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1.
BACKGROUND: In the United States, as most highly active antiretroviral therapy (HAART) regimens used during pregnancy in HIV-infected women include a protease inhibitor (PI), it is important to determine the effects of PIs specifically rather than all HAART regimens. Prospective trials employing HAART during pregnancy are ongoing. OBJECTIVE: To better understand the effects of PI use during pregnancy on prematurity, maternal and infant adverse events, and infant outcomes. RESULTS: A total of 233 pregnancies in which PIs were used were reported, including 5 sets of twins and 1 set of triplets. Perinatal transmission is documented in 2 of 221 infants for a rate of 0.9% (95% CI, 0%-2.2%). Both HIV-positive infants were delivered by cesarean section (one elective at 37 1/7 weeks and one unscheduled at 32 6/7 weeks). The prematurity rate (<37 weeks' gestation) was 22.0% (95% CI, 16.9%-28.0%) including 3 twin and 1 triplet pregnancies. In multiple regression analysis no association was noted for individual PIs or the week of gestation that PIs were initiated. Adverse maternal, obstetric, and infant events possibly related to PIs were uncommon. CONCLUSIONS: In this series, PIs during pregnancy appeared generally safe for mothers and infants. Perinatal transmission was low and the prematurity rate is similar to prior data in HIV-positive women not on PIs.  相似文献   

2.
Concerns have been raised over possible adverse effects of prophylactic antiretroviral therapy (ART) on the fetus and newborn. We analyzed data relating to uninfected children enrolled in the European Collaborative Study and investigated the association between ART exposure, perinatal problems, and major adverse health events later in life. Median length of follow-up was 2.2 (0-15.9) years. Of the 2414 uninfected children, 687 (28%) were exposed to ART in all three periods (antenatal, intrapartum, and neonatal). Of the 1008 infants exposed to ART at any time, 906 (90%) were exposed antenatally, 840 (83%) neonatally, and 750 (74%) both antenatally and neonatally. ART exposure was not significantly associated with pattern or prevalence of congenital abnormalities or low birth weight. In multivariate analysis, prematurity was associated with exposure to combination therapy without a protease inhibitor (PI) (OR = 2.66; 95% CI: 1.52-4.67) and with a PI (OR = 4.14; 95% CI: 2.36-7.23). ART exposure was associated with anemia in early life ( <.001). There was no evidence of an association with clinical manifestations suggestive of mitochondrial abnormalities. The absence of serious adverse events in this large cohort of uninfected children exposed to prophylactic ART in the short to medium term is reassuring.  相似文献   

3.
Surveys in HIV-infected men on antiretroviral therapy (ART) consistently demonstrate decreased levels of peripheral fat, with variable effects on central fat. This substudy of the Women's Interagency HIV Study was undertaken to examine fat distribution in a well-characterized cohort of HIV-positive and HIV-negative women in the United States. Whole-body dual-energy x-ray absorptiometry scanning with standardized regional analysis was performed in 271 nonpregnant women. Results were compared in the following groups: HIV negative (n = 88); and HIV positive on no ART (n = 70), highly active ART with a protease inhibitor (HAART/PI) (n = 48), or non-PI-containing HAART (n = 53). The groups were well matched with respect to race, with the majority of women coming from racial/ethnic minorities. The majority of both HIV-positive and HIV-negative women were overweight (body mass index [BMI] >/=25 kg/m), and many were obese (BMI >30 kg/m). Leg fat in both groups on HAART was significantly lower than in HIV-negative women (P = 0.01 and <0.0001 vs. HIV-negative for HAART/PI and HAART/no PI, respectively), whereas trunk fat was lower only in HAART/no PI (P = 0.0004 vs. HIV-negative). Thus, consistent with reports in men, lower levels of peripheral (leg) fat are seen in HIV-infected women on HAART, despite the high prevalence of obesity in this population.  相似文献   

