Initial Antiretroviral Treatment Research Articles

Therapeutic effectiveness on early and delayed treatment of antiretroviral in TB-HIV patients: a literature review

Introduction: Indonesia is one of the countries with a high TB-HIV prevalence. Antiretroviral treatment (ART) is only being administered to approximately 42% of TB-HIV patients. The low utilization of ART can be attributed, in part, to the delayed initiation of treatment. Nonetheless, starting ART in these people at an early stage poses risks, owing to the increased likelihood of drug-drug interactions and the manifestation of Immune Reconstitution Inflammatory Syndrome (IRIS) side effects when combined with anti-TB medication. Postponing ART, on the other hand, can hasten illness progression and increase the risk of death. Methods: A literature review was conducted to assess the effects of early ART (within four weeks of getting anti-TB) against delayed ART initiation (at least eight weeks after receiving anti-TB) in individuals co-infected with TB and HIV. The data was obtained by a comprehensive electronic search using the PubMed and Science Direct databases. Results: The findings of our study suggest that there was no statistically significant disparity in mortality rates between the early ART group and the delayed ART group. The initial ART cohort had a markedly elevated susceptibility to encountering an IRIS occurrence, particularly among individuals with a CD4 count below 50 cells per cubic millimeter. Conclusion: In summary, the strategy of delaying the initiation of ART in patients co-infected with TB-HIV is seen as preferable when compared to the approach of early treatment. The frequency of IRIS events is a significant determinant in determining the optimal timing of ART initiation in individuals co-infected with TB-HIV.

Predictors of low-level HIV viraemia and virological failure in the era of integrase inhibitors: A Spanish nationwide cohort.

To pinpoint factors associated with low-level viraemia (LLV) and virological failure (VF) in people living with HIV in the era of high-efficacy antiretroviral treatment (ART) and widespread use of integrase strand transfer inhibitor (INSTIs)-based ART. We included adults aged >18years starting their first ART between 2015 and 2018 in the Spanish HIV/AIDS Research Network National Cohort (CoRIS). Low-level viraemia was defined as plasma viral load (pVL) of 50-199 copies/mL at weeks 48 and 72 and VF was defined as pVL ≥50 copies/mL at week 48 and pVL ≥200 copies/mL at week 72. Multivariable logistic regression models assessed the impact on LLV and VF of baseline CD4 T-cell count, CD4/CD8 T-cell ratio and pVL, initial ART classes, age at ART initiation, time between HIV diagnosis and ART initiation, gender and transmission route. Out of 4186 participants, 3120 (76.0%) started INSTIs, 455 (11.1%) started boosted protease inhibitors (bPIs) and 443 (10.8%) started nonnucleoside reverse transcriptase inhibitors (NNRTIs), either of them with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Low-level viraemia was met in 2.5% of participants and VF in 4.3%. There were no significant differences throughout the years for both virological outcomes. Baseline HIV-1 RNA >5log10 copies/mL was the only consistent predictor of higher risk of LLV [adjusted odds ratio (aOR) = 9.8, 95% confidence interval (CI): 2.0-48.3] and VF (aOR = 5.4, 95%CI: 1.9-15.1), even in participants treated with INSTIs. The rates of LLV and VF were low but remained steady throughout the years. Baseline HIV-1 RNA >5log10 copies/mL showed a persistent association with LLV and VF even in participants receiving INSTIs.

Moving Toward a Functional Cure for HIV-1

Abstract Despite the recent success of suppressing human immunodeficiency virus 1 (HIV-1) replication in the peripheral blood with antiretroviral therapy, elimination of the provirus from infected cells remains challenging because the virus can integrate into the host genome and become a latent proviral reservoir. The removal of these latent viral reservoirs from tissue containing infected resting memory CD4+ T cells remains a major barrier to developing a cure for HIV-1. Several novel strategies have recently been developed for curing HIV infection. These include stem cell transplantation with CCR5-Δ32 mutated cells, initial antiretroviral treatment in the very early stage of HIV infection, gene editing to excise the HIV genome or generate CCR5-mutated HIV-1-resistant cells, “shock-and-kill” to reactivate latent HIV using latency reversal agents combined with enhanced immune clearance methods, and an emerging “block-and-lock” strategy to reactivate latent HIV using latency reversal agents combined with enhanced immune clearance methods. However, the high risks and limitations to scale-up in clinics, as well as poor performance in clinical trials, have hampered these efforts. This review aims to describe the present efforts that are being made to combat HIV latency, and critically discuss the limitations and future of the cure for HIV-1.

