Antiretroviral Drug Use Research Articles

Resistance to antiretroviral treatment in Gabon: need for implementation of guidelines on antiretroviral therapy use and HIV-1 drug resistance monitoring in developing countries.

The protease and reverse transcriptase (RT) genes were studied in antiretroviral (ARV)-experienced and drug-naive HIV-1-infected individuals in Libreville, Gabon. We have shown, although on a limited number of samples that in 58% (11/19) of the patients, with a mean of 17.7 months of ARV drug experience, major mutations inevitably inducing resistances to ARV drugs were present. Resistance was mainly observed to the NRTIs (nucleoside analogue RT inhibitors). This high prevalence may reflect inappropriate ARV drug use. In order to avoid the rapid emergence of resistant viruses on a large scale in the developing world, it is important that the infrastructures necessary to monitor ARV treatment are also rapidly implemented in these countries and that clinicans are trained in the appropriate use of ARV drugs. A continuous surveillance of the circulation of ARV drug-resistant viruses must be organized to guide ARV treatment strategies and policies.

Resistance to Antiretroviral Treatment in Gabon: Need for Implementation of Guidelines on Antiretroviral Therapy Use and HIV-1 Drug Resistance Monitoring in Developing Countries

The protease and reverse transcriptase (RT) genes were studied in antiretroviral (ARV)-experienced and drug-naive HIV-1-infected individuals in Libreville, Gabon. We have shown, although on a limited number of samples that in 58% (11/19) of the patients, with a mean of 17.7 months of ARV drug experience, major mutations inevitably inducing resistances to ARV drugs were present. Resistance was mainly observed to the NRTIs (nucleoside analogue RT inhibitors). This high prevalence may reflect inappropriate ARV drug use. In order to avoid the rapid emergence of resistant viruses on a large scale in the developing world, it is important that the infrastructures necessary to monitor ARV treatment are also rapidly implemented in these countries and that clinicans are trained in the appropriate use of ARV drugs. A continuous surveillance of the circulation of ARV drug-resistant viruses must be organized to guide ARV treatment strategies and policies.

Use of a stochastic model to develop understanding of the impact of different patterns of antiretroviral drug use on resistance development.

To use a stochastic model to gain insights into the consequence for resistance development of different drug use patterns. We consider use of three drugs (A, B and C) where for each drug one and only one viral mutation is associated with ability to replicate (effective reproductive ratio, R > 1) in the presence of that drug as monotherapy. For drug A mutation is a, etc. We define eight populations of short-lived infected cells that live 1 day: Vo with no mutations a, b, c; Va with mutation a only, Vab with mutations a and b, etc. A random number generator was used to determine whether mutations occur in any one round of replication and to sample from a Poisson distribution to determine for each cell the number of cells of the same population created in the next generation, using the R operative at that time. Values of R depended on drug exposure, cost of resistance and availability of target cells. Treatment strategies and the resulting percentage (over 100 runs) developing full "resistance" in 1500 days (Vabc not equal 0) were: (i) ABC 1500 days 0%; (ii) A 300 days, AB 300 days, ABC 900 days 100%; (iii) AB 300 days, ABC 1200 days 33%; (iv) ABC 2/3 1500 days 15%; (v) ABC 1/2 1500 days 100%; (vi) ABC 50 days, no drugs 50 days, for 1500 days 1%, where ABC 2/3 means on-drug for 2 days in every 3, ABC 1/2 represents on-drug for 1 day in every 2, and represents suboptimal adherence. This model helps to develop understanding of key principles concerning development of resistance under different patterns of treatment use.

HIV infection in women in the United States: status at the Millennium.

