Full Virological Suppression Research Articles

Changes in epidemiological and treatment-related characteristics among newly reported HIV/AIDS cases in an urban area in Shanghai, China from 2001 to 2019: A population-based retrospective study.

The HIV/AIDS epidemic has changed significantly over the past 40 years. Changes in AIDS intervention strategies over time and across regions may have influenced epidemiological characteristics and intervention strategies. The aim of the current study was to analyze the changes in multi-year epidemiological characteristics of newly reported HIV/AIDS cases in an urban area (the Fengxian District of Shanghai) from 2001 to 2019 based on the national AIDS comprehensive data information system and Shanghai Statistical Yearbook. In total, the average annual incidence of HIV/AIDS was 1.92 per 100,000 persons. The annual incidence fluctuated and tended to increase from 2001 to 2019 (χ2 = 128.38, p < 0.001). More male patients were reported compared to female patients, accounting for 82.9%. The proportion of patients over 65 years of age increased from 5% in 2009 to 12% in 2019. The majority of cases involved sexual contact (97.7%), early diagnosis (58.8%), full virologic suppression (72.9%), and early antiretroviral therapy (ART) (44.3%). Migrant patients have significantly increased over the years. There were significant differences between local and migrant patients in terms of the age at diagnosis, transmission route, and baseline CD4 count. The disparity in high-risk temporal clusters was also explored to indicate the delay of an epidemic between local patients and migrant patients. HIV remains at a low endemic level. AIDS prevention and control measures have been highly effective, and especially in virologic suppression of ART and early diagnosis. More efforts should be made to enhance early diagnosis and treatment among key vulnerable groups, including the elderly in the local population and young male migrants, and the scale of HIV/AIDS testing should be expanded to the general population to control HIV transmission.

Can simplified antiretroviral drug combination therapies resist resistance?

Can simplified antiretroviral drug combination therapies resist resistance?

Distinct immune profiles of HIV-infected subjects are linked to specific lipid mediator signature.

Introduction:To date, with no prophylactic human immunodeficiency virus (HIV) vaccine available, HIV incidence rates remain undefeated. Despite full virological suppression, HIV+ individuals exhibit a higher rate of cardiovascular disorders and cancers what is attributed to the residual, persistent levels of immune activation.Methods:We have established the Virological and Immunological Monitoring (VIM) platform and forty VIM samples that included treated immunological responders (IRs) or nonresponders (INRs), viremic untreated subjects and uninfected controls, were phenotyped by flow cytometry and plasma was used to quantify proinflammatory eicosanoids and the specialized proresolving mediators by liquid chromatography tandem mass spectrometry.Results:While HIV infection profoundly altered lipid mediator (LM) profile, differences were also seen in patients on viral suppressive therapy. IRs exhibited higher levels of proresolving mediators as compared to INRs and notable differences in plasma LM were also seen in early and late treated individuals.Conclusions:This study demonstrated distortions in proinflammatory/proresolution processes in infected patients including those with controlled viremia.

Extinguish the Fire: Anti-inflammatory Strategies for Over Immune Activation in Chronic HIV-1 Infection

Extinguish the Fire: Anti-inflammatory Strategies for Over Immune Activation in Chronic HIV-1 Infection

Characteristics and viral suppression among people living with HIV from the National Free Antiretroviral Therapy Programme, 2019.

This study aimed to present the clinical characteristics of and viral suppression in the national antiretroviral therapy (ART) cohort in China. A cross-sectional study was conducted among the participants enrolled in China's National Free Antiretroviral Therapy Programme (NFATP) who were on ART at the end of 2019. The data used were from China's NFATP information system. The primary outcome was viral load (VL) suppression. Full virological suppression and low-level viraemia (LLV) were defined as VL<50copies/mL and between 51 and 999copies/mL, respectively. At the end of 2019, 853429 people living with HIV (PLWH) were on ART. The median age was 44years [interquartile range (IQR): 33-54]. The majority of PLWH were 25-44years old (47.2%) and male (73.5%) and reported HIV infection via heterosexual contact (64.5%). The median (IQR) baseline CD4 count was 257 (140-376) cells/μL. Among the 704375 PLWH who were on ART for at least 12months, 82.9% had full virological suppression, 6.5% had VL between 50 and 1000copies/mL (LLV) and 4.3% had VL > 1000copies/mL. Optimal full virological suppression occurred in participants who acquired HIV through homosexual contact (88.4%). Although China can be credited for substantial progress in scaling up ART and viral suppression, challenges remain in some key populations, such as injecting drug users, participants with a history of treatment failure and hepatitis C virus co-infected people. To improve the programme output, additional monitoring and intervention for LLV are necessary.

Better executive function is independently associated with full HIV suppression during combination therapy.

