Surasith Chaithongwongwatthana

Efavirenz, in contrast to nevirapine, is associated with unfavorable progesterone and antiretroviral levels when coadministered with combined oral contraceptives.

Background:Effective contraception has been widely promoted for HIV-positive women. However, there are limited data on the interactions between combined hormonal contraceptives and nonnucleoside reverse transcriptase inhibitors . Methods:This study assessed the steady-state contraceptive effectiveness and safety of combined oral contraceptive (COC) containing 0.150 mg desogestrel /0.030 mg ethinyl estradiol with either nevirapine (NVP) or efavirenz (EFV) in 34 HIV-positive women. The targeted level for contraceptive effectiveness was endogenous progesterone level < 3.0 ng/mL. We measured NVP/EFV plasma concentrations 12 hours after administration (C12) with and without COC. The desired therapeutic levels were >3.1 mg/L for NVP and 1.0–4.0 mg/L for EFV, respectively. Results:All 18 subjects in the NVP group had serum progesterone <1.0 ng/mL. Four of 16 subjects (25%) in the EFV group had serum progesterone >1.0 ng/mL, including 3 subjects with >3.0 ng/mL (might indicate ovulation). The difference in progesterone levels between the 2 groups was statistically significant (P = 0.04). The median C12 of NVP increased insignificantly by 17% with COC; the median C12 of EFV decreased significantly (P = 0.02) by 22%. In 3 of 16 subjects (19%) in the EFV group, C12 of EFV dropped below 1.0 mg/L. Conclusions:In contrast to NVP, coadministrating desogestrel/ethinyl estradiol containing COC with EFV was associated with unfavorable progesterone and antiretroviral levels. Our results suggest that NVP may be superior to EFV when used with COC in HIV-positive women.

Does Indomethacin Prevent Preterm Birth in Women with Cervical Dilatation in the Second Trimester

We sought to estimate the effect of indomethacin on duration of pregnancy in women with dilated cervix between 14 (0)/ (7) to 25 (6)/ (7) weeks. Demographics, risk factors, and outcomes were compared in women 14 (0)/ (7) to 25 (6)/ (7) weeks with a dilated cervix > or = 1 cm who received indomethacin versus no indomethacin therapy, stratified for cerclage. Primary outcome was interval from presentation until delivery. Of 222 singleton gestations, 68 (31%) received indomethacin. In unadjusted and adjusted analyses, no significant differences were observed in interval from presentation to delivery and preterm birth < 28, < 32, or < 35 weeks comparing the indomethacin and no indomethacin groups, even after stratification for cerclage. In multivariate logistic regression analysis limited to women receiving cerclage, preterm birth < 32 weeks (odds ratio 0.56, 95% confidence interval 0.26, 1.25) and < 35 weeks (odds ratio 0.52, 95% confidence interval 0.23, 1.14) suggested a possible but not significant benefit for indomethacin use. Indomethacin therapy in women with dilated cervix at 14 (0)/ (7) to 25 (6)/ (7) weeks, regardless of cerclage or not, had no effect on pregnancy outcomes.

Nadir CD4 count and monthly income predict cervical squamous cell abnormalities in HIV-positive women in a resource-limited setting.

We conducted a cross-sectional study with 385 HIV-positive women in Bangkok to assess the prevalence and predictors of cervical abnormalities on Papanicolaou (Pap) smear. Low-grade squamous intraepithelial lesions (LSIL), high-grade SIL (HSIL) and invasive cervical cell cancer (ICC) were assessed by cytological examination after Pap smear and logistic regression models were used to assess associations with patient characteristics. Overall prevalence of LSIL, HSIL and ICC were 11.2% (95% confidence interval [CI] 8.2-14.7%), 4.7% (95%CI 2.8-7.3%) and 0.5% (95%CI 0.06-1.9%), respectively. In multivariate models, only the nadir CD4 count and income remained significantly associated with cytological abnormalities, whereas smoking, hormonal contraceptive or antiretroviral use, condom use, parity and number of lifetime sexual partners were not associated. The odds ratio for having cytological abnormalities was 2.6 (95% CI 1.24-5.34) in those with a nadir CD4 count <200 cells/mm3 compared with those with a higher nadir CD4 count, and 1.99 (1.11 -3.57) in those with an income of <125 US dollars/month compared with those with higher incomes. In settings where access to affordable treatment is improving, this study reinforces the importance of regular Pap smear screening in HIV-positive women, particularly those with low nadir CD4 counts and lower incomes.