During the past decade, knowledge of human immunodeficiency virus (HIV) infection in women has expanded considerably but may not be easily accessible for use in understanding and prioritizing the clinical needs of HIV-infected women. To perform a comprehensive review of epidemiologic, clinical, psychosocial, and behavioral information about HIV in women, and to recommend an agenda for future activities. A computerized search, using MEDLINE and AIDSline, of published literature was conducted; journal articles from January 1981 through July 2000 and scientific conference presentations from January 1999 through July 2000 were retrieved and reviewed for content; article reference lists were used to identify additional articles and presentations of interest. Data from surveillance and prospective cohort studies with at least 20 HIV-infected women and appropriate comparison groups were preferentially included. Included studies of historical importance and subsequent refined analyses of topics covered therein; these and studies with more current data were given preference. Four studies involving fewer than 20 women were included; 2 studies were of men only. Women account for an increasing percentage of all acquired immunodeficiency syndrome (AIDS) cases, from 6.7% (1819/27 140 cases) in 1986 to 18% (119 810/724 656 cases) in 1999. By the end of 1998, of all newly reported AIDS cases among women, proportionally more were in the South (41%), among black women (61%), and from heterosexual transmission (38%). Of note, increasingly more women have no identified or reported risk, about half or more of whom are estimated to be infected heterosexually. It is estimated that a total of at least 54% of women newly reported with AIDS in 1998 acquired HIV through heterosexual sex, including women in the no identified or reported risk category estimated to have been infected heterosexually, meeting the surveillance heterosexual risk definition. Natural history, progression, survival, and HIV-associated illnesses-except for those of the reproductive tract-thus far appear to be similar in HIV-infected women and men. Although antiretroviral therapy has proven to be highly effective in improving HIV-related morbidity and mortality rates, women may be less likely than men to use these therapies. Drug use, high-risk sex behaviors, depression, and unmet social needs interfere with women's use of available HIV prevention and treatment resources. Continued research on HIV pathogenesis and treatment is needed; however, emphasis should also be placed on using existing knowledge to improve the clinical care of women by enhancing use of available services and including greater use of antiretroviral therapy options, treating depression and drug use, facilitating educational efforts, and providing social support for HIV-infected women.

Thrombocytopenia in HIV-infected drug users in the HAART era

The present case-control study compared 26 HIV+ drug users having persistent thrombocytopenia (TCP<150 000/mm 3 ) with 54 available age, gender and HIV CDC classification matched controls with normal platelet counts. Participants were followed longitudinally over a 2-year period (1998-2000), and hematological alterations evaluated in relationship to antiretroviral treatment, drug use and nutritional (selenium) status. Demographic information and medical history, including antiretroviral treatment were obtained. Blood was drawn for complete cell blood count, T lymphocytes and viral load. Sixty-nine percent of the individuals with persistent TCP and 49% of the controls were receiving antiretrovirals. At baseline, no significant differences in CD4 existed between the two groups. Over time, CD4 cell count declined in the cases ( P = 0.05) and a significantly higher proportion of the cases (38%) developed AIDS (CD4<200 cell/mm 3 ), as compared to the controls (18%, P = 0.004). A high risk for development of thrombocytopenia was observed with specific drug use (heroin 2.96 times, P = 0.0007), selenium levels below 145 w g/l (6 times, P = 0.008), and abnormal liver enzyme (SGOT) levels (2 times, P = 0.002). Together, these results indicate a number of factors that may be sensitive predictors of thrombocytopenia, which, despite antiretroviral treatment, appears to be related to more rapid disease progression in drug users.

The relationship of psychological variables and disease progression among long-term HIV-infected men.

This study investigated the contribution of psychological factors to disease progression among long-term HIV-1 infected gay men. Participants completed self-report measures including coping strategies, life events, social support, personality and psychological morbidity and were followed clinically for up to 30 months. Cox proportional hazards survival analyses were carried out to CD4<200 x 106/1 and AIDS-related complex (ARC) or AIDS diagnosis controlling for viral load, antiretroviral drug use and CD4 count. Only acceptance coping was a significant predictor of time to ARC or AIDS diagnosis: the risk of ARC or AIDS was almost 5 times greater for those scoring within the lowest tertile compared with those scoring in the highest tertile (HR=4.7, 95% CI 1.8-12.3).