Enhanced Immunological Recovery With Early Start of Antiretroviral Therapy During Acute or Early HIV Infection-Results of Italian Network of ACuTe HIV InfectiON (INACTION) Retrospective Study.

Background:Viral load peak and immune activation occur shortly after exposure during acute or early HIV infection (AEHI). We aimed to define the benefit of early start of antiretroviral treatment (ART) during AEHI in terms of immunological recovery, virological suppression, and treatment discontinuation.Setting:Patients diagnosed with AEHI (Fiebig stages I-V) during 2008-2014 from an analysis of 20 Italian centers.Methods:This was an observational, retrospective, and multicenter study. We investigated the effect of early ART (defined as initiation within 3 months from AEHI diagnosis) on time to virological suppression, optimal immunological recovery (defined as CD4 count ≥500/µL, CD4 ≥30%, and CD4/CD8 ≥1), and first-line ART regimen discontinuation by Cox regression analysis.Results:There were 321 patients with AEHI included in the study (82.9% in Fiebig stage III-V). At diagnosis, the median viral load was 5.67 log10 copies/mL and the median CD4 count was 456 cells/µL. Overall, 70.6% of patients started early ART (median time from HIV diagnosis to ART initiation 12 days, IQR 6-27). Higher baseline viral load and AEHI diagnosis during 2012-2014 were independently associated with early ART. HBV co-infection, baseline CD4/CD8 ≥1, lower baseline HIV-RNA, and AEHI diagnosis in recent years (2012-2014) were independently associated with a shorter time to virological suppression. Early ART emerged as an independent predictor of optimal immunological recovery after adjustment for baseline CD4 (absolute and percentage count) and CD4/CD8 ratio. The only independent predictor of first-line ART discontinuation was an initial ART regimen including > 3 drugs.Conclusions:In a large cohort of well-characterized patients with AEHI, we confirmed the beneficial role of early ART on CD4+ T-cell recovery and on rates of CD4/CD8 ratio normalization. Moreover, we recognized baseline CD4/CD8 ratio as an independent factor influencing time to virological response in the setting of AEHI, thus giving new insights into research of immunological markers associated with virological control.

Efficacy and Tolerability of Lopinavir/Ritonavir- and Efavirenz-Based Initial Antiretroviral Therapy in HIV-1-Infected Patients in a Tertiary Care Hospital in Beijing, China.

Background: Lopinavir/ritonavir (LPV/r) is a major antiretroviral treatment in China, but little is known about the performance of first-line LPV/r-based regimen in treatment-naïve patients with human immunodeficiency virus type 1 (HIV-1) infection. This study aims to assess the efficacy and adverse effect events of LPV/r plus lamivudine and tenofovir or zidovudine as an initial antiretroviral treatment in HIV-1-infected individuals for whom cannot take efavirenz (EFV) or is allergic to EFV.Methods: We performed a retrospective study of patients registering with the China’s National Free Antiretroviral Treatment Program from July 2012 to January 2017, followed at a tertiary care hospital in Beijing, China. The primary outcome was the proportion of subjects with HIV-1 RNA ≤40 copies/ml at 6 and 24 months of treatment. We assessed the immunological response and adverse events.Results: In total, 4,862 patients were enrolled in the study and 237 were eligible for analysis in each study arm. During the first six months, virological suppression was better with the LPV/r-based regimen than with the EFV-based regimen (93.80 vs 87.80% for P < 0.05). Viral suppression rates continued to increase until 12 months, remain steady thereafter until 24 months, for both groups. The multilevel analysis revealed that patients in the LPV/r group were more likely to display improvements in CD4 T-cell count over time than those in the EFV group (P < 0.001). Grade 3 or 4 laboratory adverse events were observed in 14 patients (5.91%) from the LPV/r group and three patients (1.20%) in EFV group.Conclusion: Our findings demonstrate that LPV/r-containing regimens are effective and well-tolerated in Chinese treatment-naïve patients with HIV-1 infection.

