Effect on normal vaginal flora of three intravaginal microbicidal agents potentially active against human immunodeficiency virus type 1.

The effect on normal vaginal flora of three intravaginal microbicides potentially active against human immunodeficiency virus type 1 was examined. Volunteers received dextrin sulfate (D2S), nonoxynol-9 (N-9), or docusate sodium in separate placebo-controlled studies. High vaginal swabs were obtained for bacterial culture before and after microbicide application. D2S did not affect the vaginal flora. However, lactobacilli decreased by > or = 10(2) cfu/mL in 9 (56%) of 16 women given N-9 and in 5 (63%) of 8 women given docusate sodium. Women using N-9 were also significantly more likely to become colonized abnormally (usually with aerobic gram-negative rods) than were those using placebo, as were women using docusate sodium. Women with reduced lactobacilli were less likely to regain normal flora than were those whose lactobacilli were unaffected. However, coliform colonization occurred whether lactobacilli produced H2O2 or not. Continuous use of N-9 could induce susceptibility to urinary and gynecological infection. It is essential that potential microbicides are examined for activity against normal vaginal flora.

Safety study of nonoxynol-9 as a vaginal microbicide: evidence of adverse effects.

Nonoxynol-9 (N-9) is virucidal in vitro, and is therefore a candidate microbicide for preventing sexual transmission of HIV. However, the activity of N-9 is nonspecific, suggesting that virucidal levels may produce adverse effects including epithelial disruption, inflammation of the genital mucosa, or both. A randomized placebo controlled trial of daily use of 100 mg of N-9 took place for 1 week in 40 female volunteers. Outcome measures included symptoms, colposcopic and histologic changes in the genital tract, and impact on vaginal flora. Genital irritation was reported by 10 of the N-9 and 5 of the placebo group. Colposcopy showed erythema in 9 of the N-9 group and 2 of the placebo group. Histologic inflammation was found in 7 of the N-9 group and 2 of the placebo group. Inflammatory changes were characterized by patchy infiltration of the lamina propria predominantly with CD8+ lymphocytes and macrophages, in the absence of epithelial disruption. A transient reduction in numbers of lactobacilli was observed in 9 of the 15 women using N-9, and 6 of 18 women using placebo. N-9 used for 7 days in a standard spermicidal dose was associated with increased irritation, colposcopic and histologic evidence of inflammation and was more frequently associated with reduction in numbers of lactobacilli during gel use. The clinical significance of the recruitment of cells susceptible to HIV infection to the genital mucosa is unknown but raises concerns about the suitability of N-9 as a microbicide when given in this dose.

PIP: Since nonoxynol-9 (N-9) is virucidal in vitro, it is a candidate microbicide for preventing the sexual transmission of HIV. A randomized placebo-controlled trial of the daily use of 100 mg of N-9 was conducted for 1 week among 40 female volunteers aged 18-45 years. Genital irritation was reported by 10 of the N-9 users and 5 women in the placebo group. Colposcopy showed erythema in 9 of the N-9 group and 2 of the placebo group. Histologic inflammation was found in 7 of the N-9 group and 2 of the placebo group. Inflammatory changes in the women were characterized by patchy infiltration of the lamina propria mainly with CD8 lymphocytes and macrophages, in the absence of epithelial disruption. A transient reduction in the number of lactobacilli was observed in 9 of the 15 women using N-9, and 6 of the 18 women using placebo. N-9 used for 7 days in this standard spermicidal dose in the absence of sexual intercourse was therefore associated with increased irritation, colposcopic and histologic evidence of inflammation, and was more often associated with a reduction in the numbers of lactobacilli during gel use. The clinical significance of the recruitment of cells susceptible to HIV infection to the genital mucosa remains to be determined.

A placebo-controlled, double-blind prospective study in healthy female volunteers of dextrin sulphate gel: a novel potential intravaginal virucide.

A double-blind, placebo-controlled study was designed to evaluate the safety and tolerability of intravaginal dextrin sulphate (D2S) gel to assess its preliminary suitability as a potential vaginal virucide. Tolerability was assessed by questionnaire and patient interview. Colposcopy with vaginal biopsy was performed to assess the macroscopic and microscopic evidence of inflammation. The potential impact of the gel on normal vaginal flora was examined by quantitative lactobacilli culture with assessment of the ratio of peroxide to nonperoxide-producing organisms. Colposcopy revealed mild erythema in five of 24 subjects receiving active gel and in none of the 12 placebo recipients, but histology in all subjects revealed no evidence of inflammation. No impact on vaginal lactobacilli was found. We conclude that D2S gel is safe and well tolerated intravaginally at the dosing schedule used in this study.