Chromosomal abnormalities among 246 fetuses with pleural effusions detected on prenatal ultrasound examination: Factors associated with an increased risk of aneuploidy

Purpose: To determine the prevalence of chromosomal abnormalities in fetuses with prenatally diagnosed pleural effusions and to identify factors associated with an increased risk of aneuploidy.Methods: A retrospective analysis of the Genzyme Genetics database was performed for samples submitted from October 1994 to April 2003 with an indication of fetal pleural effusion.Results: There were 246 samples in which pleural effusion was identified as an indication for prenatal chromosome analysis. Ninety-four were from fetuses with isolated pleural effusions and 152 had other abnormalities in addition to pleural effusion. The prevalence of chromosome abnormalities was 35.4% (95% confidence interval, 29.2–41.4%). Among the eight first trimester samples, the aneuploidy rate was 63%. Pleural effusion cases associated with additional sonographic findings had a significantly higher aneuploidy rate than the isolated pleural effusion cases (50% vs. 12%, P < 0.001).Conclusions: Chromosome analysis is warranted after the prenatal detection of a fetal pleural effusion. The risk of aneuploidy is greater with first trimester detection and is significantly increased in the presence of other associated anomalies.

Age at menopause and menopause-related symptoms in human immunodeficiency virus-infected Thai women.

Objective There are limited data for age at menopause (AM) and menopause-related symptoms in human immunodeficiency virus (HIV)–infected Asian women. We investigated AM and menopause-related symptoms in HIV-infected Thai women. Methods HIV-infected Thai women 40 years or older who did not receive any hormone therapy in the 8-week period preceding the study were enrolled. Participants completed the Menopause-Specific Quality of Life survey for their symptoms in the past 30 days. Menopause was defined as having the last menstrual period more than 1 year ago. Multivariate Cox proportional hazard regression analysis was used to identify factors associated with menopause. Results Two hundred sixty-eight HIV-infected women were enrolled; their median age was 44.6 (41.8-48.7) years, and the ratio of their Centers for Disease Control and Prevention clinical classifications (A:B:C) was 53%:34%:13%; 95% were using highly active antiretroviral therapy. The median (interquartile range [IQR]) CD4 count was 575 (437-758) cells/&mgr;L, and 93% had HIV-RNA of less than 1.7log10 copies/mL. Among the 55 women who had reached menopause, the mean (SD) AM was 47.3 (5.1) years. The mean (SD) AM in our study was earlier than the previous report of 49.5 (3.6) years in non–HIV-infected Thai women (difference, −2.2 y; 95% CI, −3.2 to −1.2, P < 0.01). Postmenopausal women had more symptoms, including night sweats (P = 0.03), change in sexual desire (P = 0.01), and avoiding intimacy (P = 0.01), compared with nonpostmenopausal women. No differences in psychosocial or physical domains between groups were found. Factors associated with menopause were Centers for Disease Control and Prevention clinical classification B or C (hazard ratio, 1.7; 95% CI, 1.0-3.03, P = 0.04), and no sexual act in the past month (hazard ratio, 4.9; 95% CI, 1.5-16.0, P = 0.01). No associations of later age of menarche, parity, marital status, educational level, income, body mass index, CD4 count, and HIV-RNA with menopause were found. Conclusions AM in HIV-infected Thai women was 47.3 years, which is significantly earlier than the findings of a previous AM report on non–HIV-infected women. Postmenopausal HIV-infected women had more vasomotor and sexual symptoms. More studies are needed to investigate the cause and appropriate interventions for accelerated menopause in HIV-infected women.

