Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication persists in such patients is unknown. HIV-1 cDNA episomes are labile products of virus infection and indicative of recent infection events. Using episome-specific PCR, we demonstrate here ongoing virus replication in a large percentage of infected individuals on highly active anti-retroviral therapy, despite sustained undetectable levels of plasma viral RNA. The presence of a reservoir of 'covert' virus replication in patients on highly active anti-retroviral therapy has important implications for the clinical management of HIV-1-infected individuals and for the development of virus eradication strategies.
1 reported that among 221 women who were attempting to become pregnant, conception occurred only during a six-day period that ended on the day of ovulation. This study provides excellent information for women who are trying to conceive. However, these data are probably not applicable to the large number of women who are trying to avoid pregnancy or having unprotected intercourse but who do not want to become pregnant. These women are much more likely to have intercourse outside the six-day fertile period and thus are more likely to conceive outside that period.In order to determine the probability that intercourse on any day outside the six-day interval can result in pregnancy, it is necessary to examine menstrual cycles in which intercourse did not occur during those six days. Wilcox et al. reported that 31 of 625 menstrual cycles, or 5 percent, met this definition, and none resulted in conception. Indeed, they stated that they could not "exclude a probability of conception of up to 12 percent on either the seventh day before ovulation or the day after ovulation (95 percent confidence interval, 0 to 0.12)." We question whether their data are sufficient to exclude the possibility that conception may occur over a much broader range of days surrounding ovulation. It would be helpful to know how many women are represented by these 31 cycles and if and when intercourse occurred during each cycle. The power of these data to determine whether intercourse after ovulation can result in pregnancy is likely to be low.Since approximately 50 percent of the pregnancies in the United States are not planned and since a large number of women may use the timing of ovulation to make decisions about contraception, it is important to obtain more accurate information about the likelihood of conceiving during each day of the menstrual cycle. Such information can best be obtained by studying a population-based cohort of women and examining a larger number of menstrual cycles in which intercourse did not occur during the six-day interval identified by Wilcox et al. DD. Timing of sexual intercourse in relation to ovulation -effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med 1995;333:1517-21. Instructions for Letters to the EditorLetters to the Editor are considered for publication (subject to editing and abridgment) provided they do not contain material that has been submitted or published elsewhere. Please note the following:• Your letter must be typewritten and triple-spaced. • Its text, not including references, must not exceed 400 words (please include a word count). • It must have no more than five references and one figure or table.• It should not be signed by more than three authors. • Letters referring to a recent Journal article must be received within four weeks of its publication. • Please include your full address, telephone number, and fax number (if you have one). Our fax numbers: 617-739-9864 and 617-734-4457Our e-mail address: letters@edit.nejm.orgWe cannot acknowledge r...
Few modern diseases have experienced as rapid and dramatic change in prognosis and treatment as HIV infection. The introduction of active antiretroviral therapy (ART) and effective prophylaxis of opportunistic infections ushered in a new era in the treatment of HIV infection and changed dramatically the natural history of this disease. The rates of admission to the intensive care unit (ICU) and intensive care mortality in patients with HIV infection have shifted repeatedly during the AIDS epidemic, influenced by attitudes of patients and providers toward utility of care. In the ART era, patients with HIV infection admitted to the ICU fall into 3 general categories: those with AIDS-related opportunistic infections, those who are experiencing complications related to ART, and those with medical problems unrelated to HIV infection. In this article, the authors provide a review of the most common life-threatening complications in patients with HIV infection.
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