两种非核苷类逆转录酶抑制剂治疗艾滋病的不良反应分析

目的 了解艾滋病患者接受两种非核苷类逆转录酶抑制剂进行抗逆转录病毒治疗发生不良反应的情况.方法 回顾性分析2015年6月至2016年6月在武汉大学中南医院就诊的126例使用依非韦伦(E-FV)和150例使用奈韦拉平(NVP)进行联合抗逆转录病毒治疗的艾滋病患者的临床资料,统计不良反应发生率.结果 EFV组的总体不良反应发生率为87.3％(110/126),高于NVP组的44.0％(66/150),差异有统计学意义(x2=55.573,P＜0.01).EFV组不良反应以头晕多梦(64.3％,81例)和皮疹(9.5％,12例)为主,NVP组以皮疹(18.0％,27例)和肝损害(16.7％,25例)为主;但EFV组患者出现精神障碍4例(其中2例自杀死亡),癫痫1例,男性乳腺增生3例,NVP组则未见.EFV组83.6％(92例)和NVP组74.2％(49例)的不良反应发生在用药的前6周内;且前者69.1％(76例)可逐渐耐受,而后者仅4.5％(3例),差异有统计学意义(x2=69.468,P＜0.01),但NVP组停药或换药后90.9％(60例)的患者不良反应消失.结论 EFV和NVP的不良反应各具特点,前者以早期轻微的神经系统症状为主,且能逐渐耐受,后者以早中期出现的皮疹和肝损害为主,常需停药或换药得以恢复.临床上对于EFV相关的精神障碍宜早期进行干预,以免发生意外.     

Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors

A series of new 5-alkyl-2-benzylsulfanylpyrimidin-4(3H)-ones (5a-y) bearing different substituted arylmethyl moieties at the C-6 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against HIV-1 and HIV-2 in MT-4 cell cultures. The majority of the title compounds showed moderate to good activities against HIV-1 with an IC(50) range from 6.67 microM to 0.12 microM. Among them, 6-(3,5-dimethylbenzyl) analogue 5q exhibited the most potent anti-HIV-1 activity (IC(50)=0.12 microM, SI>2642), which was about 40-fold more active than the reference compounds 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine (HEPT) and 2',3'-dideoxyinosine (DDI). The structure-activity relationships (SARs) of these new congeners were further discussed.     

Severe malnutrition and metabolic complications of HIV-infected children in the antiretroviral era: clinical care and management in resource-limited settings

More than 2 million children globally are living with HIV infection and >90% of these reside in sub-Saharan Africa. Severe acute malnutrition (SAM) remains a major problem for HIV-infected children who live in resource-limited settings (RLS), and SAM is an important risk factor for mortality. SAM in HIV-infected children is associated with complications including electrolyte disorders, micronutrient deficiencies, and severe infections, which contribute to the high mortality. Access to antiretroviral therapy (ART) has significantly improved the survival of HIV-infected children, although the response to ART of children with SAM remains undocumented in the literature. Immune and virologic responses to ART in RLS are similar to those of infected children in resource-rich settings, but delays in initiation of therapy have led to a high early mortality. Antiretroviral drug toxicities have been described in children who receive therapy and may affect their quality of life and long-term survival. Metabolic complications of ART include lipodystrophy, dyslipidemia, lactic acidosis, insulin resistance, and osteopenia. These complications have been well described in adults and children from developed countries, but data from RLS are limited, and these complications may be compounded by SAM. In this article we review the epidemiology, clinical presentation, and complications of SAM in HIV-infected children and the metabolic complications of HIV-infected children in the era of ART, and discuss future research priorities for RLS.     

Synthesis and anti-HIV activity evaluation of 2-(4-(naphthalen-2-yl)-1,2,3-thiadiazol-5-ylthio)-N-acetamides as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

A series of 2-(4-(naphthalen-2-yl)-1,2,3-thiadiazol-5-ylthio)acetamide (TTA) derivatives were synthesized and evaluated as potent inhibitors of HIV-1. Among the newly disclosed TTAs, compounds 7f, 7g and 7c were the most potent inhibitors of HIV-1 replication of the series (EC₅₀ = 0.17 ± 0.02, 0.36 ± 0.19 and 0.39 ± 0.05 μM, respectively), coupled with a reasonable selectivity index (SI > 1452, >845, and >774, respectively). They possess improved or similar HIV-1 inhibitory activity compared with NVP (EC₅₀ = 0.208 μM) and DLV (EC₅₀ = 0.320 μM). The preliminary structure–activity relationships among the newly synthesized congeners are discussed briefly and rationalized by docking studies.     

Synthesis and anti-HIV activity evaluation of 1-[(alkenyl or alkynyl or alkyloxy)methyl]-5-alkyl-6-(1-naphthoyl)-2,4-pyrimidinediones as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

The synthesis and anti-HIV activity evaluation of a new series of 2,4-pyrimidinediones bearing a 6-(1-naphthoyl) group are described. In general, it was found that most of the title compounds showed good activities against human immunodeficiency virus type-1 (HIV-1). In particular, compound 26 displayed the most potent anti-HIV-1 activity (IC(50)=0.11+/-0.05 microM), inhibiting HIV-1 replication in MT-4 cells more effectively than HEPT (by 45-fold) and DDI (by 50-fold).     

