Time to virological failure with atazanavir/ritonavir and lopinavir/ritonavir, with or without an H2-receptor blocker, not significantly different in HIV observational database study.

A retrospective electronic database study was conducted to determine any differences in time to virological failure and percent of virological failure among HIV-infected patients concurrently receiving H2-blockers versus patients not receiving these agents while receiving atazanavir (ATV)/ritonavir (r) or lopinavir (LPV)/r-containing antiretroviral treatment regimens. Data were culled from October 2003 (when ATV became commercially available) through February 2006. Virological failure was defined as (1) two plasma HIV-1 RNA levels >400 copies/mL after at least one HIV-1 RNA level below the level of detection or (2) failure to achieve an HIV-1 RNA <400 copies/mL within 24 weeks. Data from 267 ATV/r-treated patients who met the case definition were compared with data from 670 LPV/r-treated patients. Approximately 10% of the ATV/r group received concurrent H2-blockers when compared with 20% of the LPV/r group. Multivariate analysis showed no statistically significant differences regarding time to virological failure between or among the four subgroups, adjusting for differences in baseline characteristics (P = 0.79, log-rank test). At 750 days following treatment initiation, the proportion of patients not experiencing virological failure was 56% in the ATV/r-blocker subgroup, 48% in the ATV/r-alone subgroup, 45% in the LPV/r-alone subgroup and 42% in the LPV/r-blocker subgroup.

Comparison of nevirapine- and efavirenz-containing antiretroviral regimens in antiretroviral-naïve patients: a cohort study.

OBJECTIVE: Efavirenz (EFV) was superior to nevirapine (NVP) in two recent cohort studies; but data from clinical trials suggest that three studies are needed to validate cohort results. We performed a cohort analysis comparing time to treatment failure and change in plasma HIV-1 RNA from baseline in antiretroviral therapy (ART)-naïve individuals treated with NVP- or EFV-containing regimens. METHOD: A cohort analysis of three observational databases (N = >10,000 patients) found 1,078 ART-naïve individuals treated with NVP-containing (n = 523) or EFV-containing (n = 555) regimens. Patients were evenly matched and received at least three antiretroviral agents. The primary endpoint was time to treatment failure defined as a rebound in plasma HIV-1 RNA > 400 copies/mL. Other endpoints were change in plasma HIV-1 RNA from baseline and percent with plasma HIV-1 RNA <400 copies/mL over time. Potential confounding variables were analyzed using the Cox proportional hazards model. RESULTS: Compared to EFV, NVP patients had a shorter time to treatment failure (307 days vs. 589 days; p <.001), less decrease in plasma HIV-1 RNA (-0.51 log vs. -1.32 log; p <.001), and fewer patients with plasma HIV-1 RNA < 400 copies/ mL (45% vs. 51%; p <.001). Significant factors for failure were baseline CD4 count (per 100 cell increase) or viral load (per log increase), treatment center, and year of entry (p <.05 for all comparisons). Race, gender, and background nucleoside use were insignificant factors. Multivariate analysis that included significant factors for failure demonstrated improved relative hazard with EFV compared to NVP (odds ratio = 0.50, p <.001). CONCLUSION: EFV-containing antiretroviral regimens were associated with superior clinical outcome, as measured by time to treatment failure. Results are commensurate with other large cohort studies comparing EFV and NVP.

Trizivir.

Treatment of HIV infection has typically been carried out using two nucleoside analogues and a protease inhibitor (PI). Such regimens can be complex and have high pill burdens. Use of alternative regimens, such as triple nucleoside based regimens, can improve adherence and decrease toxicities associated with PI therapy. Trizivir is a combination tablet of zidovudine, lamivudine and abacavir. This formulation allows a dosing schedule of one pill twice-daily. The components of have performed favourably compared to PI-based regimens, such as indinavir. However, in one study the individual components of Trizivir did not suppress HIV-1 viral replication as well as the PI-based regimen in a subset of patients with very high HIV-1 plasma RNA. Trizivir also avoids side effects of antiretroviral therapy, such as hyperlipidaemia, but its use is associated with a hypersensitivity reaction in a small number of patients. Trizivir is an important part of the HIV armamentarium. The potency and ease of administration of Trizivir make it worth consideration in HIV therapy, either by itself or in combination with other agents.

Comparison of symptoms of influenza A with abacavir-associated hypersensitivity reaction.

Differentiation between abacavir hypersensitivity and viral respiratory infections is problematic. Fifteen cases of abacavir hypersensitivity were matched to 30 controls with culture proven influenza A with no abacavir exposure. Rash was associated with hypersensitivity (odds ratio [OR] = 13.1, P = 0.02) as was the presence of nausea (OR = 30, P < 0.001), vomiting (OR = 17.1, P = 0.001) or diarrhoea (OR = 22, P < 0.001). The number of gastrointestinal symptoms was also predictive of hypersensitivity reaction (P < 0.001). Respiratory symptoms (cough, sore throat, or dyspnoea) were not associated with abacavir hypersensitivity (OR = 0.08, P = 0.001). Multivariate analysis confirmed the following associations for abacavir hypersensitivity: the number of gastrointestinal symptoms (OR = 8.6, P = 0.0032), cough (OR = 0.039, P = 0.02) and rash (OR = 16.9, P = 0.07). Abacavir hypersensitivity is strongly associated with gastrointestinal (GI) symptoms. Cough without GI symptoms is associated with influenza.

A man with oral lesions, constipation and back pain.

We describe an unusual presentation of disseminated Kaposi sarcoma in a 49-year-old African-American man with AIDS who was admitted to the hospital for constipation and back pain. Magnetic resonance imagings of the thoracic and lumbar spine were grossly abnormal, however, a biopsy of the iliac crest was interpreted as normal. The patient remained a diagnostic enigma until disseminated Kaposi sarcoma was suspected, based on vascular plaque-like lesions observed on his hard palate and right conjunctiva. Slides of the bone biopsy with were stained for human herpes virus-8 (HHV-8) antigen, and were positive. AIDS-related skeletal manifestations of Kaposi sarcoma have been reported in the literature but are infrequent.

Abacavir sulfate/lamivudine/zidovudine fixed combination in the treatment of HIV infection.

Treatment of HIV infection has typically been carried out using two nucleoside analogs and a protease inhibitor. Such regimens can be complex and have high pill burdens. Use of alternative regimens, such as triple nucleoside-based regimens, can improve adherence and decrease toxicities associated with protease inhibitor therapy. A formulation of abacavir sulfate/lamivudine/zidovudine allows a dosing schedule of one pill twice daily. The components have performed favorably compared with protease inhibitor-based regimens, such as indinavir. Compared with efavirenz-based regimens, abacavir sulfate/lamivudine/zidovudine has not performed as well. The combination is being studied as a cornerstone for induction maintenance strategies, in which switching a patient to abacavir sulfate/lamivudine/zidovudine has been associated with similar virologic outcomes as continuing with either protease inhibitor- or efavirenz-based regimens. Administration of abacavir sulfate/lamivudine/zidovudine also avoids side effects of antiretroviral therapy, such as hyperlipidemia, but its use is associated with a hypersensitivity reaction in a small number of patients. The combination of abacavir sulfate/lamivudine/zidovudine is an important part of the HIV armamentarium. Its potency and ease of administration make it worth consideration in the treatment of HIV, either by itself or in combination with other agents.