Death and attrition among HIV–infected persons receiving initial antiretroviral treatment in Xichang, Sichuan, 2008–2018

Objective To understand the death and attrition and influencing factors among HIV–infected persons receiving initial antiretroviral therapy(ART) in Xichang City, Sichuan Province during 2008–2018. Methods Retrospective cohort research was adopted to analyze the death and attrition among HIV–infected persons receiving initial ART in Xichang City, Sichuan Province, 2008–2018. Data were collected through national AIDS comprehensive treatment and prevention system. Cox proportional hazard regression model was employed to analyze related factors of death and attrition. Results A total of 2 723 eligible HIV–infected persons were enrolled. The mortality and ART attrition rates among all patients were 1.92 deaths and 2.49 attritions per 100 person–years, respectively. The mortality and attrition rates were 10.83 and 13.89 per 100 person–years in the first year of ART. Cox regression analysis showed that the main risk factors of mortality were aged ≥ forty years ( HR =2.30, 95% CI : 1.53–3.48), males ( HR =1.94, 95% CI : 1.14–3.30), tuberculosis infection one year before ART ( HR =1.92, 95% CI : 1.01–3.65), AIDS–related disease/symptom three months before ART ( HR =2.44, 95% CI : 1.50–3.99), hepatitis B infection before ART ( HR =2.50, 95% CI : 1.32–4.71) and less than 200 cells/uL of CD4 + T lymphocyte counts ( HR =1.79, 95% CI : 1.12–2.86) at the initiation of ART. And the main risk factors of attrition were aged ≥ forty years ( HR =1.53, 95% CI : 1.07–2.18), males ( HR =5.60, 95% CI : 2.60–12.08), injection drug users ( HR =2.18, 95% CI : 1.46–3.27) and initial ART regimen EFV+3TC+TDF ( HR =2.57, 95% CI : 1.32–5.01). Conclusion The effect of antiretroviral treatment was remarkable among HIV–infected persons in Xichang City. But the mortality and ART attrition rate in the first year were high. Targeted measures should be taken and focus on reducing the attrition among injection drug users after releasing from prison, so as to improve the effect of antiretroviral treatment. 摘要： 目的 了解四川省西昌市2008－2018年初始抗病毒治疗HIV感染者死亡和脱失的情况及其影响因素。 方法 采用回顾性队列研究的方法, 从艾滋病基本防治信息系统选取2008－2018年在西昌市首次开始抗病毒治疗 (ART) 的HIV感染者, 分析抗病毒治疗者的死亡和脱失情况。采用Cox比例风险回归模型对影响抗病毒治疗HIV感染者病死率和脱失率的相关因素进行分析。 结果 共计2 723例HIV感染者进入队列, 总体病死率为1.92/100人年, 总体脱失率为2.49/100人年。在开始抗病毒治疗的第1年内病死率和脱失率分别为10.83/100人年、13.89/100人年。Cox 回归分析结果显示接受抗病毒治疗患者主要的死亡风险是年龄≥40岁 ( HR =2.30, 95% CI ：1.53~3.48) 、男性 ( HR =1.94, 95% CI ：1.14~3.30) 、ART前一年内结核感染 ( HR =1.92, 95% CI ：1.01~3.65) 、ART前三个月出现艾滋病相关疾病/症状 ( HR =2.44, 95% CI ：1.50~3.99) 、ART前乙肝感染 ( HR =2.50, 95% CI ：1.32~4.71) 、CD4+T淋巴细胞计数< 200 cells/ul ( HR =1.79, 95% CI ：1.12~2.86) 。接受抗病毒治疗患者主要的脱失风险是年龄≥40岁 ( HR =1.53, 95% CI ：1.07~2.18) 、男性 ( HR =5.60, 95% CI ：2.60~12.08) 、静脉吸毒 ( HR =2.18, 95% CI ：1.46~3.27) 、初始抗病毒治疗方案为EFV+3TC+TDF ( HR =2.57, 95% CI ：1.32~5.01) 。 结论 西昌市HIV感染者的抗病毒治疗效果显著, 但在开始治疗的第1年内病死率和脱失率较高。抗病毒治疗工作需采取针对性的措施, 重点要减少静脉吸毒人群刑满释放后的脱失, 从而提高抗病毒治疗效果。

Reasons for Antiretroviral Treatment Change Among Adult HIVAIDS Patients at Nedjo General Hospital, Western Ethiopia

