Non-disclosure to male partners and incomplete PMTCT regimens associated with higher risk of mother-to-child HIV transmission: a national survey in Kenya

Health worker experience and community support may be higher in high HIV prevalence regions than low prevalence regions, leading to improved prevention of mother-to-child HIV transmission (PMTCT) programs. We evaluated 6-week and 9-month infant HIV transmission risk (TR) in a high prevalence region and nationally. Population-proportionate-to-size sampling was used to select 141 clinics in Kenya, and mobile teams surveyed mother-infant pairs attending 6-week and 9-month immunizations. HIV DNA testing was performed on HIV-exposed infants. Among 2521 mother-infant pairs surveyed nationally, 2423 (94.7%) reported HIV testing in pregnancy or prior diagnosis, of whom 200 (7.4%) were HIV-infected and 188 infants underwent HIV testing. TR was 8.8% (4.0%–18.3%) in 6-week and 8.9% (3.2%–22.2%) in 9-month cohorts including mothers with HIV diagnosed postpartum, of which 53% of infant infections were due to previously undiagnosed mothers. Of 276 HIV-exposed infants in the Nyanza survey, TR was 1.4% (0.4%–5.3%) at 6-week and 5.1% (2.5%–9.9%) at 9-months. Overall TR was lower in Nyanza, high HIV region, than nationally (3.3% vs. 7.2%, P?=?0.02). HIV non-disclosure to male partners and incomplete ARVs were associated with TR in both surveys [aOR?=?12.8 (3.0–54.3); aOR?=?5.6 (1.2–27.4); aOR?=?4.5 (1.0–20.0), aOR?=?2.5, (0.8–8.4), respectively]. TR was lower in a high HIV prevalence region which had better ARV completion and partner HIV disclosure, possibly due to programmatic efficiencies or community/peer/partner support. Most 9-month infections were among infants of mothers without prior HIV diagnosis. Strategies to detect incident or undiagnosed maternal infections will be important to achieve PMTCT.     

福建省艾滋病患者抗病毒疗效和耐药性检测分析

目的了解我省艾滋病患者的抗病毒疗效与基因耐药性突变发生情况,为抗病毒治疗提供依据。方法采集我省25例接受抗病毒治疗的艾滋病患者外周静脉抗凝全血进行CD4+T淋巴细胞计数,分离血浆进行HIV病毒载量检测,并提取血浆标本中HIVRNA,用RT-PCR方法扩增HIVpol区蛋白酶基因全序列与部分逆转录酶序列。所得扩增片段进行序列测定后,数据运用ContigExpress编辑校正后上传至斯坦福大学HIV耐药数据库进行比对,同时运用Bio-Edit、Clustal和Mega等软件进行系统发生分析。结果本研究中的17例(68%)患者的病毒载量在1000cp/ml以下,其中40%(10例)降至检测限之下。RT-PCR获得10例患者的扩增片段。对其序列亚型测试结果表明:7例属于HIV-1AE亚型,2例HIV-1B亚型,1例为HIV-1D亚型;耐药性分析表明:10份序列对PI(蛋白酶抑制剂)药物均表现为敏感,8份序列对NRTI(核苷类逆转录酶抑制剂)及NNRTI(非核苷类逆转录酶抑制剂)表现出至少对3种药物高度耐药,最常见的突变位点为G190A、K103N和M184V,造成对NVP、3TC的高度耐药。结论目前我省艾滋病患者的抗病毒治疗取得预期效果。随着治疗时间延长,患者免疫功能也逐渐恢复,但耐药性突变发生种类和数量有所增加,出现对现有各类一线药物不同程度的耐药。为保证可持续性治疗策略的施行,需加强对抗病毒治疗患者的依从性教育,同时加强耐药性监测,及时评估治疗失败者耐药性情况,必要时提供二线药品,减少我省HIV病毒耐药株的产生与传播,保障抗病毒治疗的有效进行。     

An algorithm-based genotypic resistance score is associated with clinical outcome in HIV-1-infected adults on antiretroviral therapy