Safety and activity of saquinavir in HIV infection.

We evaluated saquinavir, an orally active, selective inhibitor of HIV proteinase, in a randomised, double-blind, dose-ranging study in 49 zidovudine-naive HIV-positive patients with few or no symptoms and CD4 cell counts of 500 or less. The study was designed to assess the antiviral activity and tolerability of saquinavir. Patients were randomised to receive 25, 75, 200, or 600 mg of saquinavir three times daily for 16 weeks. No serious adverse events occurred. CD4 cell counts showed a trend indicative of a dose response in favour of the 600 mg dosage, the maximum increase being seen around week 4. In none of the 8 patients with positive plasma viraemia at baseline did cultures become negative after treatment; peripheral blood mononuclear cell and plasma-viral load by culture and DNA and RNA PCR all showed a trend towards reduction at higher doses of saquinovir. Saquinavir was well tolerated in this group of previously untreated patients with few or no symptoms; this study shows that an HIV-proteinase inhibitor is active in HIV-infected patients.

Menstrual symptoms in women infected by the human immunodeficiency virus.

OBJECTIVE: To determine whether there is a higher prevalence of menstrual symptoms in women seropositive for the human immunodeficiency virus (HIV) compared to a matched control group and to examine the relation between menstrual symptomatology and immunosuppression. METHODS: In a cross-sectional study, 55 HIV-seropositive women and a matched control group underwent detailed gynecologic assessment. The prevalence of regular cycles, oligomenorrhea, amenorrhea, menorrhagia, dysmenorrhea, and dyspareunia was assessed in the two groups. Any association with clinical disease or CD4 lymphocyte count was sought. RESULTS: There were no significant differences in the prevalence of oligomenorrhea, amenorrhea, menorrhagia, dysmenorrhea, or dyspareunia between the groups. Furthermore, no differences were demonstrated between symptomatic and asymptomatic women infected by HIV, nor was any correlation found between CD4 lymphocyte count and menstrual loss or dysmenorrhea. CONCLUSION: Infection with HIV and related immunosuppression do not seem to have a clinically significant effect on menstruation.

HIV infection and the gynaecologist.

PIP: As women infected with human immunodeficiency virus (HIV) will soon account for 1 in 500 gynecological patients in Great Britain, gynecologists have an obligation to become informed about the transmission, clinical manifestations, and management of HIV. Women with HIV infection are at increased risk of lower genital tract neoplasia with extensive cervical, vaginal, and vulvar lesions. There is also a strong association between HIV infection and sexually transmitted diseases involving genital ulcerations. In fact, herpes, warts, and candidiasis may be the initial clinical presentation of HIV infection. Estradiol levels may fall in seropositive women, but, in general, menstruation and ovulation are maintained. Latex condoms remain the only contraceptive choice for HIV-infected women. Sufficient data have not been accumulated on the effectiveness of the female condom, but it has the potential of giving women in developing countries in particular greater control over HIV prevention. Condom use is essential even if both partners are HIV-positive since the acquisition of different HIV strains can accelerate disease progression. Given their higher risk of percutaneous in injury compared to other surgeons, gynecologists should use double gloving and blunt tipped needles and staples.^ieng

Women with HIV presenting at three London clinics between 1985-1992.

OBJECTIVE: To determine the changing patterns of HIV infection in women in three units in London. SUBJECTS: Three hundred and fifty seven HIV seropositive women who have attended outpatient clinics between 1984 and 1992. METHODS: A retrospective review of data obtained from a computerised database and supplemented by direct inspection of the notes. RESULTS: The number of newly identified women with HIV has risen steadily over the period of study with a significant shift towards a heterosexual mode of transmission. This is a reflection of increasing numbers of women from Sub-Saharan Africa rather than a rise in the incidence of HIV in women born in the UK. CONCLUSIONS: The increase in women infected by HIV remains predominantly restricted to women in "high risk" groups. Although encouraging, our data should be interpreted with caution since it suffers from the inherent bias of selective testing. Safer sex education and epidemiological surveillance should continue despite the apparent low risk to women born in the UK.

Is endometrial infection with Candida albicans a cause of recurrent vaginal thrush?

OBJECTIVE: It was hypothesised that the endometrium might act as a reservoir for candida, thus infecting the vagina as the endometrium is shed during menstruation. DESIGN: A prospective study of women with recurrent vulvo-vaginal candidiasis. The endometrium was sampled and cultured for candida species. SETTING: Central London STD clinic. SUBJECTS: 26 women were enrolled, of whom 20 completed the study. RESULTS: One patient had a positive endometrial culture for candida species, the isolate being Candida krusei. CONCLUSIONS: The endometrium is not a common resevoir for candida species and therefore, infection at this site is an unlikely cause of recurrent vaginal candidiasis.