4.
There is an established association between human immunodeficiency virus (HIV) infection and mixed cryoglobulinemia, as demonstrated in studies mostly conducted before the introduction of highly active antiretroviral therapy (HAART). To assess the impact of the latter on the cryoglobulinemic status in patients with HIV infection, 133 consecutive, unselected HIV-positive patients, from which only 8 (6%) had co-infection with hepatitis C virus (HCV), were evaluated for the presence of cryoglobulins, according to whether they received or not antiretroviral therapy (ART). Patients shown to be cryoglobulin-positive in a previous study were assessed prospectively, after introducing HAART. Cryoglobulinemia was found in 10 (7.5%) of 133 patients:4 (3.9%) of 101 patients receiving ART versus 6 (18.8%) of 32 patients not receiving ART (P = 0.013). When HCV-positive patients were excluded from the analysis, the correlation between cryoglobulinemia and ART remained significant (P = 0.019). Among 11 previously detected cryoglobulin-positive patients, 8 became cryoglobulin-negative after receiving HAART for a mean period of 6.5 years (P = 0.039). Thus, ART seems to decrease the prevalence of cryoglobulinemia in HIV-infected, HCV-negative patients, a finding which provides indirect evidence of the etiologic role of HIV in the pathogenesis of cryoglobulins.  相似文献   

5.
BACKGROUND: Millions of HIV-infected women in developing countries are in need of safe and highly effective antiretroviral therapy. Pregnancy rates are usually high in developing countries, and efavirenz (EFV) use in women of childbearing age is of concern because of its potential teratogenicity. METHODS: As part of a prospective study comparing 6 initial highly active antiretroviral therapy (HAART) regimens, 3 of which contained EFV, pregnancy and birth outcomes were evaluated among female participants enrolled in a randomized clinical trial in Botswana. Before enrollment, all female participants indicated a willingness to avoid pregnancy for the 3-year duration of the study. Monthly urine pregnancy testing and regular contraceptive education and counseling were given to all women on study. RESULTS: Four hundred fifty-one (69.4%) of 650 enrolled study participants were female and experienced 71 pregnancies, for a rate of 7.9 per 100 person-years during the study. The mean time from HAART initiation to time of first pregnancy was 385 days. The median birth weight of babies was 2950 g (interquartile range: 2700-3250 g); the gender of babies (24 female and 15 male) and occurrence of early pregnancy loss (42%) and stillbirths (3%) did not differ between EFV- and non-EFV-exposed pregnancies (P=0.7). First-trimester EFV exposure occurred in 38 (53.5%) of the 71 pregnancies; 22 (57.9%) of these 38 pregnancies resulted in live births. One infant (4.5%) of the 22 EFV-exposed live births had a congenital abnormality with right limb shortening that was assessed to be unrelated to EFV exposure. CONCLUSIONS: The restoration of health and longevity in many HAART-treated women is often accompanied by childbearing, as evidenced by the large fraction of women in our cohort who became pregnant despite their initial statements of intent to avoid pregnancy. Of 22 first-trimester EFV-exposed live births, 1 neonate was found to have a major congenital abnormality; however, this defect was unrelated to EFV exposure. The small sample size is insufficient to estimate accurately the underlying risk of congenital malformation after exposure to EFV in early pregnancy, underscoring the importance of reporting to the existing international Antiretroviral Pregnancy Registry. In addition to accessing safe and effective HAART regimens, HIV-infected women require access to comprehensive family planning services, including contraception and procreation counseling.  相似文献   

6.
OBJECTIVES: To document postpartum disease-free survival of HIV-infected women taking antiretroviral therapy (ART) during pregnancy. METHODS: Laboratory and clinical data were collected on all HIV-infected pregnant women delivering from 1998 to 2002 and followed up until September 2004 at 6 hospitals in London. Mothers were grouped according to receipt of zidovudine monotherapy (ZDVm), highly active antiretroviral therapy (HAART) given during and continued after pregnancy (cHAART), and short-term HAART given during pregnancy and discontinued on delivery (START). RESULTS: Eight-five women took ZDVm, 155 took cHAART, and 71 took START. The mean follow-up for all mothers was 33 months, with a total of 847 person-years. At the first antenatal clinic (ANC) visit, 72% of women were in Centers for Disease Control and Prevention (CDC) stage A, 85% were treatment naive, and the ZDVm group had a median HIV viral load (VL) 10-fold less than those mothers who started HAART during pregnancy. At last follow-up, 1 patient had died and 6 (1.9%) had progressed to CDC stage C; 62% of all women, including a quarter of the ZDVm group, were receiving HAART for their own health; and 83% of all mothers had a VL <50 HIV RNA copies/mL of plasma regardless of whether they were on treatment or not. CONCLUSIONS: The median-term postpartum prognosis of HIV-infected pregnant women with access to HAART is good. Exposure to short-course ZDVm or START during pregnancy did not jeopardize their response to subsequent therapy.  相似文献   