Postpartum contraceptive preferences of HIV-infected women in the era of highly active antiretroviral therapy (HAART) and scheduled cesarean deliveries

Background

We sought to determine if postpartum tubal ligation among HIV-infected women changed with the introduction of highly active antiretroviral therapy (HAART) and scheduled cesarean delivery.

Methods

Retrospective cohort study of HIV-infected women delivered before (Pre-HAART) and after (Post-HAART) the introduction of HAART and scheduled cesarean delivery. Rates of the primary outcome, postpartum tubal ligation (PPTL), were compared by univariable and multivariable analyses.

Results

We found that 34.5% (60/174) of women in the Post-HAART period chose PPTL, compared to 22.0% (18/82) in the Pre-HAART period [unadjusted OR=1.87 (95% CI 1.02–3.44), p=.04]. When stratified by mode of delivery, rates of PPTL were not significantly different between the two periods. Similarly, in multivariable analysis controlling for confounders, rates of PPTL were not different between the two periods [adjusted OR=1.40 (95% CI=0.66–2.99), p=.39].

Conclusions

HIV-infected women on HAART are overall more likely to have PPTL, but cesarean delivery appears to be the facilitator of this choice.     

Measuring the health-related quality of life (HRQoL) of young children in resource-limited settings: a review of existing measures

Purpose

This review sought to identify and summarize the instruments adapted or developed for measuring HRQoL among young children (<8 years) living in resource-limited settings.

Methods

A review of the literature was conducted in two phases. Phase one searched the PubMed, PsycInfo, Web of Knowledge (Web of Science), African Index Medicus, and SocINDEX databases and identified widely used child HRQoL instruments. Phase two reviewed the articles using the selected HRQoL instruments and extracted information on their use in resource-limited settings including adaption processes.

Results

Seven instruments were identified that measured the HRQoL of young children. Six had been used in resource-limited settings. Of the 452 articles using these instruments, a total of 23 (5 %) studies used one of the identified HRQoL instruments in a resource-limited setting. Among these studies, 39 % employed an adaptation process for the use of that instrument. No instruments had been developed specifically for measuring the HRQoL of young children in resource-limited settings.

Conclusions

If pediatric HRQoL instruments are to be used in resource-limited settings, it is critical that they be developed and adequately adapted to those settings. Only then will interventions lead to larger increases in the overall HRQoL and well-being of children.     

Impact of protease inhibitors and other antiretroviral treatments on acquired immunodeficiency syndrome survival in San Francisco, California, 1987-1996

The authors assessed temporal trends in acquired immunodeficiency syndrome (AIDS) survival for 15,271 persons in San Francisco, California, diagnosed between 1987 and 1996 with an opportunistic illness included in the 1987 AIDS case definition. Predictors of survival were evaluated for 5,686 persons who were diagnosed between 1993 and 1996 and met the 1993 AIDS case definition. Median survival was 19 months for persons diagnosed between 1987 and 1989, 17 months for persons diagnosed between 1990 and 1992, 15 months for persons diagnosed between 1993 and 1994, and 31 months for persons diagnosed between 1995 and 1996. Decreased mortality was associated with use of antiretroviral therapy without protease inhibitors before AIDS (relative hazard (RH) = 0.88, 95% confidence interval (CI): 0.8, 1.0) and after AIDS (RH = 0.83, 95% CI: 0.7, 0.9) and use of antiretroviral agents with protease inhibitors before AIDS (RH = 0.25, 95% CI: 0.2, 0.3) and after AIDS (RH = 0.36, 95% CI: 0.3, 0.4). Increased mortality was found for persons aged > or = 40 years (RH = 1.43, 95% CI: 1.3, 1.6), persons initially diagnosed with an opportunistic illness (RH = 1.97, 95% CI: 1.8, 2.2), and homosexual injection drug users (RH = 1.33, 95% CI: 1.2, 1.5). Survival after AIDS has increased. Treatment with antiretroviral agents, particularly protease inhibitors, strongly predicts improved survival.     

Gender distribution of adult patients on highly active antiretroviral therapy (HAART) in Southern Africa: a systematic review

Background  

HIV and AIDS are significant and growing public health concerns in southern Africa. The majority of countries in the region have national adult HIV prevalence estimates exceeding 10 percent. The increasing availability of highly active antiretroviral therapy (HAART) has potential to mitigate the situation. There is however concern that women may experience more barriers in accessing treatment programs than men.     

The influence of technical products on sexual activity and gender relations: oral contraceptive, condom, oral treatments of sexual disorders

Over the past fifty years, sexuality has been marked by an increasing interest in sexual and reproductive health. This progression can be seen in changes in legislation, in social norms, in sexual practices and in gender relations. It is also characterised by the introduction and use of various technical products, which have a direct impact on both sexual activity and its consequences: contraception, methods of sexually transmissible infections prevention and treatment for male impotence. Irrespective of their usefulness or their technical effectiveness, these different products are endowed with a symbolic identity that reflects dominant representations of sexuality and the sexual roles of men and women. An analysis of the way in which these products are used illustrates how they have contributed to the development of scenarios of sexual relations, by distributing specific roles to men and to women. Three models of sexuality associated with each product have been analysed: liberated sexuality, protected sexuality, and functional sexuality.