Background:Frequent change of Antiretroviral Treatment (ART) regimen is a challenging problem especially in a resource-limited setting like Ethiopia where treatment options are limited. This study was aimed to identify reasons for ART regimen change among adult HIV patients at Nedjo General Hospital (NGH).Methods:An institutional-based retrospective cross-sectional study was conducted at NGH by reviewing patient information cards from 2006 to 2016.Results:From a total of 117 included patients, 50.4% were females and the median (IQR) age of the patients was 28 (24-47) years. Majority of patients, 63 (53.9%) started their treatment at world health organization (WHO) clinical stage III (53.9%) and CD4 count of between 200-350 cells/mm3 (44.54%). At the beginning of ART, 56 (47.9%) patients were on a fixed-dose combination of stavudine-lamivudine-nevirapine (D4T/3TC/NVP). The single-drug substitutions were D4T (n = 63), NVP (n = 34), AZT (n =5), EFV (n = 2), and TDF (n = 1). Majority of the patients, 35(29.9%) switched their initial ART regimen after 3 years of regimen commencement. The common reasons reported for initial regimen change was availability of new drug 46 (39.3%) followed by toxicity/side effects 34 (29.2%). From all toxicities, peripheral neuropathy (47.1%) was the most common toxicity followed by rash (20.6%). After regimen change, 47 (40.2%) were received AZT+3TC+NVP.Conclusion:Availability of new drug and toxicity were the common reasons for regimen modifications. There should be updated guidelines, sustainable supply of affordable ART drugs, and effective laboratory materials to increase treatment success and minimize the toxicity of the drugs.

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors.

BackgroundWe aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen.MethodsWe analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen.ResultsAmong 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%).Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4<200 cells/μL and HIV-RNA>100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4<200 cells/μL and HIV-RNA>100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//μL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014–2015 to 2016–2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals’ location.ConclusionsThe choice of initial ART regimens is consistent with Spanish guidelines’ recommendations, but is also clearly influenced by physician’s perception based on patient’s clinical and sociodemographic variables and by the prescribing hospital location.

Effects of rilpivirine, 17\u03b2-estradiol and \u03b2-naphthoflavone on the inflammatory status of release of adipocytokines in 3T3-L1 adipocytes in vitro

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor, recently developed as a drug of choice for initial anti-retroviral (ARV) treatment of HIV-1 infection, whereas estradiol is a major component of hormonal contraceptives. Both drugs have effects on lipid metabolism, impairment of adipocyte differentiation and alteration of adipose tissue distribution and function.This study investigated the effects of different concentrations of either rilpivirine or estradiol either alone or in combination on adipocyte differentiation and adipocytokines status in vitro in the absence and presence of β-naphthoflavone, (BNF),a potent agonist of the aryl hydrocarbon receptor. 3T3-L1 human pre-adipocytes were cultured and differentiated with different concentrations of treatment drugs. After 10 days of differentiation procedure, cells were examined for their morphology and viability. Glycerol,adiponectin, leptin, resistin and interleukin-8 (IL-8) were quantified using commercially available kits. The results show that either rilpivirine or estradiol individually or during their combination can evoke significant increases in glycerol release and a concomitant significant decrease of adiponectin from adipocytes. These effects were dose–dependent. The effects of combined treatments were much larger than individual concentration for each drug. Both drugs had little of no effect on leptin levels, except for a small decrease with 10 µM rilpivirine alone or when combined with estradiol. In addition, both drugs evoked small increases in the release of resistin and interleukin-8 with significant values at higher doses compared to untreated adipocytes.When adipocytes were pretreated with BNF, either rilpivirine or, estradiol or when combined evoked a much larger release in glycerol and a much larger decrease in adiponectin compared to the absence of BNF. In contrast, BNF pretreatment had little of no effect on either leptin, resistin or IL-8 metabolism compared to the results obtained in the presence of either rilpivirine or estradiol alone or in combination.These results show that rilpivirine and estradiol either alone or when combined or pretreated with BNF can evoke marked effects on glycerol and cytokines levels from adipocytes. However, their mechanism (s) in inducing adipogenesis warrants further investigation of different transcription factors at gene expression levels.

Comparison of Characteristics and Survival between Prospective and Retrospective Korea Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome Cohort Studies.

By comparing the data of prospectively and retrospectively enrolled cohorts, we evaluated whether the prospective cohort represented all patients in the retrospective cohort. The prospectively enrolled subjects were older and had lower CD4+ T cell counts, higher viral load. In addition, the initial antiretroviral treatment regimen of the prospective cohort consisted of less integrase strand transfer inhibitor-containing regimens. The 20-year survival rate was 51.8% in the prospective cohort and 84.6% in the retrospective cohort, respectively (P = 0.844). This study suggests the prospective cohort study may not represent all patients.

