patients with severe comorbidities were included.

Incidence of CMV co-infection in HIV-positive women and their neonates in a tertiary referral centre: a cohort study.

Co-infection with CMV in HIV-positive pregnant women is associated with perinatal mother-to-child transmission (MTCT) of both viruses. This retrospective study reports on the incidence of maternal and neonatal CMV (presence of anti-CMV IgG and IgM, CMV DNA PCR and/or CMV virus isolation) in high-risk pregnancies due to maternal HIV infection, MTCT of HIV and/or CMV. One hundred and eleven maternal samples and 75 matched neonatal samples were available for HIV and subsequent CMV testing. In this cohort of HIV-positive pregnant women, 96 (86.5 %) serum samples were anti-CMV IgG positive. In nine (9.4 %) of these, anti-CMV IgM was detected, and in none of them a maternal primary CMV infection was suspected. Fifty-seven (51.8 %) maternal serum samples were tested retrospectively by CMV DNA PCR; one sample was positive (0.9 %). All matched neonates were tested for HIV by PCR in the first month of life; HIV transmission was detected in one case. In 74 (67.2 %) of neonates, CMV testing was performed. Sixty-six of these serum samples were tested retrospectively by CMV DNA PCR. Two newborns (2.7 %) showed laboratory markers for CMV infection (one by detection of CMV DNA in plasma, and one by isolation of CMV from a urine sample). In the follow-up, neither of these two showed clinical signs for active CMV disease. We discussed these findings in the light of the national official guidelines. All CMV transmissions occurred due to maternal reinfection or endogenous reactivation. This suggests the success of highly active antiretroviral therapy in preventing MTCT of HIV and CMV disease and highlights the importance of adequate care and follow-up.

Pregnancy complications in HIV-positive women: 11-year data from the Frankfurt HIV Cohort.

OBJECTIVES: The aim of the study was to assess pregnancy complications in HIV-positive women and changes in the rates of such complications over 11 years in the Frankfurt HIV Cohort. METHODS: There were 330 pregnancies in HIV-positive women between 1 January 2002 and 31 December 2012. The rate of pregnancy-related complications, such as gestational diabetes mellitus (GDM), pre-eclampsia and preterm delivery, the mode of delivery and obstetric history were analysed. Maternal and neonatal morbidity/mortality as well as HIV mother-to-child transmission (MTCT) were evaluated. RESULTS: In our cohort, GDM was diagnosed in 38 of 330 women (11.4%). Five women (1.5%) developed pre-eclamspia or hypertension. In 16 women (4.8%), premature rupture of membranes (PROM) occurred and 46 women (13.7%) were admitted with preterm contractions. The preterm delivery rate was 36.5% (n = 122), and 26.9% of deliveries (n = 90) were between 34+0 and 36+6 weeks of gestation. Over the observation period, the percentage of women with undetectable HIV viral load (VL) increased significantly (P < 0.001), from 26.1% to 75%, leading to obstetric changes, including an increase in the rate of vaginal deliveries (P < 0.001), from no vaginal births to 50%. The preterm delivery rate decreased significantly (P < 0.001), from 79.2% to 8.3%. There were no significant changes in the rate of GDM, pre-eclampsia, PROM or preterm contractions. CONCLUSIONS: In the 11 years of our analysis, there was a significant reduction in the rate of preterm deliveries and an increase in the vaginal delivery rate, possibly reflecting changes in treatment policies in the same period and the availability of more effective antiretroviral therapy options. The rates of complications such as GDM, pre-eclampsia, preterm contractions, PROM and postnatal complications were stable over the 11 years, but were still increased compared with the general population.

Prenatal ultrasound screening for fetal anomalies and outcomes in high-risk pregnancies due to maternal HIV infection: a retrospective study.