Thai HIV-1-infected women do not require a dose increase of lopinavir/ritonavir during the third trimester of pregnancy.

Objectives:To investigate whether Thai HIV-1-infected pregnant women require a dose increase of lopinavir/ritonavir (LPV/r) and to assess the safety and efficacy of the generic tablets during pregnancy. Design:Prospective, single-center pharmacokinetic study. Methods:HIV-infected pregnant, antiretroviral therapy-naive or experienced women started HAART containing generic LPV/r 400/100 mg tablets twice daily. The 12-h pharmacokinetic curves were recorded at gestational age 20 weeks (GA20, optional), 33 weeks (GA33) and 12 weeks postpartum (12PP, optional). Results:Twenty women were included. Median [interquartile range (IQR)] age was 28 (25–33) years and mean (SD) weight at GA33 was 59.9 (4.2) kg. Mean (SD) values for LPV area under the curve0–12 h, Cmax, Cmin, and Thalf were 72.9 (19.2) mg/l h, 9.3 (2.2) mg/l, 3.2 (1.3) mg/l and 4.8 (2.4) h, respectively, on GA33 and 98.0 (24.1) mg/l h, 11.7 (2.2) mg/l, 4.7 (2.2) mg/l and 5.9 (2.7) h, respectively on 12PP. Twelve women recorded both GA33 and 12PP curves; mean LPV AUC0–12 was significantly lower at GA33 [−24.1 (95% confidence interval −44.4 to –3.7) mg/l h]. At GA33, 19 of 20 women had sufficient LPV trough concentrations (>1.0 mg/l) and at 12PP, all had sufficient LPV trough concentrations. None of the women stopped LPV/r before planned discontinuation due to side-effects. At delivery, 19 of 20 women had a viral load below 50 copies/ml. One woman had a viral load of 60 copies/ml, but was undetectable at 12PP. Conclusion:Standard dose generic LPV/r (400/100 mg twice daily) in Thai HIV-1-infected pregnant women leads to adequate plasma concentrations during the third trimester. The generic LPV/r tablet is well tolerated and effective for use during pregnancy.

Anal squamous intraepithelial lesions among HIV positive and HIV negative men who have sex with men in Thailand.

Objectives: To evaluate the prevalence and risk factors of anal squamous intraepithelial lesions (ASIL), the putative anal cancer precursor, in Asian HIV positive and HIV negative men who have sex with men (MSM). Methods: Men who underwent anal Pap smear reported clinical, sociodemographic and behavioural information collected through questionnaire and interview between January 2007 and April 2008. χ2 and logistic regression were used to evaluate ASIL prevalence and risk factors among HIV positive and HIV negative MSM. Results: Of the 174 MSM (mean age 32.1 years), 118 (67.8%) were HIV positive. Overall, 27% had abnormal anal cytology: 13.2% had atypical squamous cells of undetermined significance (ASC-US), 11.5% had low-grade squamous intraepithelial lesion (LSIL) and 2.3% had high-grade squamous intraepithelial lesion (HSIL). Prevalence of ASIL was higher among HIV positive than HIV negative MSM (33.9% vs 12.5%; p = 0.003). Among HIV positive MSM, 16.1% had ASC-US, 14.4% had LSIL and 3.4% had HSIL and 7.1%, 5.4% and 0% in HIV negative MSM, respectively. Anal condyloma was detected in 22% of HIV positive and 16.1% (9/56) of HIV negative MSM (p = 0.5). In HIV positive MSM, anal condyloma (OR 3.42, 95% CI 1.29 to 9.04; p = 0.01) was a significant risk factor for ASIL. Highly active antiretroviral therapy use and CD4+ T cell count were not associated with ASIL. Conclusions: One-third of HIV positive and 12.5% of HIV negative MSM had ASIL. Thus, as greater numbers of HIV positive MSM live longer due to increasing access to HAART worldwide, effective strategies to screen and manage anal precancerous lesions are needed.