Clinical Impact of Virological Failure and Resistance Analysis Definitions used in Pivotal Clinical Trials of Initial Antiretroviral Treatment: A Systematic Review

There are no standardized criteria to characterize confirmed protocol-defined virological failure (PDVF) nor the inclusion criteria for the resistance analysis population (RAP) in Phase III randomized clinical trials (RCTs) of initial antiretroviral therapy (ART). We assessed the clinical impact of mismatching between virological non-response (HIV-1 RNA ≥50 copies/mL), confirmed PDVF (48 weeks), and RAP definition in studies with the newest first-line ART. A systematic review of all Phase III RCTs was performed, including preferred once-daily ART (EACS European AIDS guidelines) or recently approved by the US Food and Drug Administration. We identified 16 treatment arms (14 RCTs) with 6175 participants treated with dolutegravir, bictegravir, elvitegravir/cobicistat, raltegravir, darunavir/cobicistat, rilpivirine, or doravirine. Plasma HIV-1 RNA thresholds for PDVF or RAP ranged from 40 to 50, 200, 400, and 500 copies/mL. This led to discrepancies between trials regarding the participants defined as virological non-responders, PDVF, or included in RAP. Overall, 85/296 (29%) patients with PDVF were not genotyped. There was a linear correlation between the threshold of HIV RNA chosen to perform genotyping and rates of participants with PDVF but not genotyped. Only eight treatment arms genotyped all participants with PDVF. Most of the remaining eight arms genotyped roughly < 50% of those with PDVF. In summary, the absence of standardized definitions of VF and criteria for resistance testing in pivotal Phase III RCTs of the first-line ART leads to the possibility of underreporting of resistance mutations when genotypes are only performed at higher viral load cutoffs. Stringent homogeneous criteria should be defined to ensure that all participants with PDVF (e.g., confirmed HIV RNA ≥ 50 copies/mL and the second > 200 copies/mL) undergo genotyping.

Prevalence of antiretroviral resistance in Uruguayan children and adolescents infected with the human immunodeficiency virus in the Reference Center HIV-AIDS. Centro Hospitalario Pereira Rossell, Montevideo, Uruguay

Primary and secondary antiretroviral (ARV) resistance rates of 15 and 40% respectively have been reported in worldwide. Its prevalence in Uruguay is unknown. To know the prevalence of ARV resistance in Uruguayan children under 15 years old infected with HIV that are controlled in the Centro Hospitalario Pereira Rossell between 2008 and 2016. Specific objectives: Quantify primary and secondary mutations, to identify variables associated with resistance; to describe if the result of the resistance test contributed to achieve undetectable viral load (VL). Methodos: Observational descriptive, longitudinal follow-up. Only children under 15 years with resistance test done between January first 2008 and December 31th 2016 were included in the study. Maternal and child variables. Fifty six children were included. 36 children (64%) had resistance tests prior to the initiation of ART and the other 20 children (36%) due to therapeutic failure. Total resistance: 28.6% (16 children); 4 (11.1%) children with primary mutations and 12 (60%) secondary mutations. The test result changed the ARV plan in 15 (26.7%) of the 56 children. The change achieved undetectable CV in 8 children at month 6. The ART change was not associated with AIDS or death. Prevalence studies are useful in making decisions about initial ARV treatment. The prevalence of primary mutations was similar to that published, while secondary prevalence was higher.

Cost–effectiveness of initial antiretroviral treatment administered as single vs. multiple tablet regimens with the same or different components