OBJECTIVE: To assess the prevalence of prenatal screening and of adverse outcome in high-risk pregnancies due to maternal HIV infection. STUDY DESIGN: The prevalence of prenatal screening in 330 pregnancies of HIV-positive women attending the department for prenatal screening and/or during labour between January 1, 2002 and December 31, 2012, was recorded. Screening results were compared with the postnatal outcome and maternal morbidity, and mother-to-child transmission (MTCT) was evaluated. RESULTS: One hundred of 330 women (30.5%) had an early anomaly scan, 252 (74.5%) had a detailed scan at 20-22 weeks, 18 (5.5%) had a detailed scan prior to birth, and three (0.9%) had an amniocentesis. In seven cases (2.12%), a fetal anomaly was detected prenatally and confirmed postnatally, while in eight (2.42%) an anomaly was only detected postnatally, even though a prenatal scan was performed. There were no anomalies in the unscreened group. MTCT occurred in three cases (0.9%) and seven fetal and neonatal deaths (2.1%) were reported. CONCLUSION: The overall prevalence of prenatal ultrasound screening in our cohort is 74.5%, but often the opportunity for prenatal ultrasonography in the first trimester is missed. In general, the aim should be to offer prenatal ultrasonography in the first trimester in all pregnancies. This allows early reassurance or if fetal disease is suspected, further steps can be taken.

Acute kidney injury caused by tenofovir disoproxil fumarate and diclofenac co-administration.

OBJECTIVES: The renal elimination of tenofovir (TFV) may be subject to renal drug-drug interactions that may increase the risk of kidney injury. Case reports indicated that diclofenac might increase TFV-associated nephrotoxicity via a drug-drug interaction, leading to an increased intracellular TFV concentration in proximal tubular cells. METHODS: A retrospective analysis of data for all patients from the Frankfurt HIV Cohort (FHC) who had diclofenac prescriptions between January 2008 and June 2012 was carried out. RESULTS: Among 89 patients with diclofenac use, 61 patients (68.5%) were treated with tenofovir disoproxil fumarate (TDF) and 28 patients (31.5%) were treated with TDF-sparing combination antiretroviral therapy (cART). Thirteen patients (14.6%) developed acute kidney injury (AKI) shortly after initiating diclofenac treatment. AKI occurred exclusively in TDF-treated patients, although all had previously stable renal function. All cases were accompanied by new onset of at least two parameters indicating proximal tubular damage, such as normoglycaemic-glucosuria and hypophosphataemia. TFV-associated nephrotoxicity was demonstrated by renal biopsy in four cases. Additionally, 11.5% of patients on TDF treatment developed new-onset proximal tubular damage, while having a preserved glomerular filtration rate. In contrast, diclofenac did not affect renal function in patients with TDF-sparing cART, as only one case of isolated hypophataemia was observed in these patients. In univariate analysis, risk factors for AKI were TDF-containing cART (P = 0.0076) and pre-existing hypophosphataemia (P = 0.0086). CONCLUSIONS: Drug-drug interaction caused by diclofenac could exacerbate TFV-associated nephrotoxicity. Diclofenac should be used with caution in patients on TDF therapy, especially in those with hypophosphataemia. Our findings need to be confirmed in larger studies.

End-stage renal disease and dialysis in HIV-positive patients: observations from a long-term cohort study with a follow-up of 22 years.

