Prevalence and incidence of Toxoplasma infection in HIV-positive patients in the Czech Republic.
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Adolescent↗
Biomedical subjects
Ladislav Machala
Publications and source records attributed to Ladislav Machala.
[Prophylaxis of the vertical transmission of the human immunodeficiency virus (HIV) in the Czech Republic].
GOAL: To assess the efficacy of prophylactic measures intended to reduce vertical transmission of HIV infection and to evaluate the predictive value of demographic, immunological and virological factors for determination of the risk of HIV transmission to fetus and neonate. METHODS: 56 pregnancies of 53 HIV-positive women were included in this retrospective study. The women have been in the care of the AIDS Centre of the Dpt. of Infectious Diseases, University Hospital Na Bulovce over the past 15 years. Cellular immunity tests and HIV RNA viral load in all subjects were regularly determined. In line with our present knowledge and the patients compliance, we introduced prophylactic measures, which included the administration of antiretroviral agents, delivery by Caesarean section and breast-feeding avoidance. 58 children were born from these pregnancies and repeated blood tests were performed to detect the presence or absence of HIV RNA. RESULTS: 58 infants were born from 56 pregnancies-and 3 of them (5.17%) were infected with HIV. In two mothers, we diagnosed HIV positivity few hours before delivery; another woman was diagnosed early, however, the failure of treatment was due to her insufficient compliance. In addition, premature amniorrhoea was present in two women. Moreover, one of them presented with untreated syphilis. The other 55 children stayed uninfected. In six of them, however, prophylactic measures were not fully followed, mainly because the patients disregarded them. CONCLUSIONS: The study fully confirms the high efficacy of prophylactic measures, which substantially reduce the risk of vertical transmission of HIV infection. Routine blood tests are necessary in all pregnant women by law. The failure of prophylaxis is in most cases due to inadequate compliance with the treatment. However, we cannot rule out the possible resistance to antiretroviral agents.
Czech Republic↗
Response of HIV positive patients to the long-term salvage therapy by lopinavir/ritonavir.
BACKGROUND: The cohort of 19 patients on LPV/r salvage regimen was followed for the period of up to 37.5 months. Patient's virologic response was evaluated with regard to the various baseline characteristics. RESULTS: A 73.7% of patients (14 out of 19) achieved viral suppression during the first three months of treatment, either complete (47.4%) or partial (26.3%). This effect was only transient in five cases (virologic rebound emerged after 9 months of treatment on average) and in nine cases the treatment was successful in the long-term analysis (HIV RNA plasma level still undetectable at 31st month of the therapy on average with maximum of 36 months). We analyzed the link between the virologic response and possible predictive factors of treatment efficiency, such as lopinavir mutation score, various individual mutations, previous PI exposure, etc. We also describe changes in the PR sequence associated with poor response to the salvage therapy to LPV/r. CONCLUSIONS: The results of LPV/r salvage therapy were encouraging. About 47% of patients from our study achieved stable suppression of viral replication for 31 months on average. LPV/r proved to be potent inhibitor despite unfavourable prognosis.
Adult↗
Rate of viral rebound according to specific drugs in the regimen in 2120 patients with HIV suppression.
BACKGROUND: It is currently unclear whether the tendency for viral rebound in patients with viral load < 50 copies/ml differs according to the specific drug regimen being used. METHODS: To follow 2120 patients in EuroSIDA who had attained < 50 copies/ml on highly active antiretroviral therapy (HAART), without previously virologically failing HAART. RESULTS: The rate of viral rebound (two consecutive values > 400 copies/ml) was 4.9/100 person-years [95% confidence interval (CI), 4.0-5.8] for patients who were naive pre-HAART and 8.0/100 person-years (95% CI, 7.0-9.0) for those who were experienced with nucleoside analogue reverse transcriptase inhibitors (NRTI) pre-HAART. The rate of rebound was significantly higher in those taking nelfinavir than in those taking efavirenz, both in patients who were naive pre-HAART and those who were NRTI experienced [adjusted rate ratios, 2.83 (95% CI, 1.51-5.31) and 2.86 (95% CI, 1.65-5.00), respectively]. Among patients who were naive pre-HAART, those on abacavir had no evidence of a raised risk of viral rebound (adjusted rate ratio 1.17; 95% CI, 0.51-2.69), but in those with pre-HAART NRTI experience the rate was markedly raised (adjusted rate ratio, 4.48; 95% CI, 2.51-8.00). A similar picture was seen when comparing those on nevirapine with those on efavirenz, although the elevated rate ratio in pre-HAART experienced patients was of lower magnitude (adjusted rate ratio, 1.93). There was no strong evidence that rebound rates differed significantly for any NRTI pairs compared with zidovudine/lamivudine. CONCLUSION: Viral rebound rates in patients who have attained < 50 copies/ml appear to differ according to the specific drugs being used.
