Optimal Antiretroviral Regimens Research Articles

Kidney Transplantation in Patients with HIV.

Individuals with HIV are at increased risk for ESKD. Kidney transplantation is the best treatment for ESKD in the HIV+ population. Despite reduced access to transplantation, patients who are HIV+ have excellent outcomes and clearly benefit from receiving one. Common post-transplant complications and management concerns, including the optimal antiretroviral regimen, immunosuppression protocols, infectious prophylaxis, hepatitis C coinfection, metabolic complications, and malignancy are all discussed.

Characteristics of Patients on Antiretroviral Therapy With Prolonged Virological Failure

Characteristics of Patients on Antiretroviral Therapy With Prolonged Virological Failure

Antiretroviral Therapy in HIV/HCV Co-Infection Italian Consensus Workshop

About 50% of people living with the HIV infection in Italy are co-infected with HCV. In this group of patients, the primary cause of mortality is liver disease, which accounts for up to 14% of deaths. HIV/HCV co-infection also exposes patients to a higher risk of progression to AIDS, a faster evolution towards cirrhosis, more frequent drug toxicity, and lower tolerance for antiretroviral therapy. Moreover, HCV infection can play a part in increasing immune system depression; neurological, cognitive and renal damage; and bone fragility. Hence an optimal antiretroviral regimen needs to be chosen for co-administration with anti-HCV therapy and timed appropriately to improve the prognosis of co-infected HIV/HCV patients. Unfortunately, however, data on the safety and efficacy of antiretroviral drugs in these patients is scarce, as are studies of pharmacokinetics in patients with advanced liver impairment. Furthermore, restoring adequate immune constitution seems not to slow the progression of liver disease, and the metabolic and hepatic toxicity of some antiretroviral drugs can even contribute to inflammatory and fibrogenic processes. It is therefore essential that HIV/HCV co-infected patients receive only medications capable of ensuring the best immune recovery but possessing the lowest potential to trigger immune reconstitution syndrome or hepatic and metabolic damage.

Drug–Drug Interactions Between Antiretroviral and Immunosuppressive Agents in HIV-Infected Patients After Solid Organ Transplantation: A Review

Since the introduction of combination antiretroviral therapy (cART) resulting in the prolonged survival of HIV-infected patients, HIV infection is no longer considered to be a contraindication for solid organ transplantation (SOT). The combined management of antiretroviral and immunosuppressive therapy proved to be extremely challenging, as witnessed by high rates of allograft rejection and drug toxicity, but the profound drug-drug interactions between immunosuppressants and cART, especially protease inhibitors (PIs) also play an important role. Caution and frequent drug level monitoring of calcineurin inhibitors, such as tacrolimus are necessary when PIs are (re)introduced or withdrawn in HIV-infected recipients. Furthermore, the pharmacokinetics of glucocorticoids and mTOR inhibitors are seriously affected by PIs. With the introduction of integrase inhibitors, CCR5-antagonists and fusion inhibitors which cause significantly less pharmacokinetic interactions, have minor overlapping toxicity, and offer the advantage of pharmacodynamic synergy, it is time to revaluate what may be considered the optimal antiretroviral regimen in SOT recipients. In this review we provide a brief overview of the recent success of SOT in the HIV population, and an update on the pharmacokinetic and pharmacodynamic interactions between currently available cART and immunosuppressants in HIV-infected patients, who underwent SOT.

Human herpesvirus 8-associated neoplasms: the roles of viral replication and antiviral treatment.

In this review, we highlight the importance of human herpesvirus 8 (HHV-8) lytic replication and the potential for antiviral therapies to prevent or treat HHV-8-related neoplasms. Diseases caused by HHV-8 infection include Kaposi sarcoma, multicentric Castleman disease (MCD), and primary effusion lymphoma (PEL), which occur primarily in patients with HIV infection. Kaposi sarcoma is the most common AIDS-associated malignancy worldwide. MCD and PEL occur less commonly but, like Kaposi sarcoma, are associated with poor treatment outcomes. Like all herpesviruses, HHV-8 is capable of either latent or lytic infection of cells. Although HHV-8 infection of tumor cells is predominately latent, accumulating data point to the importance of both lytic phase viral gene products and production of infectious virus. Antiviral agents that target herpesvirus DNA synthesis, such as ganciclovir, inhibit HHV-8 lytic replication and can prevent Kaposi sarcoma. Several HIV protease inhibitors may interfere with tumor growth and angiogenesis, and one protease inhibitor, nelfinavir, directly inhibits HHV-8 replication in vitro. Controlled trials are indicated to determine the clinical utility of antiviral suppression of HHV-8 replication, and identify the optimal antiretroviral regimens, for the prevention and treatment of Kaposi sarcoma.

HIV infection in women: Do sex and gender matter?

