Genotypic tropism testing of proviral DNA to guide maraviroc initiation in aviraemic subjects: 48-week analysis of results from the PROTEST study.

OBJECTIVES: Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infected patients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks. Virological failure was defined as two consecutive viral load measurements > 50 copies/mL. RESULTS: Tropism results were available for 141 of 175 (80.6%) subjects screened: 60% had R5 and 85% of these (n = 74) were finally included in the study. Previous ART included protease inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%. Main reasons for treatment change were dyslipidaemia (42%), gastrointestinal symptoms (22%) and liver toxicity (15%). MVC was given alongside tenofovir (TDF)/emtricitabine (FTC) (54%) and abacavir (ABC)/lamivudine (3TC) (40%) in most patients. Eighty-four per cent of patients maintained a viral load < 50 copies/mL to week 48, whereas 16% discontinued treatment: two withdrew informed consent, one had an R5 to X4 shift between screening and baseline, one was lost to follow-up, one developed an adverse event (rash), two died from non-study-related causes, and five developed protocol-defined virological failure. CONCLUSIONS: Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure for up to 1 year.

Outcome of neuropsychiatric symptoms related to an antiretroviral drug following its substitution by nevirapine: the RELAX study.

OBJECTIVES: The primary objective was to evaluate the improvement in neuropsychiatric symptoms attributed to an antiretroviral drug after that drug was substituted with nevirapine. The secondary objective was to evaluate the impact on patient adherence and quality of life. METHODS: A prospective, observational study was carried out that included patients with HIV-1 plasma suppression for whom an antiretroviral drug was substituted with nevirapine because of central nervous system (CNS) side effects, a Pittsburgh Sleep Quality Index (PSQI) score > 5 or a Hospital Anxiety and Depression Scale (HADS) score ≥ 10, and who had not initiated psychoactive drug treatment during the prior 6 weeks. Evaluations were carried out at baseline and 1 and 3 months after the switch using the PSQI, HADS, Epworth Sleepiness Scale, Medical Outcomes Study-Short Form 30 items (MOS-SF-30) and Simplified Medication Adherence Questionnaire (SMAQ). RESULTS: A total of 129 patients were included in the study. The drug substituted was mainly efavirenz (89.9%), and reasons for the switch included sleep disturbances (75.2%), anxiety (65.1%), depression (38.7%), attention disturbances (31%), and other reasons (31%), with a mean of 2.4 neuropsychiatric disturbances per patient. A statistically significant improvement was observed in all the tests evaluating neuropsychiatric symptoms and adherence at 1 and 3 months. The CD4 lymphocyte count remained stable (P = 0.096). Three (2.3%) patients had a detectable plasma HIV-1 RNA at the end of the study. Nine patients (6.9%) withdrew because of nevirapine-related toxicity (rash in seven patients and hypertransaminasaemia in two patients, none of which were > grade 2). CONCLUSIONS: The switch to nevirapine from a drug causing neuropsychiatric disturbances (primarily efavirenz) in subjects with virological suppression was effective in resolving those disturbances, with an improvement in all the parameters studied. This led to better adherence to treatment and quality of life, with no detrimental effect on their immunological and virological control.

[Pregnancy and HIV infection: the need for routine serological evaluation]. / Embarazo e infección por VIH: necesidad de la evaluación serológica rutinaria.

OBJECTIVES: To determine the frequency of pregnancies among HIV-infected women in a sanitary area. To evaluate the proportion of women not receiving anti-retroviral treatment to decrease vertical transmission and the reasons why this treatment was not administered. PATIENTS AND METHODS: Point prevalence study performed on all women followed for 1997 at the HIV Infection Unit in a 360-bed hospital. The following variables were obtained: social class, civil status and place of residence, risk factors for HIV infection, obstetric antecedents (pregnancies, number of term pregnancies, living newborns) as well as prescription or not of anti-retroviral therapy during pregnancy. RESULTS: Out of 85 women included in the study, 51 (60%) reported to have had a pregnancy and 17 of these (33%) had interrupted the pregnancy at some time. No significant differences were found between pregnancy or abortion and the analyzed socio-demographic variables or risk factors for HIV infection. Only 12% of women with a full length pregnancy received anti-retroviral therapy. Of women with term pregnancy who were not treated, most (63%) did not know they were infected before delivery and an additional 10% refused therapy. Forty-four percent of women with children continued with pregnancy despite knowing they were infected. Vertical transmission occurred in a 13% of cases in which no therapy was instituted and in no case in which zidovudine was administered during pregnancy. CONCLUSIONS: The frequency of pregnancies among HIV-infected women is high in our area and a substantial number of women do not know they are infected. These data support the serological study to HIV in all pregnant women and the necessity of a higher level of information in order that the seropositive women be aware of the responsibility she takes when she decides to go on with her pregnancy.

[Right endocarditis caused by Staphylococcus aureus in parenteral drug addicts: evaluation of a combined therapeutic scheme for 2 weeks versus conventional treatment]. / Endocarditis derecha por Staphylococcus aureus en adictos a drogas por vía parenteral: valoración de un régimen terapéutico combinado de 2 semanas frente al tratamiento convencional.

BACKGROUND: Intravenous drug addicts (IVDA) are a group of patients in whom it is difficult to complete standard treatment of infectious endocarditis due to frequent antisocial behavior and in whom, once clinical improvement is achieved, voluntary discharge is frequently requested. This is why the evaluation of new treatment schedules tending to decrease the length of the same is of great interest. This non randomized study has the aim of knowing the efficacy of a short treatment with cloxacillin or vancomycin associated to gentamicin in right-sided endocarditis by methicillin-sensitive Staphylococcus aureus, comparing this with the standard schedule of 28 days. METHODS: This series was made up of IVDA patients diagnosed of right endocarditis by S. aureus. Inclusion criteria were the presence of intravenous drug addiction, isolation of methicillin-sensitive S. aureus in 2 or more blood cultures and achievement of the diagnostic criteria of right-sided endocarditis. Two schedules were used: a) standard: cloxacillin or vancomycin for 4 weeks, associating aminoglucoside in the first 3-5 days; b) short; cloxacillin or vancomycin associated to gentamicin for 2 weeks with no ulterior treatment. The study was not randomized and the treatment of 2 weeks was compared with historic controls treated for 4 weeks. The criteria evaluated were those of clinical cure, relapse, appearance of complications during treatment and mortality. RESULTS: Both the standard treatment and the combination of cloxacillin or vancomycin with gentamicin for 2 weeks cured 100% of the episodes of right endocarditis by S. aureus. There were no relapses and mortality was nul. Neither were there any differences between the two groups with regard to appearance of complications. CONCLUSIONS: In intravenous drug addict patients with right-sided endocarditis by methicillin S. aureus, the association of cloxacillin and gentamicin for 2 weeks is an effective alternative to long (4 week) treatments with only one antibiotic. The low number of cases treated with vancomycin does not allow conclusions to be drawn on its efficacy.