Review of Screening Guidelines for Non-AIDS-Defining Malignancies: Evolving Issues in the Era of Highly Active Antiretroviral Therapy.

Review of Screening Guidelines for Non-AIDS-Defining Malignancies: Evolving Issues in the Era of Highly Active Antiretroviral Therapy.

AIDS Rev. 2012 Jan;14(1):3-16

Authors: Tyerman Z, Aboulafia DM

Abstract

HIV-associated morbidity and mortality have declined dramatically in the era of HAART. Through direct and indirect benefits of HAART, people with HIV/AIDS are living longer, developing less AIDS-defining cancers and more cancers commonly seen in the seronegative population. Herein, we review cancer screening strategies for people living with HIV and compare and contrast them with those of the general population. The most noticeable differences occur in anal and cervical cancer screening. Although anal cancer is uncommon in the general population, it is more prevalent in men who have sex with men and people at high risk for human papillomavirus infection, especially those infected with HIV. To address this, we recommend that a digital rectal exam and a visual inspection be performed annually. In addition, an anal Pap test should be performed soon after the diagnosis of HIV infection, with follow-up testing every six months until two normal tests. Abnormal cytological results are then investigated with high-resolution anoscopy and biopsy of suspicious lesions. In screening for cervical cancer, a Pap test should be performed during the anogenital exam after initial HIV diagnosis, with a second Pap six months later, then annually if the results are normal. A colposcopy should follow an abnormal result. Human papillomavirus testing as a screening method for cervical cancer in women with HIV can also be efficacious. In lung cancer screening, preliminary data suggest that low-dose computerized tomography may play an important role, but further research is needed. Screening for breast and colon cancer should follow guidelines for the general population. Early screening for prostate cancer based on a diagnosis of HIV lacks clear benefit.

PMID: 22297500 [PubMed - in process]

 

Temporal Changes in the Epidemiology of Transmission of Drug-Resistant HIV-1 across the World.

Temporal Changes in the Epidemiology of Transmission of Drug-Resistant HIV-1 across the World.

AIDS Rev. 2012 Jan;14(1):17-27

Authors: Frentz D, Boucher CA, van de Vijver DA

Abstract

A substantial number of studies have been performed across the world to determine transmitted drug resistance. Large variations between different parts of the world can be expected because of differences in availability over time of treatment. Time trend analyses are often not possible because of small numbers of included patients. In this review, we present the available data on the transmission of drug-resistant HIV, with a major emphasis on the time trends of drug resistance prevalences. We identified relevant literature by searching in PubMed through September 2009. Studies were grouped, according to the year of data collection, into the following time periods: < 2001, 2001-2003, > 2003. We selected a total of 215 studies, which included 43,170 patients. The following prevalences of transmission of drug-resistant HIV were found, in rank order: North America (12.9%), Europe (10.9%), Latin America (6.3%), Africa (4.7%), and Asia (4.2%). Changes over time in particular drugs classes were found in all parts of the world. Nucleoside reverse transcriptase inhibitor resistance declined over time in North America (p = 0.03), Europe (p < 0.001), and Latin America (p < 0.001). The decline in nucleoside reverse transcriptase inhibitor resistance reflects the improvement of treatment regimens in resource-rich settings. In contrast the resistance prevalence increased in Asia (p = 0.047) and Africa (p < 0.001). This can be explained by the antiretrovirals becoming more available during recent years in these continents. Nonnucleoside reverse transcriptase inhibitor resistance rose over time in North America (p < 0.001), Europe (p < 0.001), Latin America (p < 0.001), and Asia (p = 0.01). This paper gives a complete overview of the epidemiology of resistance of antiretroviral drugs in drug-naive patients worldwide. The time trends that were observed seem to reflect changes in describing prescriptions over time. Changes include the more wide-spread use of antiretroviral drugs in developing countries and the development of therapies from low-active mono-therapies to highly active antiretroviral regimens in the industrialized countries.

PMID: 22297501 [PubMed - in process]

 



HIV‑1 Molecular Epidemiology in the Balkans – A Melting Pot for High Genetic Diversity.