OBJECTIVES: Renal disease is a common and serious complication in HIV-infected patients. METHODS: A retrospective cohort analysis for the period 1989-2010 was carried out to determine the prevalence, incidence and risk factors for end-stage renal disease (ESRD). ESRD was defined as initiation of renal replacement therapy. Three time periods were defined: 1989-1996 [pre-highly active antiretroviral therapy (HAART)], 1997-2003 (early HAART) and 2004-2010 (late HAART). RESULTS: Data for 9198 patients [78.2% male; 88.9% Caucasian; cumulative observation time 68 084 patient-years (PY)] were analysed. ESRD was newly diagnosed in 35 patients (0.38%). Risk factors for ESRD were Black ethnicity [relative risk (RR) 5.1; 95% confidence interval (CI) 2.3-10.3; P < 0.0001], injecting drug use (IDU) (RR 2.3; 95% CI 1.1-4.6; P = 0.02) and hepatitis C virus (HCV) coinfection (RR 2.2; 95% CI 1.1-4.2; P = 0.03). The incidence of ESRD decreased in Black patients over the three time periods [from 788.8 to 130.5 and 164.1 per 100 000 PY of follow-up (PYFU), respectively], but increased in Caucasian patients (from 29.9 to 41.0 and 43.4 per 100 000 PYFU, respectively). The prevalence of ESRD increased over time and reached 1.9 per 1000 patients in 2010. Mortality for patients with ESRD decreased nonsignificantly from period 1 to 2 (RR 0.72; P = 0.52), but significantly from period 1 to 3 (RR 0.24; P = 0.006), whereas for patients without ESRD mortality decreased significantly for all comparisons. ESRD was associated with a high overall mortality (RR 9.9; 95% CI 6.3-14.5; P < 0.0001). CONCLUSION: As a result of longer survival, the prevalence of ESRD is increasing but remains associated with a high mortality. The incidence of ESRD declined in Black but not in Caucasian patients. IDU and HCV were identified as additional risk factors for the development of ESRD.

Tuberculosis skin test, but not interferon-γ-releasing assays is affected by BCG vaccination in HIV patients.

OBJECTIVE: Of this study was to compare the results of tuberculin skin test (TST) with two interferon-γ releasing-assays (IGRA) in a cohort of HIV positive patients, to analyze impact of prior Bacille-Calmette-Guérin (BCG)-vaccination. METHODS: Prospective cross sectional study, enrolling only asymptomatic adult HIV infected outpatients from a large German University hospital clinic. All participants were simultaneously tested for latent tuberculosis infection (LTBI) by QuantiFERON-TB Gold, T-SPOT.TB and TST. Only individuals with available definite results (positive/negative, indeterminates excluded) from all three test systems and recalling BCG-vaccination status by interview questionnaire were evaluated. RESULTS: From 286 study participants, 133 were evaluable; BCG-vaccination history was positive for 18 individuals, and negative for 115. The proportion of individuals with a positive TST was significantly higher for vaccinated (n = 6, 33.3%) than for unvaccinated individuals (n = 13, 11.3%, p = 0.013). There were no significant differences in the proportion of patients with CDC stage C, origin from a TB endemic country or in the CD4 count between the two groups. CONCLUSION: TST but not IGRAs interfered significantly with prior BCG vaccination in a cohort of HIV infected individuals from a low prevalence TB country. Therefore IGRA should preferentially be used for LTBI-testing in BCG-vaccinated adult HIV-patients.

[Prevention of nosocomial transmission of human immunodeficiency virus (HIV) from HIV-positive healthcare workers. Recommendations of the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V]. / Prävention der nosokomialen Übertragung von humanem Immunschwächevirus (HIV) durch HIV-positive Mitarbeiterinnen und Mitarbeiter im Gesundheitswesen. Empfehlungen der Deutschen Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) e.V. und der Gesellschaft für Virologie (GfV) e.V.

To the best of our knowledge, the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V. are the first in Europe to provide precise recommendations for the management of health care workers (HCWs) who are infected with human immunodeficiency virus (HIV). Requirements for HIV-infected HCWs need to be clearly defined. With a permanent viral burden of less than or equal to 50 copies/mL, HIV-positive HCWs are allowed to perform any surgery and any invasive procedure, as long as the infected HCW uses double-gloving, undergoes follow-up routinely by occupational medicine professionals, undergoes a quarterly examination of viral burden, and has a regular medical examination by a physician who has expertise in the management of HIV. Unrestricted professional activity is only possible with a strict compliance to take antiretroviral therapy and if the HIV-infected HCW strictly adheres to the recommended infection control procedures. Complete compliance with the recommendation almost certainly leads to no HIV transmission risk in patient care.

[Blood-borne infections and the pregnant health care worker. Risks and preventive measures]. / Blutübertragbare Infektionen und die schwangere Mitarbeiterin im Gesundheitswesen. Risiko und Präventionsmaßnahmen.

