Emergence of antiretroviral resistance in HIV-positive women receiving combination antiretroviral therapy in pregnancy

BACKGROUND: Antenatal antiretroviral therapy is integral to preventing vertical transmission of HIV-1. The impact of temporary triple antiretroviral therapy in pregnancy on the emergence of antiretroviral resistance has not been studied. OBJECTIVE: To determine the impact of temporary triple antiretroviral therapy in pregnancy on emergence of antiretroviral resistance. METHODS: Pregnant HIV-1 infected women with a pre-treatment CD4 cell count >300 x 10(6)/l initiated triple antiretroviral therapy in the third trimester and discontinued postpartum. Genotypic resistance testing was performed after antiretroviral cessation and on pretreatment samples when postpartum samples showed primary mutations. RESULTS: In a cohort of 50 women who initiated antiretroviral therapy in pregnancy, 39 (78%) had postpartum HIV-1 nucleotide sequences available for analysis: 35 of these (90%) were previously antiretroviral naive. Seven primary mutations, V106A (one), Y181C (two), G190A (one), K101E (one), M184V (one), T215S (one) were detected in five (13%) women. All five were on regimens that included nevirapine and all were antiretroviral therapy naive prior to the index pregnancy. Four had no mutations detected pretreatment (one did not have a pretreatment analysis available; viral load 83 copies/ml). The median duration of antiretroviral exposure was 70 days. CONCLUSION: Emergence of genotypic resistance is significant in this cohort of pregnant women. All mutations detected were in those that took nevirapine-containing regimens. The clinical implications of these mutations are unknown.     

妊娠合并HBV感染对母婴结局的影响

目的　探讨妊娠合并HBV感染对母婴结局的影响。方法　选取2016年3月—2018年7月我院收治的妊娠合并HBV感染孕妇86例为观察组,另选取同时期在医院进行孕检的健康孕妇128例为对照组。对比2组妊娠期高血压、胎膜早破、早产、剖宫产、产后出血发生率,并对比2组孕妇分娩的新生儿结局等。结果　观察组妊娠期高血压、胎膜早破、早产、剖宫产、产后出血的发生率分别为10.47%、17.44%、6.98%、34.88%、16.28%,显著高于对照组（P均＜0.05）;观察组胎儿窘迫、死胎、新生儿窒息、低体质量儿发生率分别为11.63%、6.98%、13.95%、20.93%,显著高于对照组（P均＜0.05）;86例妊娠合并HBV感染孕妇中发生妊娠期并发症50例（并发症组）,未发生妊娠期并发症36例（无并发症组）。并发症组的TBIL、AST、ALT水平均明显高于无并发症组（P均＜0.05）;并发症组整体HBV DNA载量高于无并发症组（P＜0.05）。结论　妊娠期合并HBV感染会产生不良母婴结局,肝功能异常及HBV DNA载量均是导致不良母婴结局的重要因素,对于此类孕妇临床应注重产前肝功能的检测,及时给予阻断治疗,尽可能改善母婴结局。     

Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy

BACKGROUND: Immune restoration following combination antiretroviral therapy (cART) questions the maintenance of prophylaxis among HIV-infected patients with cryptococcosis. OBJECTIVE: To describe the long-term outcome after the diagnosis of cryptococcosis at the cART era. DESIGN: Multicentre cohort of patients with a diagnosis of cryptococcosis between 1996 and 2000, follow-up until December 2002. Comparison with a historical cohort (1990-1994) for survival. SETTING: Eighty-four French AIDS clinical centres. PATIENTS: Two-hundred and forty HIV-infected adult patients at the cART era and 149 at the pre-cART era experiencing a first episode of culture-confirmed cryptococcosis. RESULTS: In the cART era, 82/189 patients surviving more than 3 months after initiation of antifungal therapy had their maintenance therapy interrupted with a subsequent median follow-up of 19 months. Their relapse rate per 100 person-years was 0.9 [95% confidence interval (CI),0.0-2.0]. When considering the whole cART cohort, probability of reaching negative serum cryptococcal antigen was 71% after 48 months of follow-up. A CD4 cell count < 100/microl [relative risk (RR), 5.5; 95% CI, 1.3-22.2], antifungal therapy < 3 months over the past 6 months [RR, 5.0; 95% CI, 1.1-22.3] and serum cryptococcal antigen titre > or = 1/512 [RR, 3.5; 95% CI, 1.1-10.8] were associated with a higher rate of cryptococcosis relapse. The mortality rate per 100 person-years was 15.3 [95% CI,12.2-18.4] in the cART era versus 63.8 [95% CI,53.0-74.9] in the pre-cART era although early mortality did not differ between the two periods. CONCLUSION: Overall survival after cryptococcosis has dramatically improved at the cART era. Immune restoration and low serum cryptococcal antigen titres are associated with lower cryptococcosis relapse rates.     