HIV‑1 Molecular Epidemiology in the Balkans – A Melting Pot for High Genetic Diversity.

AIDS Rev. 2012 Jan;14(1):28-36

Authors: Stanojevic M, Alexiev I, Beshkov D, Gökengin D, Mezei M, Minarovits J, Otelea D, Paraschiv S, Poljak M, Zidovec-Lepej S, Paraskevis D

Abstract

The Balkans is a gateway between Europe, Asia, and the African continent, a fact with potential important consequences on the epidemiology of HIV‑1 infection in the region. The duration of the HIV‑1 epidemics in many countries of the Balkans is similar to the one in the Western European countries. However, striking differences exist in several countries of the region in both the epidemic situation and, even more so, in our knowledge about it. In particular, the molecular epidemiology of HIV in the Balkans is largely unknown. In order to gain some preliminary insight into HIV‑1 diversity in the region, we reviewed the available molecular epidemiology data about HIV‑1 diversity in 10 countries of the region: Albania, Bulgaria, Croatia, Greece, Montenegro, Romania, Slovenia, Serbia, Turkey, and Hungary, a neighboring country to four Balkan countries. The data were obtained either from published studies or in direct communication with the participating members. The existing molecular epidemiology data revealed a broad diversity in subtype distribution among Balkan countries. In several countries, subtype B is predominant (e.g. Serbia, Slovenia, and Hungary), while in others the proportion of non‑B subtypes is much larger (Albania subtype A, Romania subtype F). In some areas, HIV‑1 subtype distribution is marked by divergence between different risk groups or transmission routes (e.g. Croatia). Recently, HIV‑1/AIDS epidemics in Eastern Europe have been among the fastest growing in the world. Many major contributing factors for the breakout and spread of these epidemics are present in many of the Balkan countries, as reflected through the process of social transition, wars, unemployment, extensive drug use, high sexual risk behavior, as well as other factors. Yet, in the Balkan countries the prevalence rate of HIV‑1 infection is low, under 0.1 percent. Concomitantly, the molecular epidemiology of HIV‑1 in the Balkans has not been thoroughly studied so far. The review and analysis of the available data indicate a broad diversity of circulating HIV‑1 subtypes in the region, with the predominance of non‑B clades in some countries, underscoring the need for an ongoing surveillance of HIV‑1 diversity. The setup of a collaborative network might provide important information for the better management and control of the HIV‑1 epidemic in the area.

PMID: 22297502 [PubMed - in process]

 

Renal Complications in HIV Disease: Between Present and Future.

Renal Complications in HIV Disease: Between Present and Future.

AIDS Rev. 2012 Jan;14(1):37-53

Authors: Maggi P, Bartolozzi D, Bonfanti P, Calza L, Cherubini C, Di Biagio A, Marcotullio S, Montella F, Montinaro V, Mussini C, Narciso P, Rusconi S, Vescini F

Abstract

The recent introduction of new antiretroviral drugs, characterized by high efficiency and improved safety profiles, has not reduced the incidence of long-term adverse effects, in some cases manifested as selective organ damage. The presence of organ damage in patients receiving antiretroviral treatment is not only the expression of treatment toxicity, but also a complex interaction between individual risk factors, HIV-correlated effects, and antiretroviral drug toxicity. Kidney damage belongs to these adverse events. Renal function abnormalities are present in a large percentage of patients with HIV infection. Moreover, HIV-associated renal disease seems to be associated with progression to AIDS and death. In this review we address the various aspects of the epidemiology of renal damage, the interaction and the convergent effect of HIV and antiretroviral drugs in the onset of kidney injury, the interplay between kidney function and other organ systems, early clinical management, the monitoring of renal function, and a proposal of clinical approach to kidney disease in daily practice. Finally, we discuss future perspectives of renal damage in HIV patients and evaluate the patient’s perspective.

PMID: 22297503 [PubMed - in process]

 

Antiretroviral Drugs for Pre-Exposure Prophylaxis of HIV Infection.