Sexual life, options for contraception and intention for conception in HIV-positive people on successful antiretroviral therapy in Thailand

Abstract This article reports on the sexual life of HIV-positive heterosexual men and women in a stable relationship and on successful antiretroviral therapy in Thailand. We focused on one side on their sexual practices and options for contraception, and on the other on their intention for conception and factors influencing it, in the time of highly active antiretroviral therapy. In a cross-sectional study, 200 participants completed a questionnaire. Eleven female participants took part in focus group discussions (FGD), based on their intention for conception. We used descriptive statistics, logistic regression, and Chi-square exact test to present the results from the questionnaire, and a narrative approach for the FGD results. The median age of the participants was 37 years. Almost all were sexually active (88%) and rarely engaged in risky sexual behavior. The most common method of contraception for women was the male condom (95%), followed by female sterilization (40%). Almost all men reported consistent condom use. One-third of the main sexual partners were HIV-negative. The intention for conception was significantly less after being diagnosed with HIV (29% intended pregnancies after HIV diagnosis vs. 72% before HIV diagnosis). Nevertheless, 25% of the participants expressed a desire to have a child. We found a significant positive association between the intention for conception and less years of being married, the lower number of children and the higher levels of education. Therefore, we conclude that HIV-positive men and women are sexually active and in need of comprehensive reproductive health care services including counseling on safe ways to conceive and offering a diverse choice of contraceptive methods to those who do not wish to have children.

Significant decrease of ethinylestradiol with nevirapine and of etonogestrel with efavirenz in HIV-positive women.

INTRODUCTION According to the World Health Organization, there are “no restrictions on the use of any hormonal contraceptive method for women living with HIV or at high risk of HIV.” Nevertheless, there are many unanswered questions in this field. Sex steroid hormones and certain antiretrovirals (ARVs), such as nonnucleoside reverse transcriptase inhibitors, have common metabolic pathways, mainly through the cytochrome P450 enzyme system, especially Cyp3A4. As a result, pharmacokinetic (PK) interactions lead to changes in their blood levels and possible changes in their therapeutic activity. Comparison between the few existing studies is limited by the differences in study population and contraceptive products used. In an earlier study, we assessed the contraceptive effectiveness and safety of combined oral contraceptive (COC) pills in HIV-positive women taking nevirapine (NVP)-based or efavirenz (EFV)based therapy. We found that the co-administration of desogestrel (DSG)/ ethinyl estradiol (EE2) contraceptive pills in the NVP group did not affect the effectiveness of the contraceptive pills, based on the measurement of endogenous progesterone. In contrast, in the EFV group, the co-administration of DSG/EE2 contraceptive pills led to a possible compromise in both the contraceptive effectiveness of DSG/EE2 and the ARV activity of EFV. In this article, we report etonogestrel (ENG), the active metabolite of DSG, and EE2 levels from this cohort, thus substantiating our initial findings and contributing to the scarce literature on this subject.

Uptake and continuous use of copper intrauterine device in a cohort of HIV-positive women

Copper intrauterine device (IUD) is not commonly used in many countries, though it provides effective reversible contraception with no or minimal primary systemic side effects. We assessed its uptake and continuation of use among HIV-positive Thai women. Sixty-six of 322 women of reproductive age, whom we approached for the study, met the eligibility criteria. Sterilization (62%) was the main reason for failure to enroll. Twenty-nine of them (44%) underwent IUD insertion. Considering condom use sufficient for pregnancy prevention (12%) was the main reason among eligible women for the refusal to participate in the study. At six months, 54% of enrolled participants reported one or more side effects such as increased menstrual flow (43%), spotting (21%) and dysmenorrhea (11%). The continuation rate of IUD use was high (93%), in spite of the persistent non-systemic side effects. The study showed that copper IUD could be an acceptable contraceptive choice for Thai HIV-positive women. Easy access to the method in a setting linked with the HIV service, and education on IUD risks and benefits is needed to promote the use of IUD in addition to condoms as an effective contraceptive option in HIV-infected women.