Is HIV infection associated with an increase in the prevalence of cervical neoplasia?

OBJECTIVE: To test the hypotheses: (1) that HIV infection predisposes to cervical intraepithelial neoplasia (CIN); (2) that this CIN is a result of HIV related immunosuppression; and (3) that this CIN is a result of immunosuppression causing increased expression of the potentially oncogenic viruses, human papilloma virus (HPV), Epstein Barr virus (EBV) and herpes simplex virus (HSV). DESIGN: A matched cross sectional study. SETTING: The Department of Gynaecological Oncology, The Samaritan Hospital, London; the Department of Genitourinary Medicine, St Mary's Hospital, London; and the Family Planning Clinic, Claremont Terrace, Glasgow. SUBJECTS: Fifty HIV seropositive women enrolled from the Genitourinary Medicine Department and the Drug Dependency Unit at St Mary's Hospital, London, and the Unit of Infectious Diseases at Ruchill Hospital, Glasgow. Forty-three HIV seronegative controls enrolled from the Department of Genitourinary Medicine at St Mary's Hospital, matched against 43 of the seropositive women for age, age at first intercourse, lifetime number of sexual partners, and smoking habit. MAIN OUTCOME MEASURES: Associations between CIN, as detected by cytology and histology, and HIV infection. Association was also sought between CIN and immunosuppression, as measured clinically by T4 cell number, beta-2-microglobulin and p24 antigen. Associations of these with: (1) HPV, as detected by Southern blot testing and the polymerase chain reaction; (2) EBV, as detected by Southern blot testing; and (3) HSV, as detected by tissue culture of endocervical swabs, was also studied. RESULTS: There was no significant difference in the prevalence of CIN or oncogenic viruses between HIV seropositive and seronegative women in the absence of immunosuppression. If the HIV infected women showed signs of immunosuppression, the prevalence of CIN was increased. No association was shown between detection of HPV, EBV and HSV and immunosuppression or CIN. CONCLUSION: HIV infection may only be associated with an increased risk of CIN when immunosuppression is present.

Epstein-Barr virus associated oesophageal ulcers in AIDS.

Epstein-Barr virus (EBV) associated ulceration has not previously been included in the differential diagnosis of oesophageal ulcers in AIDS. We report five cases of oesophageal ulceration in homosexual men with advanced human immunodeficiency virus infection in whom this was considered to be the most likely cause. DNA in situ hybridisation studies showed EBV in biopsy material from three of four patients with oesophageal ulcers and in none of three controls. Of other viruses studied, only human papillomavirus was present, and this was found in both patients and control subjects. These findings support the hypothesis that EBV is an aetiological factor in some cases of AIDS-associated oesophageal ulceration.

Comparison of ofloxacin with doxycycline in the treatment of non-gonococcal urethritis and cervical chlamydial infection.

The efficacy of ofloxacin was compared with that of doxycycline in the treatment of non-gonococcal urethritis (NGU) and cervical chlamydial infection in an open randomized study. In total, 182 men and 100 women were enrolled: 92 men and 50 women received ofloxacin at a dose of 400 mg once daily for seven days, and 90 men and 50 women received doxycycline at a dose of 100 mg twice daily for seven days. All women and 42 men, that is 29 men in the ofloxacin group (32%) and 13 in the doxycycline group (14%) were chlamydia-positive on entry into the study. Patients were reviewed on completion of the treatment course (day 8) and two weeks later (day 22). Clinical cure rates for NGU in assessable patients in each treatment group were similar; 73% in the ofloxacin group and 63% in the doxycycline group at day 8, and 70% and 90% in the respective treatment groups on study completion. Repeat tests for chlamydiae were negative for all male and female patients at both day 8 and day 22. Both ofloxacin and doxycycline were well tolerated. We conclude that ofloxacin given at a dose of 400 mg once daily for seven days is a safe and effective alternative treatment for NGU and cervical chlamydial infection.

Gummatous lesions in men infected with human immunodeficiency virus and syphilis.

Two HIV-infected men are reported who developed gummatous lesions more than 12 months after appropriate treatment of presumptive syphilis. In one patient the lesions developed without any change in the VDRL titre. The most likely explanation for these lesions is reactivation of syphilis in the context of HIV infection. As these lesions respond to penicillin, the possible reactivation of appropriately treated syphilis, or even yaws, should now be considered in any ulcerative lesion in HIV infected individuals at risk from treponemal infection.