Antiretroviral Drugs for Pre-Exposure Prophylaxis of HIV Infection.

AIDS Rev. 2012 Jan;14(1):54-61

Authors: Fernández-Montero JV, Barreiro P, Del Romero J, Soriano V

Abstract

Though a large number of antiretrovirals have been developed for the treatment of HIV infection, new HIV infections continue to occur, especially among certain high-risk groups, such as men who have sex with men. Overall, the current estimated incidence of HIV infection is 2.5-fold higher than the number of individuals that begin antiretroviral therapy every year worldwide. Along with the personal drama caused by the diagnosis of HIV infection, other considerations in society, including economics and interpersonal relationships, make the need for HIV prevention strategies a priority. Though vaccines have shown great efficacy in the combat of other epidemics, currently there is no effective vaccine against HIV, and it is unlikely that any will become available in the near future. Thus, new approaches such as pre-exposure prophylaxis are viewed with increasing interest. The results from recent clinical trials have provided support in favor of distinct pre-exposure prophylaxis modalities. However, concerns exist about increasing risky behaviors and selection and spread of antiretroviral drug resistance with a broader use of pre-exposure prophylaxis. The aim of this review is to examine the evidence available on the effectiveness of pre-exposure prophylaxis and its potential influence on the HIV epidemics.

PMID: 22297504 [PubMed - in process]

 



State of the Art in Intravaginal Ring Technology for Topical Prophylaxis of HIV Infection.

State of the Art in Intravaginal Ring Technology for Topical Prophylaxis of HIV Infection.

AIDS Rev. 2012 Jan;14(1):62-77

Authors: Kiser PF, Johnson TJ, Clark JT

Abstract

There is renewed interest in the development of long-term, controlled-release dosage forms for the intravaginal delivery of antiretrovirals for HIV prophylaxis. This interest has catalyzed a renaissance in vaginal drug delivery, increasing the fundamental understanding of determinants of controlled drug delivery in the vagina as well as development of new materials, delivery platforms, and animal models. Our goal in writing this review from the perspective of engineers and pharmaceutical scientists interested in prevention of sexually transmitted infections is to highlight the current state of the art, progress in preclinical programs, new drug-delivery device designs, and to discuss some of the important unknowns in this area of HIV prevention for the general audience involved in HIV research. As far as antiretrovirals are concerned, this review is limited to programs working with antiretrovirals that are supported with an investigational new drug filing. We draw primarily from published papers in the PubMed and CAS databases, however, many of the most recent advances have yet to appear in the peer-reviewed literature and for this class of publications we draw from a recent formulation workshop held by CONRAD as well as from the Microbicides, Controlled Release Society, and CROI meetings.

PMID: 22297505 [PubMed - in process]

 

Current Treatment Strategies, Complications and Considerations for the Use of HIV Antiretroviral Therapy during Pregnancy.

Current Treatment Strategies, Complications and Considerations for the Use of HIV Antiretroviral Therapy during Pregnancy.

AIDS Rev. 2011 Oct;13(4):198-213

Authors: Senise JF, Castelo A, Martínez M

Abstract

The global prevalence of HIV infection in the female population presents a significant healthcare burden in terms of mother-to-child transmission (MTCT) of the disease. This review aims to discuss current trends and treatment guidelines for the use of antiretroviral therapy during pregnancy and associated complications in this population. Historically, antiretroviral monotherapy with zidovudine was commonly used for preventing MTCT, and monotherapy with single-dose nevirapine is still used for prevention in resource-limited settings. Evidence suggests that combination therapy with HAART is a more effective treatment option than monotherapy when managing HIV in pregnant women. Current treatment guidelines recommend the use of HAART with a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTI) as first-line therapy for the management of HIV infection in pregnant women and for preventing MTCT. Complications associated with the use of antiretroviral therapy during pregnancy should be taken into consideration when selecting a new antiretroviral regimen, or when continuing certain antiretroviral regimens in HIV-infected women who become pregnant while on therapy. NNRTI have been associated with severe and sometimes fatal hepatoxicity in some pregnant women and potentially teratogenic side effects in the fetus, and their use raises concerns regarding the development of drug- and class-resistant mutations. PI-based HAART has been associated with an increased risk of adverse effects such as premature delivery, low birth weight, dyslipidemia, glucose intolerance, and lipodystrophy. Despite this, initiating antiretroviral therapy with a PI plus two NRTI may become the preferred treatment option in pregnant women. Many of the side effects associated with PI were more prevalent when older PI and PI-based regimens that included those in combination with thymidine analog NRTI were used. An individual’s history and baseline clinical and laboratory parameters should also be taken into consideration when choosing the most appropriate antiretroviral regimen during pregnancy.

