Search

Purpose: Hitherto, studies on highly active antiretroviral therapy (HAART) initiation have shown partly inconsistent results. Our study investigated the clinical course and course of immune status after HAART initiation at CD4-cell-count/μl of treated patients between 250 and 349 (group 1), compared to 350-449 (group 2), on the basis of the cohort of the Competence Network for HIV/AIDS (KompNet cohort)., Methods: Patients had to be HAART-naïve. Medication had to start at the earliest in 1996, being at least triple combination therapy. The primary endpoints of death, first AIDS-defining illness and first drop of CD4-cell-count/μl below 200 were evaluated as censored event times between the initiation of HAART (t (0)) and the date of the first event/date of last observation. Probabilities of event-free intervals since t (0) were calculated by Kaplan-Meier estimation, compared by logrank tests. The results were adjusted for confounders using Cox regression. Additionally, incidences were estimated., Results: A total of 822 patients met the inclusion criteria (group 1: 526, group 2: 296), covering 4,133 patient years (py) overall. In group 1, 0.64 death cases/100 py were found, with the corresponding vale being 0.17 in group 2. In group 1, 1.38 AIDS-defining events/100 py occurred, whereas it was 0.78 in group 2. In group 1, 2.64 events of first drop of CD4-cell-count/μl below 200 occurred per 100 py, compared to 0.77 in group 2. Kaplan-Meier estimations showed borderline significant differences regarding death (p = 0.063), no differences regarding first AIDS-defining illness (p = 0.148) and distinct differences regarding the first drop of CD4-cell-count/μl below 200 (p = 0.0004)., Conclusions: The results gave a strong hint for a therapy initiation at higher CD4-cell-count/μl regarding the outcome of death in treated patients. A distinct benefit was shown regarding the first decline of CD4-cell-count/μl below 200.

Background: Clinical studies suggest expert recommendations as a possibility to optimize highly active antiretroviral therapy (HAART) in patients with multi-drug resistant virus strains. An online system (RADATA) has been developed to provide expert advice for the drug therapy of HIV-infected patients., Objective: To evaluate the efficacy of expert-advice-guided HAART switches in patients with triple-class failure., Methods: Virological and immunological outcome of patients having undergone at least three prior ART regimens, including nucleoside inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI) use, were analyzed. Changes in HIV-RNA and CD4-cell count were evaluated every 3 months., Results: 183 patients with a median baseline viral load of 3.90 log copies/ml (1.88-6.54 log) and a CD4-cell count of 298 c/ll (5-910 c/ll) were eligible for analysis. The patients had a median of seven prior ART regimens and a treatment duration of 83 months. A median of three (range 0-8) NRTI-, two (0-7) thymidine-associated (TA), one (0-4) NNRTI-, and three (0-13) PI-associated resistance mutations were present at baseline. Despite available resistance analyses and expert recommendations, 66% (n = 119) of the patients started a new ART regimen without any active drugs according to the resistance analysis. The HIV-RNA declined by a median of 0.61 log and 0.92 log after 12 and 24 months, respectively, while the CD4-cell count rose by a median of +9 c/microl and +25 c/microl during this period. No significant differences related to number of prior regimens or number of active substances used could be found., Conclusion: Despite extensive pre-treatment and multiple resistances against prescribed HAART, our patients demonstrated a decline in viral load and a stable CD4-cell count over the observation period. We conclude that the activity of antiretroviral regimens is not exclusively explained by the current algorithms used for estimating antiretroviral drug activity.

Objectives: Among people with HIV, we examined symptom attribution to HIV or HIV-therapy, awareness of potential side effects and discontinuation of treatment, as well as sex/gender differences., Methods: HIV-patients (N=168, 46% female) completed a comprehensive symptom checklist (attributing each endorsed symptom to HIV, HIV-therapy, or other causes), reported reasons for treatment discontinuations and potential ART-related laboratory abnormalities., Results: Main symptom areas were fatigue/sleep/energy, depression/mood, lipodystrophy, and gastrointestinal, dermatological, and neurological problems. Top HIV-attributed symptoms were lack of stamina/energy in both genders, night sweats, depression, mood swings in women; and fatigue, lethargy, difficulties concentrating in men. Women attributed symptoms less frequently to HIV than men, particularly fatigue (p<.01). Top treatment-attributed symptoms were lipodystrophy and gastrointestinal problems in both genders. Symptom attribution to HIV-therapy did not differ between genders. Over the past six months, 22% switched/interrupted ART due to side effects. In women, side effect-related treatment decisions were more complex, involving more side effects and substances. Remarkably, women took predominantly protease inhibitor-sparing regimens (p=.05). Both genders reported only 15% of potential ART-related laboratory abnormalities but more than 50% had laboratory abnormalities. Notably, women had fewer elevated renal parameters (p<.01)., Conclusions: Men may attribute symptoms more often to HIV and maintain a treatment-regimen despite side effects, whereas women may be more prudent in avoiding treatment side effects. Lacking awareness of laboratory abnormalities in both genders potentially indicates gaps in physician-patient communication. Gender differences in causal attributions of symptoms/side effects may influence treatment decisions.

