Future Hiv Therapy 

About: Future Hiv Therapy is an academic journal. The journal publishes majorly in the area(s): Acquired immunodeficiency syndrome (AIDS) & Viral load. Over the lifetime, 99 publications have been published receiving 640 citations.

Update on the development of HIV entry inhibitors

Abstract: HIV entry and fusion are two steps in the viral life cycle that can be targeted by several classes of antiviral drugs. The discovery of chemokines focused the attention on cellular coreceptors used by the virus for entering within cells, and to the various steps of such processes which are subject to interactions with small molecules. Intense research led to a wide range of effective compounds that are able to inhibit these initial steps of viral replication. All steps in the process of HIV entry into the cell may be targeted by specific compounds that may be developed as novel types of antiretrovirals. Thus, several inhibitors of the gp120-CD4 interaction have been detected so far (zintevir, FP-21399 and BMS-378806 in clinical trials). Small molecule chemokine receptor antagonists acting as HIV entry inhibitors also were described in the last period, which interact both with the CXCR4 coreceptor (such as AMD3100; AMD3465; ALX40-4C; T22, T134 and T140), or which are antagonist of the CCR5 coreceptor (TAK-779, TAK-220, SCH-C, SCH-D, E913, AK-602 and NSC 651016 in clinical trials), together with new types of fusion inhibitors possessing the same mechanism of action as enfuvirtide (such as T1249). Recently, a third family of antivirals started to be used clinically (in addition to the reverse transcriptase and protease inhibitors), with the advent of enfuvirtide (T20), the first fusion inhibitor to be approved as an anti-HIV agent. Some of these compounds demonstrated in vitro synergism with other classes of antivirals, offering thus the rationale for their combination in therapies for HIV-infected individuals. Many HIV entry and fusion inhibitors are currently investigated in controlled clinical trials, and there are a number of them that is bioavailable as oral formulations. This is an essential feature for an extended use of these compounds with the purpose of ameliorating adherence of patients to these medications and preventing the development of drug resistance.

Male circumcision is an efficacious, lasting and cost-effective strategy for combating HIV in high-prevalence AIDS epidemics

Abstract: The authors respond to a recent article “Male circumcision is not the ‘vaccine’ we have been waiting for!” Green et al. claim that the incorporation of male circumcision (MC) as an additional HIV prevention strategy is based on ‘incomplete evidence and is premature and ill-advised’.

Oxidative stress and HIV infection: Target pathways for novel therapies?

Abstract: Oxidative stress is thought to play an important role in the progression of HIV infection. fact, it has been observed that perturbations in antioxidant defense systems, and consequently redox imbalance, are present in many tissues of HIV-infected patients. Moreover, there is clear evidence that oxidative stress may contribute to several aspects of HIV disease, including viral replication, inflammatory response and decreased immune cell proliferation. For this reason, the exogenous supply of antioxidants, as natural compounds and new-generation antioxidants that scavenge free radicals, might represent an important additional strategy for the treatment of HIV infection in the era after HAART therapy has been applied.

14th Conference on Retroviruses and Opportunistic Infections (CROI 2007)

Abstract: In the category ‘Best new drug’: raltegravir This integrase inhibitor was previously called MK-0518 and will have the trade name Isentress® (Merck). In Los Angeles, results from two Phase III trials, called Benchmrk 1 and 2, were presented. In both trials, patients with advanced HIV infection and multi-resistant viruses were recruited in the USA (Benchmrk 2) and in the rest of the world (Benchmrk 1) [1,2]. An optimal background treatment (OBT) was constructed with conventional drugs and resistance tests. To OBT, either placebo or raltegravir, 400 mg/twice daily, were added. Results from Benchmrck 1 are shown in Table 1. These are excellent results in such an advanced patient population; additional good news was the absence of any identifiable side effect that could plausibly be attributed to raltegravir, and a pharmacokinetic profile suggesting that drug interactions will be few. It is a safe bet that such a powerful drug will select resistance mutations; indeed, in patients from a Phase II study already presented at the Toronto Conference, two typical resistance mutations emerged, namely N155H and Q148H/K/S. With these results, submission to the US FDA will probably occur soon and approval, at least for advanced patients with multiresistance, might be granted as early as the second quarter of 2007. There are plans to use raltegravir earlier, in patients who have less-resistant virus or are even treatment naive. Studies in these patient populations are in progress. One handicap is the twicedaily administration, but pharmacokinetic data suggest that raltegravir will also be active once daily. Combination pills have proven to be very successful; we can anticipate that raltegravir will be paired with other new substances. In contrast to other new drugs such as darunavir or TMC-125 that, although effective, are more cubersome to use, raltegravir has a real chance to become part of the basic treatment regimen in most types of HIV-infected patients. A second integrase inhibitor formally called GS-9137 (Gilead) [2] has now morphed into elvitegravir. In contrast to raltegravir, it needs boosting by ritonavir, and is administrated once daily. In a Phase study, 20 mg/day was ineffective, whereas higher doses, particularly 125 mg/day combined with 100 mg of ritonavir, reduce viral load more than the background regimen (Table 2), without noticeable side effects. However, in cases where elvitegravir was the only active substance, resistance development was quite rapid.

Is male circumcision as good as the HIV vaccine we’ve been waiting for?

Abstract: What would the reaction of the international public health community have been if a year ago scientists had announced the discovery of a vaccine or chemical gel that, in three separate clinical trials, had reduced the risk of heterosexual HIV infection in men by at least 60%? Considering that even with increasing access to antiretroviral therapy AIDS continues to be a huge killer – every day over 2,000 men become infected with HIV in sub-Saharan Africa alone [1], which eventually also results in millions of new cases in their partners and children – would not such an announcement have surely sparked a massive surge of excitement and renewed investment in HIV prevention?