Alvan Fisher

Hierarchical pattern of mucosal candida infections in HIV-seropositive women

PURPOSE Candida is the most common cause of opportunistic mucosal infections in human immunodeficiency virus (HIV)-positive women. We had observed an apparent correlation between the severity of immunodeficiency and the site of mucosal candida infection. The current study was designed to determine whether significant correlations existed between the sites of mucosal candida infection and the degree of immunodeficiency, as determined by subsets of lymphocyte populations. PATIENTS AND METHODS The subjects in this study are 66 HIV-seropositive women evaluated by members of the Brown University Acquired Immunodeficiency Syndrome (AIDS) Program during the 3-year period, September 1, 1986, through August 30, 1989. All patients had thorough clinical evaluations and relevant laboratory studies at defined intervals. All patients with CD4 lymphocyte counts below 0.2 X 10(9)/L received zidovudine therapy as soon as it became available. After July 1988, all patients with CD4 counts below 0.2 X 10(9)/L received prophylaxis against Pneumocystis carinii pneumonia. All patients were counseled about HIV infection, its modes of transmission, and the early symptoms of opportunistic infections. RESULTS The longitudinal data demonstrated that candida often infected vaginal mucosa when there was no significant reduction in CD4 lymphocyte counts. Candida infection of the oropharyngeal mucosa was associated with highly significant reductions in CD4 lymphocyte counts. Esophageal candidiasis occurred only with advanced immunodeficiency associated with CD4 counts below 0.1 X 10(9)/L. CONCLUSIONS Candida mucosal infections occur in a hierarchical pattern in women with HIV infection. Determination of the basis for the differences in susceptibility to candida of the vaginal, oropharyngeal, and esophageal mucosal surfaces will require further studies.

Human immunodeficiency virus infection in North American women: experience with 200 cases and a review of the literature.

This study was designed to define the epidemiology and natural history of human immunodeficiency virus (HIV) infection in women in Rhode Island. Two hundred women referred to Brown University physicians from 1986 through 1990 were evaluated at 3-to-6-month intervals for 12 to 60 months. All received antiretroviral therapy and prophylaxis against opportunistic infections when indicated on the basis of CD4 lymphocyte counts. Major findings included: 1) rapid shift of dominant mode of transmission from intravenous drug sharing to heterosexual route; 2) significant gender-specific differences in clinical presentation; 3) increased frequency of cervical dysplasia in women infected via intravenous needle sharing; 4) no definite gender-specific differences in progression of HIV infection; 5) enormous societal impact of HIV infection in women. Principal conclusions are: 1) rapid change to predominantly heterosexual HIV transmission can occur in North America, with serious societal impact; 2) gender-specific clinical features can lead to earlier diagnosis of HIV infection in women; 3) HIV infection in women does not pursue an inherently more rapid course than that observed in men.

Tenofovir DF plus lamivudine or emtricitabine for nonoccupational postexposure prophylaxis (NPEP) in a Boston Community Health Center.

Background:Nonoccupational postexposure prophylaxis (NPEP) has been used to decrease HIV transmission after high-risk exposures. However, suboptimal adherence in completing the recommended 28-day course has resulted in prophylaxis failures. Fenway Community Health, the largest center caring for HIV-infected and high-risk men who have sex with men (MSM) in New England, began an NPEP program in 1997, initially using zidovudine-based regimens. Methods:Two phase 4 studies, using tenofovir DF regimens combined with either lamivudine or emtricitabine, were conducted. This paper evaluates the experience of those who used tenofovir-based NPEP regimens, comparing the subjects to historical controls who used zidovudine-containing regimens. Results:Between May 2004 and March 2005, 44 individuals who presented after high-risk sexual exposure were prescribed tenofovir DF/lamivudine for NPEP. Between March 2005 and March 2006, 68 individuals with 72 high-risk experiences received tenofovir DF/emtricitabine, and were compared to122 historical controls who were prescribed 126 courses of zidovudine plus lamivudine between January 2000 and May 2004. Seventy-two percent of those who took tenofovir DF and emtricitabine, and 87.5% of the participants who took tenofovir DF and lamivudine, for NPEP completed their regimens as prescribed, whereas only 42.1% of those who took zidovudine plus lamivudine did so (P < 0.0001). Participants who took tenofovir DF-containing regimens were more likely to report diarrhea or abdominal discomfort; patients who took zidovudine-containing regimens were more likely to report nausea and vomiting, which was often severe enough to lead to product discontinuation. Conclusions:Tenofovir DF-containing regimens for NPEP are generally well tolerated with high completion rates. Tolerability and adherence compared favorably to zidovudine-containing regimens used previously. Tenofovir DF-containing regimens should be considered for PEP to enhance adherence and regimen completion.