OBJECTIVES: The aim of this study was to evaluate the association between genotypic drug resistance and the occurrence of HIV-related diseases and death in HIV-1-infected adults on antiretroviral therapy. METHODS: We performed an observational study on patients from an out-patient clinic in a university hospital. Genotypic drug resistance analysis after virological treatment failure was performed in 141 patients receiving two or more antiretroviral drugs. All patients had follow up of at least 6 months after the resistance test. An algorithm was developed to estimate the level of genotypic drug resistance and to assign an actual resistance score (ARS) for the drugs prescribed to each patient. The patient population was divided into quartiles according to patients' ARS values. Our endpoint was the risk of developing an HIV-related disease [Centers for Disease Control and Prevention (CDC) category B or C] during the period starting 6 months prior to and ending 6 months after the genotypic resistance test, or death during the 6 months following the resistance test. RESULTS: There was a significant association between the level of resistance to the drugs prescribed (ARS) and our clinical endpoint: the odds ratio for an endpoint (with 95% confidence interval) was 3.20 (1.28-7.99), adjusted for CD4 cell count and HIV RNA, in patients in the highest ARS quartile compared with patients in the other three quartiles. CONCLUSIONS: Our study indicates that patients with high-level genotypic drug resistance are at increased risk of developing an HIV-related disease. This association could not be explained by differences in CD4 cell count or HIV RNA levels.     

Association between knowledge of HIV-positive status or use of antiretroviral therapy and high-risk transmission behaviors: Systematic review

To systematically review the evidence on the association between knowledge of HIV-positive status or use of antiretroviral therapy (ART) and high-risk transmission behaviors, we searched Ovid MEDLINE from 2004 to February 2012 and the Cochrane Library Database through the first quarter of 2012. Four observational studies meeting inclusion criteria addressed HIV-positive status and seven addressed the use of ART and effects on behavior. Studies including both average and high-risk populations were conducted in developed countries and were rated at least fair quality. Overall, knowledge of HIV-positive status was associated with less engagement in high-risk transmission behaviors, and the use of ART was not found to increase participation in high-risk transmission behaviors by HIV-positive individuals.     

Factors associated with virological response in HIV-infected patients failing antiretroviral therapy: a prospective cohort study

OBJECTIVES: To assess the antiviral response to optimized therapy following genotypic resistance testing and to identify factors associated with virological response in HIV-1-infected patients failing antiretroviral therapy. METHODS: A prospective cohort study was conducted in 344 HIV-1-infected patients who underwent genotypic resistance testing because of virological failure. Virological response was defined as a plasma HIV RNA level below 200 HIV-1 RNA copies/mL or a drop of plasma viral load from baseline of more than 1 log10. A multivariate logistic regression analysis was performed to identify factors associated with virological response. RESULTS: The median age of the patients was 40 years, with a male to female ratio of 4:1. Fifty-one per cent of patients had received the three major classes of antiretrovirals and the median duration of previous antiretroviral therapy was 4.6 years. At baseline, the median plasma HIV RNA level was 4.4 log10 copies/mL and the median CD4 cell count was 274 cells/microL. At 3 months, 55% of patients (188 of 344) had a virological response, which was sustained at 6 months (53%). Predictors of virological response were exposure to two or fewer protease inhibitors [odds ratio (OR) 1.8; P=0.046], and use in optimized therapy of a new class of antiretrovirals (OR 2.9; P=0.006), of more than two new drugs (OR 3.0; P<0.0001), of abacavir (OR 1.9; P=0.03), or of lopinavir/ritonavir (OR 3.7; P=0.0002). CONCLUSIONS: A high proportion of patients achieved a short-term virological response in this cohort study. Patients with the least experience of protease inhibitor treatment and in whom a new class of antiretroviral, more than two new drugs, abacavir or lopinavir/ritonavir was used in optimized therapy had the best virological outcome.     

HIV耐药评估和预防策略

HIV耐药会影响抗病毒治疗的长期疗效,使得艾滋病流行结束于2030年的目标难以实现。不同国家采用不同策略来预防和评估HIV耐药的产生和传播。目前,高收入国家对HIV感染者进行个体耐药检测。多数中低收入国家采用WHO提出的群体监测策略,监测耐药早期预警指标,评估治疗人群获得性耐药,监测治疗前耐药、传播性耐药及18月龄以下儿童耐药等措施。我国采用HIV耐药个体检测和群体监测相结合的防控策略。     

HIV treatment — a rational approach to the use of antiretroviral agents

Summary. Over the last 2 years, advances in many areas of HIV clinical research and data on the effectiveness of potent combination therapy have substantially influenced the overall perspective of long-term management of HIV disease. However, the progress against HIV also came as a result of the better understanding of HIV pathogenesis. Research work in basic science has contributed considerably to obtain a clearer picture of the mechanisms of HIV infection, mainly through the understanding of key steps in the dynamics and kinetics of viral replication in vivo. Molecular biology also revealed much about the mechanisms of HIV virulence and the emergence of drug resistance. This article will give a short overview of the most recent advances in the field.     

Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance

In 2009, a list of nonpolymorphic HIV-1 drug resistance mutations (DRMs), called surveillance DRMs (SDRMs), was created to monitor transmitted drug resistance (TDR). Since 2009, TDR increased and antiretroviral therapy (ART) practices changed. We examined the changing prevalence of SDRMs and identified candidate SDRMs defined as nonpolymorphic DRMs present on ≥ 1 expert DRM list and in ≥0.1% of ART-experienced persons. Candidate DRMs were further characterized according to their association with antiretrovirals and changing prevalence. Among NRTI-SDRMs, tenofovir-associated mutations increased in prevalence while thymidine analog mutations decreased in prevalence. Among candidate NRTI-SDRMs, there were six tenofovir-associated mutations including three which increased in prevalence (K65N, T69deletion, K70G/N/Q/T). Among candidate NNRTI-SDRMs, six that increased in prevalence were associated with rilpivirine (E138K/Q, V179L, H221Y) or doravirine (F227C/L) resistance. With the notable exceptions of I47A and I50L, most PI-SDRMs decreased in prevalence. Three candidate PI-SDRMs were accessory darunavir-resistance mutations (L10F, T74P, L89V). Adding the candidate SDRMs listed above was estimated to increase NRTI, NNRTI, and PI TDR prevalence by 0.1%, 0.3%, and 0.3%, respectively. We describe trends in the prevalence of nonpolymorphic HIV-1 DRMs in ART-experienced persons. These data should be considered in decisions regarding SDRM list updates and TDR monitoring.     

2008-2013年福建省HIV-1毒株耐药基因变异研究

目的 分析2008-2013年福建HIV-1毒株耐药基因变异情况。方法 收集2008-2013年福建省病毒载量大于1 000 copy/mL艾滋病患者,采用自建HIV-1基因型耐药检测进行耐药检测和分析。结果 共收集226例病毒载量大于1 000 copy/mL样本,平均载量值1.62×10⁵copy/mL;124例样本扩增及测序后获得蛋白酶以及部分反转录酶基因序列,亚型分析显示92例(74.2%)为CRF_01AE亚型,14例(11.3%)为B亚型,C和BC亚型各有7例,另4例为其他亚型。77对反转录酶以及蛋白酶抑制剂有不同程度耐药;对核苷类和非核苷类反转录酶抑制剂的耐药分别有63例(50.8%)和74例(59.7%),对蛋白酶抑制剂耐药9例(7.3%);核苷类反转录酶抑制剂主要耐药突变包括了M184V、M41L、D67N、L70R、T219F、K219Q等,造成对3TC、AZT、D4T等不同程度耐药;非核苷类反转录酶抑制主要耐药突变包括K101E、Y181C、K103N、G190A等,造成对NVP和EFV不同程度耐药。结论 福建省HIV-1感染者总体耐药率较低,但是随着治疗人数增加以及治疗时间延长,对反转录酶抑制剂出现较高程度耐药,仍需加强艾滋病患者耐药检测。     

AIDS in the era of antiretroviral therapy: Changes in incidence rates and predictors of AIDS among people living with HIV under clinical care in Germany,a cohort study 1999–2018

Objectives

This study examined the incidence rates and predictive utility of established prognostic factors for the progression to AIDS among people living with HIV under clinical care.

Methods

We used data from two observational cohorts of people living with HIV in Germany between 1999 and 2018. The outcome measure was the first AIDS-defining event that occurred during follow-up. Incidence rates (IRs) per 1000 person-years (PY) were calculated by years of follow-up and calendar periods. We used Cox models in our prediction analyses, including CD4 count, viral load, and age at baseline to estimate the predictive performance. Additionally, we included transmission mode to examine its predictive utility.

Results

A total of 23 299 people living with HIV were included in the analyses. Of these, 1832 developed a first AIDS event during follow-up, constituting an overall rate of 14.6/1000 PY (95% confidence interval [CI] 13.9–15.2). IRs were highest in the first year of follow-up (45.6/1000 PY, 95% CI 42.6–48.8) and then declined continuously. IRs were highest among people living with HIV who enrolled between 1999 and 2003 (36.1/1000 PY, 95% CI 32.6–40.0). A low CD4 count, high viral load, and older age at baseline increased the likelihood of progressing to AIDS. Adding transmission mode to the models did not improve the predictive performance.

Conclusions

The rates of a first AIDS event among people living with HIV have continuously declined in Germany. Health outcomes depend on a person's CD4 count, viral load, and age but not on transmission mode. To further reduce the number of AIDS cases, the focus should be on groups more likely to present in progressed stages of their HIV infection.     