ObjectiveTo evaluate the efficiency of single-tablet regimens (STR) and multiple-tablet regimens (MTR) with exactly the same or different components. MethodsA study was conducted on HIV-1-infected antiretroviral-naïve patients from 6 Spanish or French centers, who were started on treatment with STR-Atripla®, or the same components separately (MTR-SC), or a different MTR (MTR-Other). Effectiveness was measured as percentage of HIV-RNA <50copies/mL at 48 weeks (ITT). Efficiency was the ratio between costs (direct cost of antiretrovirals plus outpatient visits, hospital admissions, and resistance tests) and effectiveness. ResultsThe study included a total of 2773 patients (759 STR-Atripla®, 483 MTR-SC, and 1531 MTR-Other). Median age was 37 years, 15% were HCV co-infected, 27% had a CD4+ count <200cells/μL, and 30% had viral load ≥100.000copies/mL. The duration of the assigned treatment was longer for STR-Atripla® (P<.0001). Response rates (adjusted for CD4+ count, viral load, and clustered on hospitals) at 48 weeks were 76%, 74%, and 62%, respectively (P<.0001). Virological failure was more common in MTR patients (P=.0025), and interruptions due to intolerance with MTR-Other (P<.0001). Cost per responder at 48 weeks (efficiency) was €12,406 with STR-Atripla®, €11,034 with MTR-SC (0.89 [0.82, 0.99] times lower), and €18,353 (1.48 [1.38, 1.61] times higher) with MTR-Other. ConclusionsSTR-Atripla® and MTR-SC regimens showed similar effectiveness, but virological failure rate was lower with STR-Atripla. MTR-SC, considered less convenient, had a marginally better efficiency, mainly due to lower direct costs. MTR-Other regimens had both a worse effectiveness and efficiency. Similar efficiency analyses adjusting for baseline characteristics should be recommended for new STRs.

Virologic Failure Among People Living With HIV Initiating Dolutegravir-Based Versus Other Recommended Regimens in Real-World Clinical Care Settings.

Guidelines for initial antiretroviral treatment (ART) regimens have evolved, with integrase strand transfer inhibitors (INSTIs) increasingly prominent. Research on virologic failure (VF) with INSTI therapy is predominantly from clinical trials not care settings, especially for recently approved medications including dolutegravir. We compared outcomes among people living with HIV (PLWH) who initiated recommended regimens in clinical care across the United States. We examined 2 groups of PLWH at 8 clinics who initiated ART regimens (August 1, 2013-March 31, 2017): those ART treatment-naive at initiation, and those treatment-experienced. The outcome in this longitudinal cohort study was VF, defined as a viral load of ≥400 copies/mL ≥6 months after ART initiation. We examined the proportion of individuals who remained on, switched, or discontinued the regimen. Associations between regimens and outcomes were examined with adjusted Cox proportional hazards models. Among 5177 PLWH, a lower proportion experienced VF on dolutegravir- versus other INSTI- or darunavir-based regimens for previously treatment-naive (7% vs. 12% vs. 28%) and treatment-experienced PLWH (6% vs. 10% vs. 21%). In adjusted analyses, hazard ratios were similar across regimens for the combined outcome of regimen discontinuation or treatment switch. The hazard ratios for VF comparing dolutegravir- to darunavir-based regimens was 0.30 (95% CI: 0.2 to 0.6) among previously treatment-naive PLWH and was 0.60 (95% CI: 0.4 to 0.8) among treatment-experienced PLWH. The proportion of previously treatment-naive PLWH remaining on recommended ART regimens did not differ by regimen. The likelihood of VF was lower with dolutegravir- than darunavir-based regimens for previously treatment-naive and treatment-experienced PLWH.

Choice of initial antiretroviral drugs and treatment outcomes among HIV-infected patients in sub-Saharan Africa: systematic review and meta-analysis of observational studies

BackgroundThe effectiveness of antiretroviral therapy (ART) depends on the choice of regimens during initiation. Most evidences from developed countries indicated that there is difference between efavirenz (EFV) and nevirapine (NVP). However, the evidences are limited in resource poor countries particularly in Africa. Thus, this systematic review and meta-analysis was carried out to summarize reported long-term treatment outcomes among people on first line therapy in sub-Saharan Africa.MethodsObservational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio to compare risk of treatment failure among HIV/AIDS patients who initiated ART with EFV versus NVP were systematically searched. Searches were conducted using the MEDLINE database within PubMed, Google Scholar, HINARI, and Research Gates between 2007 and 2016. Information was extracted using standardized form. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using random-effect, generic inverse variance method.ResultA total of 6394 articles were identified, of which, 29 were eligible for review and abstraction in sub-Saharan Africa. Seventeen articles were used for the meta-analysis. Of a total of 121,092 independent study participants, 76,719 (63.36%) were females. Of these, 40,480 (33.43%) initiated with NVP containing regimen. Two studies did not report the median CD4 cell counts at initiation. Patients who have low CD4 cell counts initiated with EFV containing regimen. The pooled effect size indicated that treatment failure was reduced by 15%, 0.85 (95%CI: 0.75–0.98), and non-nucleoside reverse transcriptase inhibitor (NNRTI) switch was reduced by 43%, 0.57 (95%CI: 0.37–0.89).ConclusionThe risk of treatment failure and NNRTI switch were lower in patients who initiated with EFV than NVP-containing regimen. The review suggests that initiation of patients with EFV-containing regimen will reduce treatment failure and NNRTI switch.