Natural history of acquired immunodeficiency syndrome in women in rhode island

PURPOSE Current recommendations for treatment of human immunodeficiency virus (HIV) infection and for prophylaxis against associated opportunistic infections in North America are largely based on observations of HIV infection in males. In an effort to determine whether the natural history and clinical course may be different, with implications relevant to prophylaxis against opportunistic infections, we have documented the clinical courses of the first 24 known cases of acquired immunodeficiency syndrome (AIDS) in women in Rhode Island, most of whom developed Centers for Disease Control-defined AIDS before the availability of an effective antiviral agent (i.e., zidovudine) or a well-defined approach to prophylaxis against opportunistic infections (e.g., oral trimethoprimsulfa). PATIENTS AND METHODS The subjects in this study are 24 women with AIDS who were treated by members of the Brown University medical faculty from June 1982 through June 1988. All patients had thorough clinical evaluations and appropriate laboratory studies as they became available. All were followed at intervals no greater than two months. All opportunistic infections were treated by appropriate, specific antimicrobial therapy. When zidovudine became available, it was administered to all remaining patients in the study. All subjects were counseled about HIV infection, its modes of transmission, and the early symptoms of opportunistic infections. RESULTS These observations yielded the following three major findings: (1) Candida esophagitis was the most common (38%) AIDS-defining event; (2) Pneumocystis carinii pneumonia was less frequently the AIDS-defining event (13%) and occurred less commonly during the illness (29%) than in North American males with AIDS; (3) Of 14 women in whom the diagnosis of AIDS was established before January 1, 1987, the mean survival time after diagnosis was greater than 20 months. CONCLUSION More information on the natural history of HIV infection in North American women is urgently needed. If more extensive data from other geographic regions confirm the observations in this study, the optimal approach to prophylaxis against opportunistic infections in women with AIDS may be substantially different from that which is most appropriate for males.

HIV-positive women : reasons they are tested for HIV and their clinical characteristics on entry into the health care system

Study objective:To describe the reasons for the HIV testing of HIV-positive women and their clinical presentation and to make specific laboratory comparisons between women intravenous drug users (IVDUs) and non-IVDUs who were heterosexually infected (HTs).Design:Consecutive case series.Setting:Four primary care sites associated with the Brown University AIDS Program.Participants:140 consecutive HIV-seropositive women.Results:The most common reason for HIV testing in both groups was self-perception of risk. Presenting T-helper lymphocyte counts, leukocyte counts, and hematocrits did not differ significantly between the groups. Intravenous drug users were significantly more likely than HTs to have evidence of hepatitis B virus exposure (p<0.0001) and to report the history of a sexually transmitted disease (p=0.005). Twenty percent of HTs versus 10% of IVDUs were tested only after they had HIV-related symptoms. The most frequent clinical presentation for both groups was Centers for Disease Control Group IV/A constitutional symptoms.Conclusions:Many HIV-seropositive women do not enter the health care system until they are symptomatic, but those infected heterosexually and those using parenteral drugs have similar laboratory indices at presentation. AIDS education strategies toward all women at risk must include information about manifestations of HIV disease in women, as well as preventive measures, to ensure early access to the health care system.

Pharmacokinetic evaluation and short-term activity of stavudine, nevirapine, and nelfinavir therapy in HIV-1-infected adults.

Objective:Evaluate pharmacokinetic interaction, short-term safety, and antiretroviral activity of stavudine (d4T), nevirapine (NVP), and nelfinavir (NFV) as combination HIV-1 therapy. Design:Prospective, open-label study investigating the pharmacokinetic interactions between d4T, NVP, and NFV and documenting short-term tolerability and virologic and immunologic activity. Methods:Twenty-five HIV-1-infected adults, naive to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), ≤6 months of d4T treatment, CD4 ≥100 cells/mm3, and viral load ≥5,000 copies/mL enrolled. All received NFV 750 mg 3 times daily and d4T 30–40 mg twice daily for 1 week, then added NVP at 200 mg once daily for 2 weeks and 200 mg twice daily thereafter. Steady-state pharmacokinetic parameters of NFV, AG1402 (metabolite of NFV), and d4T were compared before and after the addition of NVP. Results:No statistically significant changes in NFV or d4T pharmacokinetics were observed following the addition of NVP. Levels of AG1402 were suppressed 60–70%. Drug-related adverse events were seen at expected rates. At day 36, median viral load suppression was 2.0 log10 and absolute CD4 count increased by 111 cells/mm3. Conclusions:NVP administration did not significantly affect the steady-state pharmacokinetic parameters of NFV or d4T. The combination of d4T, NVP, and NFV induced rapid suppression of HIV-1 viral load and rises in CD4 cell count.