At least half of all HIV infections occur in women. Most women are of childbearing potential; therefore, issues encompassing reproduction and mother-to-child transmission are critical in the management of this population. The efficacy of antiretroviral therapy (ART) is similar in men and women, although rates of adverse events or toxicity may be higher in women, which, in turn, may be related to higher antiretroviral drug levels documented in pharmacokinetic studies. A substantial proportion of women may not derive the benefit of highly active ART because nonsuppressive regimens are commonly used, especially in resource-limited settings, to decrease mother-to-child transmission. The likely emergence of resistant virus can have long-term sequelae for the mother, child, and other exposed individuals. Additional studies are needed of sex/gender-related issues including antiretroviral toxicities, pharmacokinetic profiles of approved and novel agents, ART strategies during pregnancy to minimize HIV resistance, and determination of optimal antiretroviral regimens for women.

Adherence-resistance relationships to combination HIV antiretroviral therapy

Early views on the relationship between adherence and resistance postulated a bell-shaped relationship that balanced selective drug pressure and improved viral suppression along a continuum of adherence. Although this conceptual relationship remains valid, recent data suggest that each regimen class may have different adherence-resistance relationships. These regimen-specific relationships are a function of the capacities of resistant virus to replicate at different levels of drug exposure, which are largely, but not entirely, determined by the impact of mutations on susceptibility of the virus and the impact of the mutations on the inherent ability of the virus to replicate efficiently. Specific patterns of adherence, such as treatment discontinuations, may influence adherence-resistance relationship to combination regimens comprised of medications with differing half-lives. Host genomics that alters antiretroviral drug distribution and metabolism may also impact adherence-resistance relationships. Optimal antiretroviral regimens should be constructed such that there is little overlap in the window of adherence that selects for antiretroviral drug resistance.

The nephrologist in the HAART era

The nephrologist in the HAART era

What is the optimal antiretroviral regimen for the prevention of perinatal HIV transmission?

OF PERINATAL HIV TRANSMISSION? AMANDA COTTER, LUNTHITA DUTHELY, VICTOR HUGO GONZALEZ QUINTERO, MARY JO O’SULLIVAN, University of Miami, Obstetrics and Gynecology, Miami, Florida, University of Miami, OB/GYN Research, Miami, Florida, University of Miami, Dept of Ob/ Gyn-MFM Division, Miami, Florida OBJECTIVE: To determine the optimal antiretroviral (ART) regimen for the prevention of perinatal transmission (PNT) of HIV in women who do not require ART for their own health. STUDY DESIGN: Using prospectively gathered data from our perinatal database, women diagnosed HIV positive prior to or during pregnancy with care at our prenatal clinic from 1999-2004 were identified. Inclusion criteria were women requiring ART only for prevention of PNT and neonatal HIV status. Women were categorized according to ART use in pregnancy: Trizivir, Combivir/Nevirapine (NVP), Combivir/Nelfinavir (NFV). RESULTS: The cohort comprised 634 deliveries of whom 155 women required ART only for prevention of PNT: Trizivir n = 61, Combivir/NVP n = 88, Combivir/NFV n = 6. A VL!1000 at delivery was achieved by 82% on Trizivir, 76% on Combivir/NVP and 83% on Combivir/NFV. The mean duration of therapy was 15.9, 15.3 and 20.9 weeks for Trizivir, Combivir/NVP and Combivir/NFV respectively.There was one case of hepatotoxicity associated each with Combivir/NVP and Combivir/NFV. All infants were liveborn except for 2 stillbirths and 2 spontaneous abortions in the Combivir/NVP group. There was only one case of PNT and this was in a woman on Trizivir. CONCLUSION: Although rarely utilized outside of pregnancy, Trizivir is an ideal ART regimen associated with similar pregnancy outcomes to other popular regimens without a significant risk of toxicity or adherence issues while reserving other ART regimens for later when required for maternal health.

Age at Which HIV Infection Can Be Detected in Infants

In St. Petersburg, Russia, we sought to describe the characteristics of active high-risk injection drug users (IDUs) to evaluate the associations between behavioral and demographic characteristics and HIV-1 infection and to describe 3 discrete recruitment methods. Active high-risk IDUs were recruited in 3 ways: through street outreach, at facilities serving IDUs, and by network-based chain referral. Recruits were screened, counseled, and tested for HIV-1. Sociodemographic and behavioral data were collected. HIV-1 prevalence was analyzed as a function of sociodemographic and behavioral variables. During the 10-month recruitment period, data from 900 participants were collected: median age was 24 years, and in the previous month, 96% used heroin and 75% shared needles with others. The baseline HIV prevalence was 30% (95% confidence interval [CI]: 27 to 33). Recruitment through social networks was the most productive strategy. HIV-positive individuals were younger, but none of the other sociodemographic or behavioral characteristics differed significantly by HIV status. The estimated HIV prevalence of 30% places St. Petersburg among the worst IDU-concentrated epidemics in Europe. Recruitment through network-based chain referral is a useful method for recruiting active IDUs. Sociodemographic and behavioral links to prevalent HIV infection remain to be elucidated.