18例抗病毒治疗失败儿童艾滋病患者耐药基因突变规律研究

目的对儿童艾滋病抗病毒治疗失败病例的耐药基因突变规律及特点进行研究。方法分析18例接受过高效抗逆转录病毒治疗并已经出现病毒学及免疫学失败儿童艾滋病患者的横断面临床及实验室资料,对其耐药突变结果进行分析。结果患者年龄11.6±2.4岁,治疗的时间为36±12个月,其中15例患者曾经接受过成人抗病毒药物治疗,患者的 CD4~ T 淋巴细胞为34±30个/μl(3～96个/μl),病毒载量为5.23±0.57 log10 copies/ml(4.27～6.53 log10 copies/ml)。耐药发生率为100%。对非核苷类逆转录酶抑制剂(NNRTIs)耐药突变结果分析显示:所有患者均对奈韦拉平(NVP)产生高度耐药,对依非韦伦(EFV)高度耐药的有16例。对核苷类逆转录酶抑制剂(NRTIs)耐药突变结果分析显示:对拉米夫定(LAM)高度耐药的有14例,对去羟肌苷(ddI)高度耐药的有11例,对齐多夫定(AZT)高度耐药的有14例,对司他夫定(d4T)高度耐药的有16例。重要突变位点包括 Y181C(9例)、K103N(7例)、G190A(8例)、TAMs(17例)、M184V(10例)、K65R(5例)、Q151M(2例)。结论该组治疗失败儿童患者对正在使用的 NRTIs 及 NNRTIs 均已产生高度耐药,须考虑更换新的抗病毒治疗方案。     

Maintaining the continuity of HIV-care records for patients transferring care between centers: challenges,workloads, needs and risks

With improved life expectancy, the medical records of HIV-infected patients are likely to be transferred repeatedly between HIV caregivers. The challenges, and risk for introducing medical error from incomplete record transfers are poorly understood. We measured number of requests for record transfer, the workload incurred, and explore, using genotypic antiretroviral resistance testing results (GART), the potential risk of incomplete records. Using retrospective database and chart review, we examined all patients followed at the Southern Alberta Clinic between 1 January 2004 and 1 January 2015, and determined how many patients transferred care into and out our program, the associated requests and the workload for record transfer. Using a complete record of all GART tests, the potential importance of absent historic records in current treatment decisions was analyzed. The annual churn rate was 22?±?3.4%. We received requests for only 70% of patient records who had left our care. Median time for receipt of incoming medical records was 28 days; average clerical time for processing data was 2 hours/record. Of all GART results, 25% exhibited resistance. Of 111 patients with potentially misleading GART results (i.e., documented historical resistance not visible on more recent GART), 34 (30.6%) had moved in from elsewhere. Rigorous maintenance of the continuity of the HIV record is not universally practiced. Resources, costs and logistic challenges as well as a lack of appreciation of risks clearly shown by GART testing, may be relevant barriers. Addressing such issues is pressing as aging and transfers of care are increasingly common.     

Abnormal glucose metabolism among older men with or at risk of HIV infection

OBJECTIVES: To determine factors associated with diabetes, insulin resistance, and abnormal glucose tolerance in older men with or at risk of HIV infection. METHODS: Diabetes was assessed by self-report in 643 men >or=49 years old with or at risk of HIV infection. In a subset of 216 men without previously diagnosed diabetes [including 90 HIV-uninfected men, 28 HIV-infected, antiretroviral-naive men, 28 HIV-infected men taking non-protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART), and 70 HIV-infected men taking PI-containing HAART], an oral glucose tolerance test with insulin levels was performed. HIV serology, CD4 cell count, weight, height and waist circumference were measured. Antiretroviral use, drug use, family history of diabetes, physical activity and sociodemographic data were obtained using standardized interviews. RESULTS: Of 643 participants, 116 (18%) had previously diagnosed diabetes. With the oral glucose tolerance test, 15 of 216 men (7%) were found to have undiagnosed diabetes and 40 (18%) impaired glucose tolerance. Factors independently associated with previously diagnosed diabetes included use of non-PI-containing HAART, methadone treatment, positive CAGE test for alcoholism, obesity and family history of diabetes. Factors independently associated with greater insulin resistance included waist circumference and heroin use. Factors independently associated with abnormal glucose tolerance (impaired glucose tolerance or diabetes) included age >or=55 years and Hispanic ethnicity. CONCLUSIONS: HIV-infected men with diabetes risk factors should undergo screening for diabetes regardless of HAART use. Interventions targeting modifiable risk factors, including overweight and physical inactivity, are warranted. The potential impact of opiate and alcohol abuse on glucose metabolism should be recognized in clinical care, and addressed in future research studies of HIV-infected persons.