PMID: 21975356 [PubMed - in process]

 

HIV Drug Resistance Assessment in the Western Pacific Region. A Systematic Review.

HIV Drug Resistance Assessment in the Western Pacific Region. A Systematic Review.

AIDS Rev. 2011 Oct;13(4):214-26

Authors: Yu D, Sutherland D, Ghidinelli M, Jordan MR

Abstract

Antiretroviral therapy is being rapidly scaled-up in Western Pacific region countries. Prevention and assessment of HIV drug resistance is an essential component of successful global antiretroviral therapy scale-up. We performed a systematic review of public health surveys and HIV drug resistance studies conducted in the low- and middle-income countries in the Western Pacific region. A total of 38 publications assessing HIV drug resistance were reviewed. Studies assessing transmitted drug resistance in recently infected individuals or drug resistance among individuals starting antiretroviral therapy found low rates of HIV drug resistance. Assessments of HIV drug resistance emerging in populations receiving antiretroviral therapy demonstrated variable rates of drug resistance, but suggest an urgent need to support antiretroviral therapy adherence and retention in care, ensure the use of quality assured drugs, and guarantee continuous drug supplies. Additionally, programmatic assessment informed by routine standardized surveillance of transmitted and acquired HIV drug resistance is essential to optimize antiretroviral therapy delivery in the Western Pacific region.

PMID: 21975357 [PubMed - in process]

 

Protease Inhibitors as Preferred Initial Regimen for Antiretroviral-Naive HIV Patients.

Protease Inhibitors as Preferred Initial Regimen for Antiretroviral-Naive HIV Patients.

AIDS Rev. 2011 Oct;13(4):227-33

Authors: Tejerina F, López Bernaldo de Quirós JC

Abstract

At present, the majority of patients who have initiated their first antiretroviral therapy have received a combination comprising a nonnucleoside and two nucleoside analogues. The use of nonnucleosides as first-line therapy has been favored for their more convenient dosing, with less pill numbers, and the possibility of co-formulation with nucleoside analogues. Although protease inhibitors are also considered to be a preferred standard, they have been less frequently used as first regimen of choice because of their adverse effects in the short to medium term. The introduction of darunavir and atazanavir as new protease inhibitors boosted with ritonavir has resulted in a significant change in this area. These drugs show a lower incidence of adverse effects, allow once-a-day administration, and have a high barrier to resistance that prevents the selection of resistance mutations in case of virologic failure. On this basis, it is likely that over the next few years these drugs will become a standard of care, gaining acceptance and being used more frequently as preferred first-line regimen.

PMID: 21975358 [PubMed - in process]

 

Evolutionary mechanisms of retroviral persistence.

Evolutionary mechanisms of retroviral persistence.

AIDS Rev. 2011 Oct;13(4):234-9

Authors: Whitney JB, Lim SY, Wainberg MA

Abstract

Retroviruses are known to exhibit remarkable genomic pliancy, a capacity that has been attributed to one or more error prone steps in the viral replication cycle. However, increasing evidence suggests that such error represents a key element in viral survival, as exemplified by studies on virus immune evasion, shifts of cellular tropism, and anatomic compartmentalization, which facilitate persistent virus reservoirs. Understanding the dynamic mechanisms that contribute to the establishment and maintenance of retroviral persistence is critical toward the goal of attaining HIV-1 eradication.

PMID: 21975359 [PubMed - in process]