CDC alters recommendations on rifamycin–antiretroviral drug use

CDC alters recommendations on rifamycin–antiretroviral drug use

PREVENTION OF HIV INFECTION IN CHILDREN

The threshold of a new century is an opportune time to review advances in the prevention of HIV infection in children. In the United States, progress in the ability to virtually eliminate perinatal HIV transmission that was unthinkable just a few years ago has been achieved. Clinicians providing care to pregnant women should educate and counsel women about HIV and strongly recommend that they be tested. They should also counsel HIV-infected women about the means available to substantially decrease the risk for HIV transmission to their infants (e.g., antiretroviral drug use, avoidance of breast-feeding, elective C-section, encouraging pregnant women to use barrier methods during sexual intercourse, and to discontinue injection drug use). This article has highlighted some of the remaining challenges that constitute barriers to achieving maximal decrease of HIV infection in children. Studies conducted in resource-poor countries have added greatly to the understanding of vertical transmission of HIV, and they are now leading to practical and affordable approaches to reduce vertical HIV transmission world-wide. The results of this research must lead to coordinated public health action and a global political commitment to extend the benefits of antiretroviral drug prophylaxis that now exist widely in the United States to more resource-poor countries.

Utilization of prescribed drugs by HIV infected individuals: qualitative approach

The assessment, in its qualitative dimension, of the utilization--by HIV infected individuals--of selected prescribed drugs during the process of the search for and the obtaining of care in public health services in Belo Horizonte, Brazil. Fifty two semi-structured interviews with patients, health care workers and non-governamental organizations volunteers were carried out and 1,079 medical records were reviewed. Data were obtained on the utilization of prescribed drugs by HIV infected individuals, whose first visit to one of the public services studied occurred between January 1989 and December 1992. Problems related to the use of anti-retroviral and/or opportunistic infection medication were identified and a qualitative description of their possible causes and consequences was commented on. Refusal to use, difficulty in obtaining and in complying with the prescription were the main problems related to anti-retroviral drug use. Causes for such problems included: fear or occurrence of side effects, large number of daily capsules/pills, insufficient and/or irregular distribution of drugs by the public health services and the high cost of anti-retroviral therapy. Based on the reports, the main consequences are likely to be no or late use of anti-retroviral drugs, an increase in resistance and a worsening of the clinical course of the infection. Other problems identified were: self-medication, difficulty in obtaining medications for associated pathologies and in complying with sulfa prescription. A better understanding of the main obstacles and difficulties experienced by the user of the services, from the moment of the prescription and throughout the treatment, may contribute to an improvement in compliance and the availability and adequate distribution of drugs.

New strategies for the management of AIDS-related CMV retinitis in the era of potent antiretroviral therapy

The management of AIDS-related cytomegalovirus (CMV) retinitis is evolving because of newly available anti-CMV drugs and because of the effect of potent antiretroviral therapy. New management issues are related to the improved immune function that occurs with antiretroviral drug use and to associated increases in patient survival. Patients can be categorized on the basis of their history of exposure to antiretroviral drugs and to their immune status; these factors will influence choices between treatment options. In some patients with improved immune function, specific anti-CMV therapy can be withdrawn altogether without reactivation of infection. There are curently many treatment options available for those who need specific anti-CMV treatment: ganciclovir via various routes (intravenous (IV), oral, intraocular implant); IV foscarnet; IV cidofovir; intravitreous fomivirsen; or a combination of these agents. Previous short-term therapies are being adapted to the long-term management of what has become a chronic disease. Management strategies also involve appropriate monitoring for the recurrence of disease activity and the development of complications, such as retinal detachment or immune recovery uveitis. This chapter provides an overview of new treatment strategies that will assist clinicians in choosing between treatment options.

Antiretroviral uptake in Australia: medical, attitudinal and cultural correlates.

The objective of this study was to describe the medical, attitudinal and cultural correlates of antiretroviral uptake amongst people living with HIV/AIDS (PLWHA) in Australia. Stratified purposive sampling produced a sample of 925 PLWHA, which represents 8.3% of the current population of PLWHA in Australia. Respondents completed a self-administered questionnaire which revealed that 78% of respondents were using antiretroviral drugs for HIV/AIDS. Logistic regression revealed that PLWHA were more likely to use antiretroviral drugs if they had more favourable attitudes toward antiretroviral drugs, if they had been diagnosed with an AIDS-defining illness, and if they had ever had a CD4/T-cell count below 400 copies/ml blood. Women were less likely than men to use antiretroviral drugs, and logistic regression revealed different predictors of antiretroviral drug use amongst men and women. Given the importance of attitudes toward antiretroviral drugs, it is likely that if the current confidence in antiretroviral drugs were to change, this would be reflected in an equally rapid cessation of treatment amongst many PLWHA.