Due to the increasing proportion of women in health care, as well as changes in working conditions (implementation of safety devices, minimally invasive/endoscopic procedures) the question arises whether the applicable laws and regulations for the protection of working mothers are outdated and should be updated.Individual risk analysis, as well as the inclusion of the pregnant health care worker in the decision-making process with regard to continuation or modification of the work practice serves as a protection of the expectant mother and unborn child and allows a continuation of the occupational activities.

Efficacy, adherence and tolerability of once daily tenofovir DF-containing antiretroviral therapy in former injecting drug users with HIV-1 receiving opiate treatment: results of a 48-week open-label study.

OBJECTIVE: To assess efficacy, adherence and tolerability of once daily antiretroviral therapy containing tenofovir disoproxil fumarate (DF) 300 mg in HIV-1-infected former injecting drug users receiving opiate treatment (IVDU). METHODS: European, 48-week, open-label, single-arm, multicenter study. Patients were either antiretroviral therapy-naive, restarting therapy after treatment discontinuation without prior virological failure or switching from existing stable treatment. RESULTS: Sixty-seven patients were enrolled in the study and 41 patients completed treatment. In the primary analysis (intent-to-treat missing=failure) at week 48, 34% of patients (23/67; 95% CI: 23%-47%) had plasma HIV-1 RNA <50 copies/mL. Using an intent-to-treat missing=excluded approach, the week 48 proportion of patients with plasma HIV-1 RNA <50 copies/mL increased to 56% (23/41; 95% CI: 40%-72%). Mean (standard deviation) increase from baseline in CD4+ cell count at week 48 was 176 (242) cells/mm(3). Although self-reported adherence appeared high, there were high levels of missing data and adherence results should be treated with caution. No new safety issues were identified. CONCLUSIONS: Levels of missing data were high in this difficult-to-treat population, but potent antiretroviral suppression was achieved in a substantial proportion of HIV-infected IVDU-patients.

Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R.

OBJECTIVES: The reverse transcriptase (RT)-mutation K65R limits further therapeutic options and has been selected by unfavorable RT-combinations, e.g. tenofovir in combination with abacavir and/or didanosine. METHODS: We identified HIV-1 infected patients from a large treatment cohort who experienced virological failure (HIV-1 RNA >1000 copies/mL) with evidence of resistance mutations including the K65R, but without thymidine analogue mutations (TAMs) in genotypic resistance assay. Phenotype was performed from previously collected frozen plasma. The patients were followed for clinical and resistance outcome after treatment intensification with only zidovudine. RESULTS: Five patients had experienced antiretroviral treatment failure on various nucleoside analogue combinations, containing abacavir, didanosine, lamivudine, nevirapine, reverset and/or tenofovir. RT-sequence revealed mutations at position K65R in combination with other non-TAMs. The patients' median viral load prior to zidovudine intensification was 3.551 Log10 (range 3.053-4.681) and despite evidence for resistance to the failing drug regimen, all responded within 4 weeks to undetectable levels (<1.699 Log10 or <50 copies/mL) and remained virologically suppressed during follow-up (20 months through 6.5 years). CONCLUSIONS: In virologically failing patients due to K65R- and other non-thymidine-mutations, simple regimen intensification with zidovudine resulted in sustained HIV-1 suppression. The finding of re-sensitized HIV-1 in patients may be clinically relevant.

Dose reduction effective in alleviating symptoms of saquinavir toxicity.

Gastrointestinal intolerance is a limitation of boosted saquinavir antiretroviral treatment. We present three HIV-infected individuals whose severe toxicity symptoms started directly after initiation of a standard dose saquinavir hard-gel capsule-containing regimen (saquinavir/ritonavir 1000/100 mg). All patients underwent immediate 12 h pharmacokinetic (PK) assessment and showed extraordinarily high saquinavir plasma exposure. All three patients did not recover until the saquinavir exposure was decreased. This pilot case study anticipates a new concept of 'direct PK'-guided individual dose interventions under close viral load monitoring. Two major reasons for symptomatic saquinavir overexposure were defined: impaired liver function in a chronic hepatitis C virus co-infected individual at normal liver performance parameters and a delayed cytochrome p450 enzyme autoinduction. Overexposure seems to be an independent intolerance factor. Although delayed autoinduction is not well established as a reason for adverse events in saquinavir therapy, this observation may be confirmed in the near future by increased use.