Ritonavir-Boosted Darunavir Plus Two Nucleoside Reverse Transcriptase Inhibitors versus Other Regimens for Initial Antiretroviral Therapy for People with HIV Infection: A Systematic Review.

Background Darunavir is a second-generation protease-inhibitor used with ritonavir (DRV/r) and two nucleoside reverse-transcriptase inhibitors as an option in first-line antiretroviral treatment (ART). Methods We systematically reviewed randomized controlled trials (RCTs) of DRV/r versus other regimens in patients initiating ART. We searched five bibliographic databases and other key resources. We had no language limitations. We assessed bias risk with the Cochrane tool and used GRADE to assess evidence quality. We report findings in terms of risk ratio (RR) with 95% confidence intervals (CI). Findings Three RCTs met inclusion criteria. In plasma viral load suppression, DRV/r outperformed ritonavir-boosted lopinavir at 48 weeks (RR 1.13, 95% CI 1.03–1.25), 96 weeks (RR 1.11, 95% CI 1.02–1.21), and 192 weeks (RR 1.20, 95% CI 1.07–1.35). DRV/r was similar to dolutegravir at 48 weeks (RR 0.96, 95% CI 0.87–1.06) but less effective at 96 weeks (RR 0.84, 95% CI 0.75–0.93). At 96 weeks, DRV/r underperformed raltegravir (RR 0.94, 95% CI 0.88–0.99) but was similar to ritonavir-boosted atazanavir (RR 1.02, 95% CI 0.96–1.09). Overall bias risk was moderate. Evidence quality was also moderate. Interpretation Initial ART regimens using DRV/r should be considered in future World Health Organization guidelines.

Pediatric HIV Infection in Togo: Situation of Child Care in the Central Region from 2008 to 2015

This piece of work covers thirteen (13) AIDS assistance programs sites over the period 1st Jan 2008 to 31st Dec 2015. The study is retrospective, descriptive and cross-sectional based on 292 clinical cases of HIV infected children aged between 0 and 14 years old. A regional committee was charged to validate antiretroviral treatment (ART) prescriptions on a weekly basis. We have also used data from the regional committee register. HIV infected children represent 5.1% of casework on ART. The average starting age for ART was 4.5 years (1-180 months) with a sex ratio (male/female) of 0.9. The clinical classifications according to WHO guidelines were: Stage III (52.3%) and Stage IV (20.3%). The most frequent opportunistic infections were: wasting (40.12%), digestive candida infection (29.0%), acute respiratory infections (22.8%) and skin diseases (17.9%). The HIV type 1 was detected on all of the children (100%). The average rate of CD4 at the beginning of the ART was 552.98 cells/mm3, leading to a severe immuno-suppression in many cases (44.8%). The initial ART was essentially Nevirapine+Lamivudine+Stavudine. HIV infections diagnosis are usually late in the Central Region of Togo and will therefore be improved by the UNAIDS 90-90-90 strategic plan by 2020, through various initiatives. These are: the Prevention of Mother to Child HIV Transmission (PMTCT), the Early Infection Diagnosis (EID) based on Polymerase Chain Reaction (PCR) and the Provider Initiated Testing and Counseling (PITC).

Pediatric HIV Infection in Togo: Situation of Child Care in the Central Region from 2008 to 2015

This piece of work covers thirteen (13) AIDS assistance programs sites over the period 1st January 2008 to 31st December 2015. The study is retrospective, descriptive, and cross-sectional based on 292 clinical cases of HIV infected children aged between 0 and 14 years old. A regional committee was charged to validate antiretroviral treatment (ART) prescriptions on a weekly basis. We have also used data from the regional committee register. HIV infected children represent 5.1% of casework on ART. The average starting age for ART was 4.5 years (1 - 180 months) with a sex ratio (Male/Female) of 0.9. The clinical classifications according to WHO guidelines were: Stage III (52.3%) and Stage IV (20.3%). The most frequent opportunistic infections were: wasting (40.12%), digestive candida infection (29.0%), acute respiratory infections (22.8%) and skin diseases (17.9%). The HIV type 1 was detected on all of the children (100%). The average rate of CD4 at the beginning of the ART was 552.98 cells/mm3, leading to a severe immuno-suppression in many cases (44.8%). The initial ART was essentially NEVIRAPINE + LAMIVUDINE + STAVUDINE. HIV infections diagnosis are usually late in the Central Region of Togo and will therefore be improved by the UNAIDS 90-90-90 strategic plan by 2020, through various initiatives. These are: the Prevention of Mother to Child HIV Transmission (PMTCT), the Early Infection Diagnosis (EID) based on Polymerase Chain Reaction (PCR) and the Provider Initiated Testing and Counseling (PITC).

Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals.

The advent of highly active antiretroviral therapy (HAART) has reduced the morbidity and mortality due to HIV. The World Health Organisation (WHO) antiretroviral treatment (ART) guidelines focus on three classes of antiretroviral drugs, namely: nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI). Two of the most common medications given in first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy.To determine which NNRTI, EFV or NVP, is more efficacious when given in combination with two NRTIs as part of initial ART for HIV infection in adults and children.We used a comprehensive and exhaustive strategy in an attempt to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings from 1996 to 2009.All randomised controlled trials comparing EFV to NVP in HIV-infected individuals without prior exposure to ART, irrespective of the dosage or NRTI backbone.The primary outcome of interest was virologic response to ART. Other primary outcomes included mortality, clinical progression, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were immunologic response to ART, treatment failure, development of ART drug resistance, and prevention of sexual transmission of HIV.Two authors assessed each reference for inclusion and exclusion criteria established a priori. Data were abstracted independently using a standardised abstraction form. Data were analysed on an intention-to-treat basis and reported as per dosage of NVP.We identified seven randomised controlled trials that met our inclusion criteria.The trials were pooled as per dosage of NVP. None of these trials included children.The seven trials enrolled 1,688 participants and found no critical differences between EFV and NVP, except for different toxicity profiles. EFV is more likely to cause central nervous system side-effects, while NVP is more likely to result in raised transaminases and neutropoenia. There was a higher mortality rate in the NVP 400mg once daily arm.The quality of literature to support these conclusions is moderate to high. Drug resistance was slightly less common with EFV than NVP, but the quality of this literature is low since only one of the seven studies reported on this outcome. No studies reported on sexual transmission of HIV. The length of follow-up time, study settings, and NRTI backbone varied greatly.Both drugs have equivalent efficacies in initial treatment of HIV infection when combined with two NRTIs, but different side effects.

Cost–effectiveness of initial antiretroviral treatment administered as single vs. multiple tablet regimens with the same or different components

ObjectiveTo evaluate the efficiency of single-tablet regimens (STR) and multiple-tablet regimens (MTR) with exactly the same or different components. MethodsA study was conducted on HIV-1-infected antiretroviral-naïve patients from 6 Spanish or French centers, who were started on treatment with STR-Atripla®, or the same components separately (MTR-SC), or a different MTR (MTR-Other). Effectiveness was measured as percentage of HIV-RNA <50copies/mL at 48 weeks (ITT). Efficiency was the ratio between costs (direct cost of antiretrovirals plus outpatient visits, hospital admissions, and resistance tests) and effectiveness. ResultsThe study included a total of 2773 patients (759 STR-Atripla®, 483 MTR-SC, and 1531 MTR-Other). Median age was 37 years, 15% were HCV co-infected, 27% had a CD4+ count <200cells/μL, and 30% had viral load ≥100.000copies/mL. The duration of the assigned treatment was longer for STR-Atripla® (P<.0001). Response rates (adjusted for CD4+ count, viral load, and clustered on hospitals) at 48 weeks were 76%, 74%, and 62%, respectively (P<.0001). Virological failure was more common in MTR patients (P=.0025), and interruptions due to intolerance with MTR-Other (P<.0001). Cost per responder at 48 weeks (efficiency) was €12,406 with STR-Atripla®, €11,034 with MTR-SC (0.89 [0.82, 0.99] times lower), and €18,353 (1.48 [1.38, 1.61] times higher) with MTR-Other. ConclusionsSTR-Atripla® and MTR-SC regimens showed similar effectiveness, but virological failure rate was lower with STR-Atripla. MTR-SC, considered less convenient, had a marginally better efficiency, mainly due to lower direct costs. MTR-Other regimens had both a worse effectiveness and efficiency. Similar efficiency analyses adjusting for baseline characteristics should be recommended for new STRs.