Maternal hepatotoxicity with nevirapine as part of combination antiretroviral therapy in pregnancy

OBJECTIVES: To describe the maternal tolerability of nevirapine as part of combination antiretroviral therapy in pregnancy at three HIV centres in Dublin, Ireland and to determine risk factors for development of significant hepatotoxicity. METHODS: A retrospective study was carried out of all women prescribed nevirapine as part of combination antiretroviral therapy in pregnancy at three HIV centres in Dublin, Ireland (October 2000 to February 2003). Toxicities experienced were graded according to the Division of AIDS toxicity guidelines for adults. Statistical analysis was performed to determine whether there were differences between those that did and those that did not experience significant hepatotoxicity. RESULTS: A total of 123 women initiated nevirapine as part of combination antiretroviral therapy in the study period. Eight women developed significant hepatotoxicity, including two women who died from fulminant hepatitis. Women who experienced more severe hepatotoxicity had higher pretreatment CD4 counts (P=0.01). CONCLUSIONS: In this cohort, women who experienced more severe hepatotoxicity had higher pretreatment CD4 counts, lending additional weight to the need for caution in using nevirapine as part of combination antiretroviral therapy in women not requiring antiretroviral therapy for their own health.     

Nucleoside combinations for antiretroviral therapy: efficacy of stavudine in combination with either didanosine or lamivudine

This paper reviews the results of three trials, HIV NAT002, AI455-053, and AIDS Clinical Trials Group (ACTG) 306, all of which evaluated the effectiveness of stavudine (d4T)-containing two-nucleoside combinations in antiretroviral-naive patients with human immunodeficiency virus type 1 (HIV-1) infection. The latter two studies directly compared d4T plus didanosine (ddI) or lamivudine (3TC) versus zidovudine (ZDV) plus each of these two nucleosides. The combined results of the three trials support the conclusion that d4T can be used effectively in combination with either ddI or 3TC to reduce viral loads and increase CD4 cell counts in patients with HIV-1 infection. The results of AI455-053 and ACTG 306 show further that combination of d4T with either ddI or 3TC is at least as effective as the use of ZDV with these nucleosides.     

Adherence to antiretroviral therapy in pregnancy

Successful interventions to prevent congenital HIV require adherence to highly active antiretroviral therapy (HAART) in pregnancy from mothers and agreement with other interventions including mode of delivery and infant testing. We sought to audit adherence support offered antenatally, adherence with HAART, recommendations for delivery and infant testing in women receiving HIV care at our unit and delivering a child in 2004 and 2005. Of the 32 women identified, an adherence discussion was conducted when commencing therapy in 87% and subsequent visits in 77%. Five women were non-adherent with HAART, one disagreed with recommendations for delivery, and attendance at initial post-natal tests was documented in 61%. In general, the British HIV Association guidelines with regard to adherence are followed. Although numbers in this cohort are small, age, ethnicity and pre-pregnancy HIV diagnosis did not seem to affect adherence, but being therapy na?ve and poor adherence may predict non-attendance at infant follow-up.     

