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The additional 48-week optional treatment extension of the T-20 versus Optimized Regimen Only (TORO) studies evaluated long-term safety and efficacy of enfuvirtide (ENF) through week 96 in patients receiving ENF plus optimized background (OB) and patients switching to ENF plus OB from OB alone. Patient randomization was 2:1 to ENF plus OB (n = 663) and OB (n = 334), of which 89.7% and 89.8% were male, 89.3% and 88.6% were Caucasian, and median age was 41 and 42 years, respectively. HIV risk factors were comparable between the ENF plus OB and OB groups with the major factors being 65.2% versus 66.2% homosexual contact, 17.8% versus 19.8% heterosexual contact, 4.1% versus 4.8% bisexual contact, respectively, and 6.9% injection drug use in both groups. OB patients were allowed to switch to ENF plus OB at virologic failure before week 48 and required to switch at week 48 to continue in the study (n = 230). Efficacy and safety assessments were conducted for each group. At week 96, 55% of ENF plus OB subjects completed the study and 26.5% achieved a viral load of less than 400 copies per milliliter (17.5% achieved less than 50 copies per milliliter). Viral load and CD4 mean change from baseline was -2.1 and -1.1 [log.sub.10] HIV-1-RNA copies per milliliter and +166 and +116 CD4 cells/[mm.sup.3] for ENF plus OB and switch patients, respectively. No new ENF-related safety issues emerged in weeks 48-96. Injection site reactions led to discontinuation in 7% and 10% of ENF plus OB and switch patients, respectively. In conclusion, these data demonstrate durable efficacy and safety of ENF over 96 weeks and that early use of ENF in combination with other agents for the treatment of antiretroviral-experienced HIV-infected subjects is beneficial.

Studies were conducted to evaluate the expression of the IL-7R alpha chain and to determine the responses of CD4 and CD8 T lymphocytes to IL-7 in three groups of chronically HIV-infected patients. Results reveal that the effects of HAART were less pronounced in patients with undetectable VL but low CD4 counts.

The analysis of pooled safety data from the pivotal phase three T-20 Versus Optimized Background Regimen Only (TORO) trials indicates that enfuvirtide is a well-tolerated antiretroviral agent with a maintained safety profile over 48 weeks in treatment-experienced HIV-1-infected adults. It is found that the rates of other adverse agents favored enfuvirtide or were generally comparable between treatments.

Exploratory analyses to compare treatment effects between the enfuvirtide and control groups by different factors after 48 weeks that were carried out are discussed. It was demonstrated that the efficacy to enfuvirtide is durable plus optimized background over 48 weeks.

The casual pathways by which age and the CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles influence progression to AIDS is investigated. It is concluded that the age and the CCR5-Delta32 deletion and CCR2-64I mutation influence AIDS progression by affecting CD4 and HIV-1 RNA and the SDF-1 3'A allele increases the AIDS risk, but this effect is countered by its effect on CD4 and HIV-1 RNA level.

Recommended antiretroviral regimens include a nucleoside reverse transcriptase inhibitor (NRTI) component and this class of antiretrovirals has problems such as class cross-resistance and mitochondrial toxicity. The lopinavir/ritonavir-efavirenz combination is associated with a high rate of virologic response and should be compared with more classic NRTI-containing regimens in randomized and controlled clinical trials.

The antiviral efficacy and the safety of once-daily atazanavir 400 mg, an azapeptide protease inhibitor (PI), is compared with efavirenz 600 mg, each in combination with open-label fixed-dose zidovudine plus lamivudine twice daily. The results suggest that for initial HIV treatment, a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as effective and well tolerated as the combination of efavirenz/zidovudine/lamivudine.

The patients' knowledge of HIV condition and its treatment are recognized as a factor that influences adherence to antiretroviral therapy, and can be improved through educational programs. An educational intervention improves adherence to antiretroviral regimens and health status and hence should be initiated early in therapy.

Quadruple therapy with saquinavir, nelfinavir and two nucleoside reverse transcriptase inhibitors appears to be more effective in treating HIV infection than triple therapy with only one protease inhibitors. Nelfinavir inhibits an enzyme that metabolizes protease inhibitors, leading to increased blood levels of the drug.

Having the CCR2B-64I receptor does not appear to protect children from HIV infection. In a study of 745 children born to HIV-infected women, this receptor was just as likely to occur in HIV-infected children as in non-infected children.

Protease inhibitors may prevent cytomegalovirus retinal infection in many HIV patients and may slow the progression of existing retinal disease. This was the conclusion of a study of 93 HIV patients taking highly active antiretroviral therapy, which includes the use of protease inhibitors.

Highly active antiretroviral therapy (HAART) appears to lower blood levels of interleukin-10 and raise blood levels of interleukin-12, according to a study of 12 HIV patients. However, blood levels of interleukin-12 are still below normal when compared to levels in non-infected people.