[Side effects of antiretroviral treatment for transmission prophylaxis in preterm and near-term infants]. / Unerwünschte Wirkungen der antiretroviralen Prophylaxe der HIV-Transmission bei Frühgeborenen unter 35 Schwangerschaftswochen.

BACKGROUND: The aim of this study was to assess the frequency of side effects of antiretroviral treatment in transmission prophylaxis in preterm and near-term infants with a history of HIV-positive mothers. METHODS: A retrospective single-centre study of all neonates born to HIV-positive mothers between 2001 and 2005 and receiving antiretroviral prophylaxis was performed. Respiratory distress was documented as well as possible side effects from antiretroviral drug treatment, e. g., anaemia, need for transfusion, liver and kidney dysfunction, depression of white blood cell count, feeding problems and nosocomial infections. A comparison was made between a group of preterm infants of less than 35 weeks of gestation with one of near-term neonates of more than 34 weeks. To evaluate the influence of prematurity on the frequency of symptoms, a matched pairs group of 50 preterm infants was established as the control group. RESULTS: Anaemia at birth (24 vs. 27 %), transient signs of liver impairment (24 vs. 16.5 %) or kidney dysfunction (4 vs. 0.8 %) as well as nosocomial infections were not significantly more frequent in the preterm group than in near-term group of HIV-exposed infants. Respiratory distress (56 vs. 13 %), postnatal anaemia (84 vs. 27 %). leucocytopenia (36 vs. 4 %), feeding problems (88 vs. 42 %), and blood transfusion (32 vs. 7 %) were more common in the preterm infants. The frequency of feeding problems remained markedly elevated when preterm HIV-exposed neonates were compared to preterm controls. Respiratory distress in near-term infants was seen in 13 % of the cases and 2.6 % of them had to be ventilated artificially. This was a higher frequency than in babies delivered by elective Caesarean section without maternal HIV history. CONCLUSIONS: Transmission prophylaxis in offspring of HIV-positive mothers may give rise to adverse effects. Their frequency is higher in preterm infants than in near-term infants. However; this may be related to prematurity, and not to the antiretroviral treatment itself.

German-Austrian recommendations for HIV-therapy in pregnancy and in HIV-exposed newborn - update 2005.

In Germany during the last years about 200-250 HIV infected pregnant women delivered a baby each year, a number that is currently increasing. To determine the HIV-status early in pregnancy voluntary HIV-testing of all pregnant women is recommended in Germany and Austria as part of prenatal care. In those cases, where HIV infection was known during pregnancy, since 1995 the rate of vertical transmission of HIV was reduced to 1-2%. - This low transmission rate has been achieved by the combination of anti-retroviral therapy of pregnant women, caesarean section scheduled before onset of labour, anti-retroviral post exposition prophylaxis in the newborn and refraining from breast-feeding by the HIV infected mother. To keep pace with new results in research, approval of new anti-retroviral drugs and changes in the general treatment recommendations for HIV infected adults, in 1998, 2001 and 2003 an interdisciplinary consensus meeting was held. Gynaecologists, infectious disease specialists, paediatricians, pharmacologists, virologists and members of the German AIDS Hilfe (NGO) were participating in this conference to update the prevention strategies. A third update became necessary in 2005. The updating process was started in January 2005 and was terminated in September 2005. The guidelines provide new recommendations on the indication and the starting point for therapy in pregnancies without complications, drugs and drug combinations to be used preferably in these pregnancies and updated information on adverse effects of anti-retroviral drugs. Also the procedures for different scenarios and risk constellations in pregnancy have been specified again. With these current guidelines in Germany and Austria the low rate of vertical HIV-transmission should be further maintained.