7.
Topical tretinoin (Retin-A) is used to treat acne and photodamaged skin. Its teratogenic potential is of concern due to its similarity to isotretinoin (Accutane), a recognized human teratogen. Through the California Teratogen Information Service and Clinical Research Program, between 1983 and 2003, 106 pregnant women with first-trimester exposure to topical tretinoin were prospectively ascertained and followed. Birth outcomes, including pregnancy loss, major structural defects, and pre- and postnatal growth were compared to 389 similarly and prospectively ascertained women with no topical tretinoin exposure during pregnancy. Because a distinct pattern of malformation had already been described for isotretinoin, we also compared exposed (n = 62) and unexposed (n = 191) infants on the prevalence of a specific subset of minor malformations selected to represent the spectrum of defects comprising the retinoic acid embyopathy. There were no significant differences between groups in the proportion of pregnancies ending in spontaneous abortion (6.6% in exposed vs. 8.5% in unexposed; P = 0.53), or infants with major structural defects (2.2% in exposed vs. 1.2% in unexposed; P = 0.62). In addition, the groups were similar in birth weight, length and head circumference, and there were no significant differences between groups in length of gestation. Furthermore, the prevalence of one or more retinoic acid-specific minor malformations did not differ significantly between groups (12.9% in exposed vs. 9.9% in unexposed; P = 0.51). First-trimester topical tretinoin exposure in this study was not associated with an increased risk of any adverse pregnancy outcome evaluated. Specifically, there was no indication that topical tretinoin is associated with an increased risk for minor malformations that are consistent with the retinoic acid embryopathy. Although it is impossible to exclude the possibility that some women/infants may be uniquely susceptible to topical tretinoin exposure, this study provides further reassurance for women who are inadvertently exposed early in pregnancy.  相似文献   

8.
Highly active antiretroviral therapy (HAART) has been shown to be highly effective in reducing plasma levels of HIV RNA; therefore, these treatments could diminish the risk of transmission. We analyzed 393 steady heterosexual couples, of which one partner had been previously diagnosed with HIV infection (index case) and where the nonindex partner reported his or her sexual relationship with the index case as the unique risk exposure. These couples were consecutively enrolled in the period 1991 through 2003 when the nonindex partners took their first HIV test. HIV prevalence among partners of index cases who had not received antiretroviral therapy was 8.6%, whereas no partner was infected in couples in which the index case had been treated with HAART (P = 0.0123). HIV prevalence among nonindex partners declined from 10.3% during the pre-HAART period (1991-1995) to 1.9% during the late HAART period (1999-2003; P = 0.0061). In the multivariate analysis, this decline held (odds ratio = 0.14, 95% confidence interval: 0.03-0.66) after adjusting for length of partnership, unprotected coitus, and pregnancies as well as gender, CD4 lymphocyte count, AIDS-defining diseases, and sexually transmitted infections in the index case. When HAART became widely available, a reduction of approximately 80% in heterosexual transmission of HIV was observed, irrespective of changes in other factors that affect transmission.  相似文献   

9.
BACKGROUND: The possible interference of assisted reproduction techniques (ART) with epigenetic reprogramming during early embryo development has recently sparked renewed interest about the reported lower birth weight among infants born as a consequence of infertility treatments. However, the latter finding so far has relied on the comparison of the birth weight of infants conceived with ART to general population data. A more appropriate comparison group should involve pregnancies in infertile women after natural conception. Therefore, we compared neonatal birth weight data of infants born after various ART treatments, including intrauterine insemination (IUI), with those of previously infertile women achieving pregnancy after sexual intercourse. METHODS: Between August 1996 and March 2004 the data of all infertile women presenting in the infertility unit of the University Women's Hospital of Basel, Switzerland, were collected prospectively, adding up to 995 intact pregnancies and deliveries. The birth weight of all infants resulting from 741 singleton pregnancies were analysed with regard to the patients' characteristics, the occurrence of complications during pregnancy and the type of infertility treatment with which the pregnancies were achieved. RESULTS: Comparison of duration of pregnancy and birth weight of infants born after infertility treatment confirms a shorter pregnancy span and a lower mean birth weight in infants born after IVF and ICSI. If women with pregnancies after ART deliver before term, neonatal birth weight is significantly lower. CONCLUSIONS: There is a specific effect of ART, mainly IVF and ICSI, on both shortening the duration of pregnancy and lowering neonatal birth weight. Both these parameters seem to be interrelated consequences of some modification in the gestational process induced by the infertility treatment. Freezing and thawing of oocytes in the pronucleate stage had a lesser impact on pregnancy span and on neonatal birth weight.  相似文献   