Once weekly exenatide: efficacy,tolerability and place in therapy

Exenatide once weekly is the first glucose‐lowering agent available to patients with type 2 diabetes mellitus (T2DM) which is administered once per week. This long‐acting formulation contains the same active ingredient as exenatide twice daily, except that the exenatide is encapsulated in dissolvable microspheres. Following subcutaneous injection, exenatide once weekly microspheres remain in place under the skin and slowly degrade, releasing active exenatide continuously into circulation. In randomized clinical trials, exenatide once weekly was associated with significant glycaemic improvement and moderate weight loss in patients with T2DM when administered as monotherapy or in combination with a variety of oral antidiabetic agents. Exenatide once weekly also lowered blood glucose more effectively than titrated basal insulin in patients on metformin or metformin plus sulphonylurea background therapy. Gastrointestinal side effects (nausea, vomiting and diarrhoea) were the most common tolerability issues associated with exenatide once weekly administration, but they occurred at lower rates than in patients on other glucagon‐like peptide receptor agonists (i.e., exenatide twice daily or liraglutide). Issues regarding the place of exenatide once weekly in T2DM pharmacotherapy are discussed.     

Older age and the response to and tolerability of antiretroviral therapy

BACKGROUND: The unique health needs of a growing older adult population infected with human immunodeficiency virus (HIV) require study, especially in terms of the response to and tolerability of highly active antiretroviral therapy (HAART). METHODS: Changes in HIV clinical markers after HAART initiation were compared among 2259 patients aged 18 to 39 years (reference group), 1834 patients aged 40 to 49 years, and 997 patients 50 years or older enrolled in an integrated health care system. RESULTS: Patients 50 years or older were more likely to achieve HIV RNA levels of less than 500 copies/mL within 1 year of HAART initiation (hazard ratio [HR], 1.15; P =.009), but adjustment for adherence attenuated this finding (HR, 1.03; P =.59). Subsequent HIV RNA level rebound (to > or =1000 copies/mL) was less likely among patients aged 40 to 49 years (HR, 0.81; P =.01), which persisted after adjustment for adherence (HR, 0.79; P =.004). In year 1 of HAART, younger patients had larger CD4 T-cell count increases (131.8, 121.3, and 111.8 CD4 T cells/microL per year among patients aged 18-39, 40-49, and > or =50 years, respectively; P =.046). In years 2 through 6, older patients had larger CD4 T-cell count increases (4.5, 11.6, and 9.7 CD4 T cells/microL per year among patients aged 18-39, 40-49, and > or =50 years, respectively; P =.04). After adjustment for adherence, age differences in CD4 T-cell count changes remained in year 1 (P =.02) but not in years 2 through 6 (P =.08). Other factors, including comorbidities, had no effect on study results. Metabolic (glucose and lipids), hematologic (absolute neutrophils and hemoglobin), and renal (creatinine) abnormalities were more likely among older patients. CONCLUSION: Despite a higher risk of adverse events, patients 50 years or older sustained high therapy adherence to maintain improved virological outcomes and to compensate for their early blunted CD4 T-cell count response compared with younger patients.     

抗反转录病毒治疗时机选择对妊娠合并HIV感染者妊娠结局影响的研究

目的研究抗反转录病毒治疗时机选择,明确其对妊娠合并HIV感染者妊娠结局的影响。方法选取2015年1月—2018年1月我院收治的103例妊娠合并HIV感染者作为研究对象,根据抗反转录病毒治疗时机不同分为2组,其中在孕28周以内行抗反转录病毒治疗的患者作为研究组(n=74例);在孕28周及以后行抗反转录病毒治疗,且至分娩间隔时间不少于1个月的患者作为对照组(n=29例)。观察2组患者抗病毒治疗效果、妊娠结局及18月龄儿HIV感染随访情况。结果行抗反转录病毒治疗后,分娩前1 d研究组患者病毒载量下降幅度大于对照组(P<0.05);研究组患者早产比例为2.70%,显著低于对照组(P<0.05)。结论妊娠合并HIV感染者尽早实施抗反转录病毒治疗对于降低母体病毒载量和胎儿早产率具有重要意义。