CCR5 antagonists are a newly developed class of antiretroviral drugs which inhibit viral entry into the host cell by binding to the predominant HIV coreceptor. Data on the use of these new drugs in treatment-experienced HIV patients are emerging. Clinical trials on maraviroc and vicriviroc in pretreated patients recruited more than 1300 individuals. Interim results of these studies indicate that pretreated patients infected with CCR5-tropic viruses benefit from their use in optimized combination regimens. Maraviroc reduces the HIV-1 viral load in patients with previous triple-class failure by 1.96 log10 copies/ml versus 0.99 log10 copies/ml in placebo; vicriviroc shows potency by dose depending viral decrease of 1.51-1.68 log10 copies/ml compared to 0.29 log10 in placebo. As expected, CCR5 antagonists do not reduce viral load in patients harbouring CXCR4-tropic or dual/mixed tropic viruses. Nevertheless, since a considerable percentage of late-stage HIV patients still bear CCR5-tropic viruses, the use of CCR5 antagonists appears promising in properly selected treatment-experienced patients.

We describe the first Mycobacterium haemophilum infection that occurred in a patient with human immunodeficiency virus in Germany and report 7 newly diagnosed cases of M. haemophilum infection. In the former case, a local M. haemophilum skin infection resolved as a result of successful antiretroviral therapy only; however, that clinical outcome may not be possible for more invasive forms of the disease.

Background: After the discontinuation of antiretroviral therapy in HIV-infected patients with highly resistant virus, the detectability of viral resistance mutations quickly decreases. To which extent this represents a true loss of resistance or rather a detectability phenomenon remains unclear., Objectives: To monitor virologic response and resistance pattern during a non-strategic treatment interruption in the presence of highly drug-resistant viral strains., Study Design: We performed serial genotypic resistance analyses on viral DNA isolated from a patient with a multidrug-resistant human immunodeficiency virus infection who discontinued and later on reintroduced antiretroviral therapy. Sequencing was performed on viral DNA from plasma as well as DNA from circulating leukocytes., Results: While under combination antiretroviral therapy with two nucleosidic reverse transcriptase inhibitors, a non-nucleosidic reverse transcriptase inhibitor and a protease inhibitor, the viral load of the patient was around five logs. Genotypic resistance to all available agents was detected during this time. Antiretroviral therapy was then interrupted, and 14 weeks later an almost complete reversion of the virus to wild type was observed. After introduction of a new antiretroviral therapy regimen, the reappearance of nearly all of the formerly present resistance mutations had to be noted within 6 weeks, including mutations without known relation to any of the drugs in the new regimen., Conclusions: We obviously observed not the de novo appearance of a complex resistance pattern under just 6 weeks of potent antiretroviral therapy, but a reappearing archival strain of the virus. This finding provides evidence for subdetectable persistence of resistant variants during treatment interruptions. Therefore, resistance analyses from peripheral blood performed in times of treatment interruptions should be interpreted with caution as they may provide incomplete information about the resistance profile soon after reintroduction of therapy.

Objective: To assess HIV-1 isolate based resistance profiles from extensively pretreated patients and effects of a resistance guided switch of antiretroviral therapy., Methods: In a prospective study phenotypic and genotypic resistance analyses were performed on HIV infected individuals with failure of the current therapy and history of at least three antiretroviral regimens. Antiretroviral therapy was changed according to the results. Viral load and CD4 lymphocyte counts were measured at baseline, after 10 (SD 2), and 24 (2) weeks., Results: All patients (n=52) failed their actual regimen. Currently versus ever previously taking the specific drug, resistance associated mutations and phenotypic resistance to AZT and 3TC were found in over 80% of individuals; resistance to DDI and D4T was detected in less than 10% of cases. A resistance guided switch of therapy was followed by a median decrease of viral load of 0.5 log10 units after 24 weeks. Individuals resistant to two or more drugs compared with patients with resistance to less than two drugs of ongoing treatment, were switched to a regimen containing DDI, D4T, and a PI or NNRTI. After 10 (SD 2) weeks viral load decrease was pronounced in patients with resistance to at least two drugs in the previous regimen., Conclusions: Among different RTI, the profile of clinically relevant resistance indicates pronounced differences when looking at separate drugs. Regarding virological response, in the context of available drugs, resistance tested with currently used methods is of limited value in extensively pretreated patients and seems to have its value primarily in first or second switch of therapy.