10.
OBJECTIVES: To evaluate factors associated with use of HIV specialist care by women, and to determine whether medical indications for therapy validate lower rates of antiretroviral use in women not using HIV specialty care. DESIGN: Cross-sectional analysis of the 1998 interview from the HIV Epidemiology Research Study (HERS) cohort. METHODS: Data from 273 HIV-infected women in the HERS were analyzed by multiple logistic regression to calculate predictors of the use of HIV specialist care providers. Variables included study site, age, education, insurance status, income, substance abuse, depression, AIDS diagnosis, CD4 + lymphocyte count, and HIV-1 viral load. In addition, medical indications for therapy and medical advice to begin antiretroviral therapy were assessed. RESULTS: Of 273 women, 222 (81%) used HIV specialists and 51 (19%) did not. Having health insurance, not being an injection drug user, and being depressed were predictive of using HIV specialist care (all p < or = .05). Although medical indications for therapy in the two groups were comparable, the rate of highly active antiretroviral therapy (HAART) use was significantly higher in women using HIV specialist care (27%) compared with those not using HIV specialists (7.8%). Women using HIV specialists received significantly more advice to begin antiretroviral therapy (ART) in the 6 months prior to the interview compared with those not using specialists (relative risk, 2.4; 95% CI = 1.3-4.6). CONCLUSIONS: Having insurance, not being an injection drug user, and being depressed all increased the likelihood of women receiving HIV specialty care, which, in turn, increased the likelihood of receiving recommended therapies. The level of HAART use (23%) and any ART use (47%) in these HIV-infected women was disturbingly low. Despite comparable medical indications, fewer women obtaining care from other than HIV specialists received HAART. These data indicate substantial gaps in access to HIV specialist care and thereby to currently recommended antiretroviral treatment.  相似文献   

11.
12.
Increasing numbers of HIV-serodiscordant heterosexual couples are concerned about the chances for pregnancy. We reviewed all natural pregnancies attained by HIV-serodiscordant couples seen in 3 clinics in Spain, in which the infected partner had undetectable plasma viremia while receiving highly active antiretroviral therapy (HAART). In the case of HIV-infected mothers, only those with undetectable viremia during pregnancy and at delivery were chosen. A total of 62 HIV-serodiscordant couples, 22 HIV-infected women (mean CD4 count of 522 cells/microL, 55% hepatitis C virus [HCV]-seropositive) and 40 HIV-infected men (mean CD4 count of 629 cells/microL, 75% HCV-seropositive), were recorded. Overall, 76 natural pregnancies occurred, and 68 children were born. There were 9 fetal deaths, 1 twin pregnancy, 6 couples with 2 consecutive babies, and 4 couples with 3 consecutive newborns. There were no cases of HIV seroconversion in uninfected sexual partners. One case of vertical HIV transmission occurred, however. Serodiscordant couples attaining natural pregnancy are exposed to a negligible risk of sexual transmission of HIV when the infected partner presents with complete suppression of plasma viremia while receiving HAART.  相似文献   

13.
A decision analysis model, from a health care system perspective, was used to assess the cost-effectiveness of HIV rescreening during late pregnancy to prevent perinatal HIV transmission in South Africa, a country with high HIV prevalence and incidence among pregnant women. Because new HIV prenatal prophylactic and pediatric antiretroviral therapy (ART) regimens are becoming more widely available, the study was carried out with different combinations of the two. With an estimated HIV incidence during pregnancy of 2.3 per 100 person-years, HIV rescreening would prevent additional infant infections and result in net savings when zidovudine plus single-dose nevirapine or single-dose nevirapine is used for perinatal HIV prevention, and ART was available to treat perinatally HIV-infected children. The cost savings were robust over a wide range of parameter values when ART was available to treat perinatally HIV-infected children but were more sensitive to variations around the baseline when ART was not available. The minimum time interval between the initial and repeat screens would be from 3 to 18 weeks, depending on prophylactic and treatment regimens, for HIV rescreening to be cost saving. Overall, HIV rescreening late in pregnancy in high-prevalence, resource-limited settings such as South Africa would be a cost-effective strategy for reducing mother-to-child transmission.  相似文献   

