Treatment
Lori F, Foli A, Kelly LM, Lisziewicz J. Virostatics: a new class of anti-HIV drugs. Curr Med Chem 2007;14:233-41.
Lori and colleagues discuss in this review article we discuss the features of a new class of antiretroviral combinations, namely "Virostatics". Virostatics are characterized by the combination of a drug directly inhibiting virus production (viro), and another drug indirectly inhibiting the virus by reducing cellular proliferation (static). In particular, we will focus on the combination of hydroxyurea and didanosine against HIV-1. Hydroxyurea and didanosine synergize to control viral replication and present with a favourable resistance profile, suppressing several resistant quasi-species. Because virostatics target essential cellular proteins, they exert an immune modulating activity and reduce viral targets (CD4 T cells), possibly with limited immunosuppressive effects. Importantly, a dose-finding clinical study has shown that decreasing the dose of hydroxyurea not only diminishes toxicity but also increases antiviral potency. Therefore, the combination of hydroxyurea and didanosine strikes a balance between viral suppression, drug-related toxicity and viral escape, and could have a role both in induction and maintenance therapy. The authors appraise what is known about hydroxyurea and didanosine and specifically address the major advantages, i.e. novel mechanism of action leading to a new class of drugs and resistance profile providing durability, as well as the major criticisms of this combination, i.e. toxicity and reasons for prescribing a perceived immune suppressant to immune compromised patients.
Editors’ note: This concept builds on the knowledge that part of the immune deficiency in HIV is the result of the body’s own response in destroying HIV infected T-cell lymphocytes. Further study is needed to see if the promise of virostatic drug combinations is real.
Erikstrup C, Kallestrup P, Zinyama R, Gomo E, Mudenge B, Gerstoft J, Ullum H. Predictors of mortality in a cohort of HIV-1-infected adults in rural africa. J Acquir Immune Defic Syndr 2007 Jan 25; [Epub ahead of print]
CD4 cell count and plasma HIV RNA level are used to monitor HIV-infected patients in high-income countries, but the applicability in an African context with frequent concomitant infections has only been studied sparsely. Moreover, alternative inexpensive markers are needed in the attempts to roll out antiretroviral treatment in the region. Erikstrup and colleagues explored the prognostic strengths of classic and alternative progression markers in this study set in rural Zimbabwe. The authors followed 196 treatment-naive HIV-1-infected patients from the Mupfure Schistosomiasis and HIV Cohort, Zimbabwe. CD4 cell count, HIV RNA level, hemoglobin (HB), total lymphocyte count (TLC), body mass index, clinical staging (Centers for Disease Control and Prevention [CDC] classification), and self-reported level of function (Karnofsky Performance Scale score) were assessed at baseline; participants were followed until death or last follow-up (3-4.3 years). All parameters except TLC predicted survival in univariate Cox models. HIV RNA level (P = 0.001), HB (P = 0.018), CD4 cell count (P = 0.047), and CDC category C (P = 0.007) remained significant in multivariate analysis. The authors conclude that HIV RNA level and CD4 cell count predict mortality with prognostic capabilities similar to findings from high-income countries. As well, hemoglobin and clinical staging were strong independent predictors and might be considered candidates for alternative HIV progression markers.
Editors’ note: Although haemoglobin is often more easily available than RNA levels and CD4 counts, it is not specific to HIV and therefore cannot be relied on to assess HIV progression on its own.
Wanchu A, Bhatnagar A, Bambery P, Singh S, Varma S. Prevention of opportunistic infections in HIV infection by pentoxiphylline. Indian J Med Res 2006;124:705-8.
Levels of tumour necrosis factor (TNF) are increased in patients with HIV infection leading to increased apoptosis and reduced CD4 cell life. Pentoxiphylline is a TNF inhibitor with properties that might make it useful for the treatment of HIV infection. These include improved cell mediated immunity and inhibition of viral replication. Wanch and colleagues carried out this study to determine the therapeutic utility of pentoxiphylline in improving constitutional manifestations, preventing opportunistic infections and sustaining CD4 counts among asymptomatic HIV infected individuals (i.e., those with no opportunistic infection). Individuals with HIV infection who were over 18 yr of age and free of opportunistic infections were recruited and followed up 4 weekly. Pentoxiphylline was prescribed in a dose of 400 mg thrice daily. Thirty three (18 males) patients with HIV infection were studied. During their follow up (mean 12.5 +/- 5.6 months) one patient each developed cryptococcal meningitis and fibrocavitary tuberculosis. Weight increased from 51.3 +/- 7.4 kg at baseline to 55.3 +/- 7.4 kg (P<0.05). Malaise, fatigue and appetite improved in all those with these complaints, except the two with opportunistic infections. Mean CD4 counts were 184 +/- 36.4/mul at baseline and increased to 210 +/- 28.6/mul(3) at four weeks (P<0.05). The patients had stable CD4 counts over the follow up period since then, i.e., within 25 per cent of the previous levels. The authors concluded that pentoxiphylline therapy in HIV infected individuals, who were free of opportunistic infections, improved their body weight, minimized opportunistic infections, increased and sustained CD4 counts. Given the low cost of the drug it could be recommended for the use in individuals who are at a high risk of developing opportunistic infections.
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