Nevirapine-associated toxicity in HIV-infected Thai men and women, including pregnant women.

OBJECTIVES: The aim of the study was to determine the incidence of, and risk factors for, nevirapine (NVP)-associated hepatotoxicity and rash in HIV-infected Thai men and women, including pregnant women, receiving NVP-containing highly active antiretroviral therapy (HAART). METHODS: NVP-containing HAART was prescribed to eligible men and women enrolled in the Prevention of Mother-To-Child Transmission of HIV (PMTCT) and MTCT-Plus programmes. All pregnant women received zidovudine (ZDV)/lamivudine (3TC)/NVP from >14 weeks of gestational age if their CD4 cell count was 28 weeks if their CD4 cell count was >200 cells/microL. Patients followed for at least 8 weeks after starting HAART or until delivery were included in the analyses. RESULTS: Of 409 patients, 244 were pregnant women, 87 were nonpregnant women and 78 were men. Hepatotoxicity occurred in 15.6% of all patients. Men had a significantly higher rate of asymptomatic hepatotoxicity (P=0.021). Pregnant women receiving HAART for PMTCT (92% had CD4 cell counts >250 cells/microL) had a significantly higher rate of symptomatic hepatotoxicity (P=0.0003) than pregnant women receiving HAART for therapy. Rash occurred in 16.1% of all patients. The patients' sex and baseline CD4 cell count were not associated with the risk of hepatotoxicity or rash. NVP was discontinued in 4.2% and 6.8% of patients because of hepatotoxicity and rash, respectively. CONCLUSIONS: The incidence of NVP-related hepatotoxicity and rash in Thai adults is similar to incidences reported for other populations. While larger studies are needed, our data support continued use of NVP-containing regimens as first-line treatment in developing countries for HIV-infected patients, including pregnant women. Pregnant women with high CD4 cell counts may experience higher rates of symptomatic hepatotoxicity and thus require careful clinical and laboratory monitoring.

A comparison of cycle control, efficacy, and side effects among healthy Thai women between two low-dose oral contraceptives containing 20 microg ethinylestradio1/75 microg gestodene (Meliane) and 30 microg ethinylestradio1/75 microg gestodene (Gynera).

The purpose of this study was to compare cycle control, efficacy and side effects of an oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene, with a reference preparation containing 30 microg ethinylestradiol combined with 75 microg gestodene. From the study, it was demonstrated that the two regimens had no difference in cycle control, efficacy, and side effects. The occurrence of spotting and breakthrough bleeding was low and was not different between these two preparations. The most common adverse events in both treatment groups were nausea, vomiting, dizziness, and chloasma. There were no statistically significant change in body weight and blood pressure in both groups at the end of study. It is concluded that both preparations are good cycle control, reliable and low side effects oral contraceptives.

Pharmacodynamic effects of depot-medroxyprogesterone acetate (DMPA) administered to lactating women on their male infants.

Normal postpartum women, who had a spontaneous vaginal delivery of one full-term male infant, free of congenital abnormalities and other diseases, were recruited for this study. Thirteen women received 150 mg depot-medroxy-progesterone acetate (DMPA), intramuscularly on days 42 + 1 and 126 + 1 postpartum. Infants of nine mothers, who did not receive DMPA, served as controls. Blood samples were collected from treated mothers on days 44, 47, 74, 124, 128, and 130 postpartum for medroxyprogesterone acetate (MPA) measurements. Four-hour urine collections were obtained from all 22 infants in the morning on days 38, 40, 42, 44, 46, 53, 60, 67, 74, 88, 102, 116, 122, 124, 126, 128, 130, and 137. Urinary follicle stimulating hormone (FSH), luteinizing hormone (LH), unconjugated testosterone, and unconjugated cortisol were measured by radioimmunoassay, and serum MPA and urinary MPA metabolites were measured by gas chromatography-mass spectrometry (GC-MS). No MPA metabolites could be detected in the urine of the infants from the DMPA-receiving mothers. Hormonal profiles in the urine samples were not suppressed in comparison with those of the control infants. The present study demonstrates that DMPA, administered to the mother, does not influence the hormonal regulation of the breast-fed normal male infant.

Trabecular bone in long-term depot-medroxyprogesterone acetate users.

A cross-sectional study was designed to determine trabecular bone density in 75 long-term depot-medroxyprogesterone acetate (DMPA) users (> 3 yr) matched with non-DMPA users by age, body mass index (18-25), limitation of age (< 45 yr), and body weight (< 60 kg). The long-term DMPA cases were divided into 3 groups according to duration of injectable contraceptive use. Neither cases nor controls had a smoking or chronic alcohol consumption history. Cases and controls were matched by age. Trabecular bone of the femoral neck were assessed by X-ray and interpreted by a single-blinded radiologist. Trabecular bone patterns were graded according to Singh's Index. Blood collection for determination of estradiol, prolactin, calcium, phosphorus, and medroxyprogesterone acetate were performed in cases and controls. Venous blood was taken at twelfth week of injection of DMPA and within 5 days after menstrual bleeding cessation in the controls. Mean trabecular bone in the cases was 5.5 +/- 0.6 (range 4-6). It was not statistically different from that in the controls (mean 5.5 +/- 0.6, range 2-6). No statistically significant difference of serum, calcium, phosphorus, prolactin, and estradiol was seen in the cases when compared to controls at mid follicular phase of normal menstrual cycle. Serum MPA of individual case at twelfth week of injection was 4.1 +/- 1.1 nmol/l. In conclusion, trabecular bone density in long-term DMPA users were not statistically different from normal menstruating women who have not received injectable DMPA.

PIP: A cross-sectional study was designed to determine trabecular bone density in 75 long-term depot-medroxyprogesterone acetate (DMPA) users ( 3 years) matched with non-DMPA users by age, body mass index (18-25), limitation of age ( 45 years), and body weight ( 60 kg). The DMPA cases were divided into 3 groups. Group 1 contained women who had used injectable contraceptives for 3-5 years; group 2 comprised women who had used DMPA for 6-7 years; and group 3 consisted of women who had used injectables for more than 7 years. Volunteers received 150 mg (3 ml) of DMPA every 12 weeks. Neither cases nor controls had a smoking or chronic alcohol consumption history. Cases and controls were matched by age. Trabecular bones of the femoral neck were assessed by X-ray and interpreted by a single-blinded radiologist. Trabecular bone patterns were graded according to Singh's Index. Determination of estradiol, prolactin, calcium, phosphorus, and DMPA in blood was performed in cases and controls. Venous blood was taken at the 12th week of injection of DMPA and within 5 days after menstrual bleeding cessation in controls. The mean serum level for calcium ranged from 9.3 to 10.1 mg% and 3.2 to 3.5 mg% for phosphorus. The mean serum level for estradiol in the 3 DMPA user groups ranged from 122.9 pmol/l to 167.7 pmol/l compared to 141.9 pmol/l to 195 pmol/l in controls. Mean trabecular bone in Group 3 of cases (n = 25) was 5.5 +or- 0.6. It was not statistically different from that in the controls (n = 49) (mean 5.5 +or- 0.6). There were no statistically significant differences in serum calcium, phosphorus, prolactin, and estradiol levels in cases compared to controls at the mid-follicular phase of normal menstrual cycle. Individual serum MPA at the 12th week of injection was 4.1 +or- 1.1 nmol/l. Trabecular bone density in long-term DMPA users was not statistically different from normal menstruating women who had not received injectable DMPA.