14.
BACKGROUND: Single-dose nevirapine (SDNVP) is widely used to prevent mother-to-child HIV transmission in resource-limited settings. Given detection of resistant mutants among women who receive SDNVP, concerns have arisen over the efficacy of SDNVP in repeat pregnancies. METHODS: Retrospective data were collected from SDNVP-exposed and -unexposed women from the HIV Network for Prevention 012 trial who subsequently received SDNVP in another pregnancy. Prospective data were collected from pregnant women who were SDNVP exposed or unexposed before delivery. Kaplan-Meier and Cox regression analyses were used to estimate rates of HIV infection and HIV-free survival among infants born to women with or without prior SDNVP exposure. RESULTS: In the retrospective cohort, the infection rates were 11.3% and 16.7% for 104 infants of NVP-exposed and -unexposed mothers, respectively (P = 0.41). In the prospective cohort, among 103 infants of NVP-exposed and -unexposed mothers, the 12-month infant HIV infection rates were 20.5% and 18.7% (P = 0.81) and HIV-free survival rates were 74.4% and 78.1% (P = 0.66), respectively. CONCLUSIONS: There was no increased risk of infant HIV infection among SDNVP-exposed women compared with -unexposed women. These findings support current international guidelines to offer SDNVP to HIV-infected pregnant women, regardless of previous SDNVP exposure, when more complex prophylaxis regimens are not available.  相似文献   

15.
16.
Zidovudine-based antiretroviral therapies (ARTs) for treatment of HIV-infected pregnant women have markedly reduced mother-to-child transmission of the human immunodeficiency virus (HIV-1) from approximately 25% to <1%. However, zidovudine (ZDV; AZT), a nucleoside analogue, induces chromosomal damage, gene mutations, and cancer in animals following direct or transplacental exposure. To determine if chromosomal damage is induced by ZDV in infants exposed transplacentally, we evaluated micronucleated reticulocyte frequencies (%MN-RET) in 16 HIV-infected ART-treated mother-infant pairs. Thirteen women received prenatal ART containing ZDV; three received ART without ZDV. All infants received ZDV for 6 weeks postpartum. Venous blood was obtained from women at delivery and from infants at 1-3 days, 4-6 weeks, and 4-6 months of life; cord blood was collected immediately after delivery. Ten cord blood samples (controls) were obtained from infants of HIV-uninfected women who did not receive ART. %MN-RET was measured using a single laser 3-color flow cytometric system. Tenfold increases in %MN-RET were seen in women and infants who received ZDV-containing ART prenatally; no increases were detected in three women and infants who received prenatal ART without ZDV. Specifically, mean %MN-RET in cord blood of ZDV-exposed infants was 1.67 +/- 0.34 compared with 0.16 +/- 0.06 in non-ZDV ART-exposed infants (P = 0.006) and 0.12 +/- 0.02 in control cord bloods (P < 0.0001). %MN-RET in ZDV-exposed newborns decreased over the first 6 months of life to levels comparable to cord blood controls. These results demonstrate that transplacentalZDV exposure is genotoxic in humans. Long-term monitoring of HIV-uninfected ZDV-exposed infants is recommended to ensure their continued health.  相似文献   