Adult↗
Predictors of immunological failure after initial response to highly active antiretroviral therapy in HIV-1-infected adults: a EuroSIDA study.
BACKGROUND: Factors that determine the immunological response to highly active antiretroviral therapy (HAART) are poorly defined. OBJECTIVE: Our aim was to investigate predictors of immunological failure after initial CD4(+) response. METHODS: Data were from EuroSIDA, a prospective, international, observational human immunodeficiency virus (HIV) type 1 cohort. RESULTS: Of 2347 patients with an increase in CD4(+) cell count >or=100 cells/microL within 6-12 months of the initiation of HAART, 550 (23%) subsequently experienced immunological failure (CD4(+) count less than or equal to the pre-HAART value). The incidence of failure was 11.6 incidences/100 person-years of follow-up (95% confidence interval [CI], 10.2-13.4) during the first 12 months and decreased significantly over time (P<.0001). Independent predictors of immunological failure were pre-HAART CD4(+) cell count (per 50% higher; relative hazard [RH], 2.05; 95% CI, 1.83-2.31; P<.0001), time-updated virus load (per 1 log(10) higher; RH, 1.77; 95% CI, 1.64-1.92; P<.0001), and HIV-1 risk behavior (P=.047 for a global comparison of risk groups). CONCLUSION: The risk of immunological failure in patients with an immunological response to HAART diminishes with a longer time receiving treatment and is associated with pretreatment CD4(+) cell count, ongoing viral replication, and intravenous drug use.
Adult↗
[Enfuvirtide].
Enfuvirtide is the first representative of a new group of antiretrovirals - fusion inhibitors, which was approved for clinical use. Due to its attachment to the HR1 domain of HIV glycoprotein gp 41 enfuvirtide blocks the fusion between the virus and the target cell. Enfuvirtide is chemically a synthetic peptide consisting of 36 amino acids which is not stable in GIT and must be administered only subcutaneously. Enfuvirtide has been registered for the use as salvage therapy of patients with multiresistance, for who it is not possible to constitute an effective combination of other available antiretrovirals.
Journal Article↗
[Inappropriate combinations of antiretroviral drugs].
At present 19 antiretroviral drugs are available, which offer together 969 possible triple-combinations. Only a few combinations, mainly of nucleoside inhibitors of reverse transcriptase, are contraindicated due to undesirable interactions, which may negatively influence the treatment efficacy or increase toxicity. With raising number of antiretroviral drugs there must also be paid more attention to possible interactions of these drugs.
Anti-Retroviral Agents↗
Unusual binding mode of an HIV-1 protease inhibitor explains its potency against multi-drug-resistant virus strains.
Protease inhibitors (PIs) are an important class of drugs for the treatment of HIV infection. However, in the course of treatment, resistant viral variants with reduced sensitivity to PIs often emerge and become a major obstacle to successful control of viral load. On the basis of a compound equipotently inhibiting HIV-1 and 2 proteases (PR), we have designed a pseudopeptide inhibitor, QF34, that efficiently inhibits a wide variety of PR variants. In order to analyze the potency of the inhibitor, we constructed PR species harboring the typical (signature) mutations that confer resistance to commercially available PIs. Kinetic analyses showed that these mutated PRs were inhibited up to 1,000-fold less efficiently by the clinically approved PIs. In contrast, all PR species were effectively inhibited by QF34. In a clinical study, we have monitored 30 HIV-positive patients in the Czech Republic undergoing highly active antiretroviral therapy, and have identified highly PI resistant variants. Kinetic analyses revealed that QF34 retained its subnanomolar potency against multi-drug resistant PR variants. X-ray crystallographic analysis and molecular modeling experiments explained the wide specificity of QF34: this inhibitor binds to the PR in an unusual manner, thus avoiding contact sites that are mutated upon resistance development, and the unusual binding mode and consequently the binding energy is therefore preserved in the complex with a resistant variant. These results suggest a promising route for the design of second-generation PIs that are active against a variety of resistant PR variants.
Amino Acid Substitution↗