17.
OBJECTIVE: To describe the safety and efficacy of highly active antiretroviral therapy (HAART) in pregnant women treated in an integrated antiretroviral antenatal clinic (ANC ARV). METHODS: A retrospective analysis was performed on patients attending the ANC ARV from August 2004 through February 2007. RESULTS: Data were collected on 689 treatment-naive pregnant women initiated on HAART. The mean age was 29.2 years. The mean baseline CD4 count was 154 cells per microliter, and mean baseline HIV viral load was 101,561 copies per milliliter. Tuberculosis was the most prevalent presenting opportunistic infection (7.7%). Stavudine, lamivudine, and nevirapine were initiated in 82% of women with the most frequent adverse drug reaction being nevirapine-associated skin rash (3.5%). Mean gestational age at HAART initiation was 27 weeks. Among women with follow-up data, 80% gained 50 or more CD4 cells per microliter and 80.5% achieved viral suppression to <1,000 copies per milliliter. Of 302 mother-infant pairs who completed postnatal follow-up, the HIV transmission rate was 5%. In women who received more than 7 weeks of HAART during pregnancy, transmission was 0.3%. CONCLUSIONS: Within the ANC ARV program, initiating pregnant women on HAART was feasible, safe, and effective. Advanced gestational age at treatment initiation and loss to follow-up emerge as important challenges in this population.  相似文献   

18.
PROBLEM : Early diagnosis of a complicated or poor pregnancy outcome in patients undergoing assisted reproductive technique (ART) fertility treatment could aid their counseling and management. A possible role for the inhibin superfamily as markers of early pregnancy viability was investigated. METHOD OF STUDY : To determine the source of the dimeric glycoproteins inhibin A (α-βA) in early pregnancy, serial blood samples from women who became pregnant following in vitro fertilization (IVF) with fresh embryo transfer (n = 50), from women who achieved pregnancy with frozen-thawed embryos (n = 8), and from a control group of women with spontaneous conceptions (n = 7) were analyzed using a two-site enzyme-linked immunosorbent assay (ELISA). Gonadotropin-releasing hormone (GnRH) analogues are routinely used in ART treatment cycles and are recognized to be luteolytic, and hence, periconceptual administration may be deleterious to pregnancy outcome. Serum samples were obtained from 8 IVF patients who conceived during the cycle in which they had inadvertent luteal phase exposure to GnRH analogues. RESULTS: Elevated serum levels of inhibin A were detected in ongoing pregnancies from 4 weeks' gestation and increased to an initial peak at 9–10 weeks' gestation. Significantly higher levels (P < 0.05) were found in the multiple pregnancies, and nonviable clinical pregnancies had very low levels of inhibin A. Inhibin pro-αC was detectable at levels above normal late luteal values in singleton and multiple pregnancies arising from IVF with fresh embryo transfer. In pregnancies established without corpus luteum activity, frozen-thaw embryo replacement, the levels of pro-αC containing inhibins were extremely low, suggesting that the corpus luteum is the major source of the alpha monomer. In pregnancies following inadvertent periconceptual exposure to GnRH analogue, the levels of pro-αC were statistically significantly higher in successful pregnancies than in early pregnancy failures. CONCLUSIONS: The feto-placental unit is confirmed as the major source of inhibin A in early pregnancy, and the initially low levels and very rapid decline in inhibin A in pregnancies with embryonic failure suggest a role for this glycoprotein as a monitor of early pregnancy viability. The corpus luteum is demonstrated to be the major source of inhibin pro-αC in early pregnancy, and very low levels in patients with peri-implantational exposure are indicative of lytic damage and herald pregnancy failure despite luteal supplementation with progesterone.  相似文献   

19.
Pregnant women infected with HIV-1 were enrolled in a prospective mother-to-infant transmission study from 1992 through 1994 in Bangkok. In participating hospitals, voluntary HIV testing was routinely offered at the beginning of antenatal care and again in the middle of the third trimester of pregnancy. Women who seroconverted to HIV during pregnancy were compared with women who had tested positive on their first antenatal test. Maternal HIV RNA levels were determined during pregnancy, at delivery, and postpartum using RNA polymerase chain reaction (PCR), and infection status in infants was determined by DNA PCR. No infants were breast-fed, but prophylactic antiretroviral therapy was not yet used in Thailand to prevent transmission from mother to infant. Among enrolled women, 16 who seroconverted during pregnancy and 279 who were HIV-1-seropositive at their first antenatal test gave birth. Median plasma RNA levels at delivery were similar for the two groups (17,505 and 20,845 copies/ml, respectively; p =.8). Two (13.3%) of 15 infants born to women who seroconverted and 66 (24.8%) of 266 infants born to previously HIV-seropositive women were infected with HIV (p =.5). There was no increased risk for mother-to-infant HIV transmission and no significant difference in viral load at delivery between HIV-infected women who seroconverted to HIV during pregnancy and those who were HIV-seropositive when first tested.  相似文献   

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