HIV-associated neurocognitive impairment continues to be prevalent and clinically relevant. We examined the relationship between neurocognition and full plasma HIV RNA suppression among study participants over a 15-year period at a large research program. We analyzed the combined prospective studies of the HIV Neurobehavioral Research Program at the University of California at San Diego. Participants were eligible for analysis if on three drug combination antiretroviral therapy with comprehensive neuropsychological testing results. Participants who reported recent nonadherence were excluded. The primary outcome was plasma HIV RNA of 50 copies/ml or less. Generalized estimating equation was used to assess for associations with full virologic suppression taking into account longitudinal visits. There were 1943 participants at baseline, of whom 69.4% had plasma HIV RNA of 50 copies/ml or less. Participants with full suppression were slightly older, less likely to abuse cocaine, and had significantly better executive function. Multivariate analysis with incorporation of longitudinal visits (total = 5555) confirmed current cocaine abuse to be strongly associated with lack of virologic suppression (odds ratio = 0.45, 95% confidence interval = 0.31-0.63). In contrast, increasing age, increasing years of HIV infection, and increasing executive function (odds ratio = 1.18 for T score change of 10, 95% confidence interval = 1.07-1.30) were associated with full virologic suppression. Lack of virologic suppression at baseline was associated with a significant subsequent decline in executive function. In a 15-year research cohort of almost 2000 HIV-infected individuals on combination antiretroviral therapy, better executive function was associated with full virologic suppression, possibly as a result rather than a cause.

Safety and efficacy of elvitegravir, dolutegravir, and raltegravir in a real-world cohort of treatment-naïve and -experienced patients.

The aim of this retrospective cohort study was to compare safety, efficacy and rates and reasons of discontinuation of the 3 currently approved integrase strand transfer inhibitors (INSTIs) elvitegravir (EVG), dolutegravir (DTG), and raltegravir (RAL) in HIV-infected treatment-naïve and -experienced patients in a real-world cohort. One hundred four treatment-naïve patients were prescribed an INSTI-based combined antiretroviral therapy (cART)-regimen (first-line group) and 219 patients were switched to an INSTI-based cART-regimen from another treatment regimen (switch group) at our institution between May 2007 and December 2014. Twelve months after initiation of treatment, 92% of patients in the first-line group (EVG: 96%, n = 22/23; DTG: 92%, n = 34/37; RAL: 90%, n = 28/31) and 88% of patients in the switch group (EVG: 94%, n = 32/34; DTG: 90%, n = 69/77; RAL: 85%, n = 67/79) showed full virological suppression (viral load <50 copies/mL). Side effects of any kind occurred in 12% (n = 12/104) of patients in the first-line group, and 10% (n = 21/219) of patients in the switch group. In the switch group neuropsychiatric side effects (depression, vertigo, and sleep disturbances) occurred more frequently in patients treated with DTG (11%, n = 10) compared to the 2 other INSTI-based cART-regimen (EVG: 2%, n = 1; RAL: 1%, n = 1). Side effects only rarely led to discontinuation of treatment (first-line-group: 2%, n = 2/104; switch-group: 1%, n = 3/219). In this real-world setting, INSTI-based ART-regimens were highly efficacious with no significant differences between any of the 3 INSTIs. Overall, side effects were only rarely observed and generally mild in all subgroups. In light of a slightly higher incidence of vertigo and sleep disturbances in patients switched to DTG, awareness of the potential onset of psychiatric symptoms is warranted during follow-up in those patients.

Cost-effectiveness analysis of infant feeding modalities for virally suppressed mothers in Canada living with HIV.

The aim of the study was to determine whether exclusive breastfeeding or exclusive formula feeding is more cost-effective when a Canadian mother with HIV is adherent to antiretroviral therapy and has full virologic suppression. Current Canadian guidelines recommend that mothers with HIV practice exclusive formula feeding. This contradicts the updated World Health Organization (WHO) guidelines which recommend that mothers with HIV should breastfeed for ≥12 months while receiving support for antiretroviral therapy adherence. Due to the economic and health risks and benefits associated with each modality, there remains expert disagreement on whether the WHO recommendations should be adopted in high-income countries. A microsimulation model was developed to estimate lifetime costs and effectiveness (i.e., infant's quality-adjusted life years) of a hypothetical group of 1,000,000 initially healthy, HIV-negative infants, if the mother with HIV was on antiretroviral therapy with full virologic suppression and either exclusive breastfeeding or exclusive formula feeding. The model was developed from the economic perspective of the Ontario Ministry of Health, taking into account direct costs associated with infant feeding modality as well as related indirect costs born out of the child's lifetime health outcomes. Uncertainties related to model parameters were evaluated using one-way and probabilistic sensitivity analyses. In comparison to exclusive formula feeding, exclusive breastfeeding was the dominant feeding modality (i.e., less costly and more effective) yielding cost-savings of $13,812 per additional quality-adjusted life year gained. Neither one-way nor probabilistic sensitivity analyses altered the conclusions. Despite the risk of HIV transmission, exclusive breastfeeding was more cost-effective than exclusive formula feeding. These findings merit review of current infant feeding guidelines for mothers with HIV living in high-income countries.

Steroid-exacerbated HIV-associated cutaneous Kaposi’s sarcoma immune reconstitution inflammatory syndrome: ‘Where a good intention turns bad’

A 51-year-old man with head and neck skin lesions was diagnosed with Kaposi's sarcoma (KS) as his initial presentation of acquired immunodeficiency syndrome. Following initiation of antiretroviral therapy and subsequent full virologic suppression, his facial lesions worsened, consistent with immune reconstitution inflammatory syndrome (IRIS). He was started on glucocorticoids in an attempt to ameliorate the KS-IRIS but experienced paradoxical worsening of the KS lesions. Steroids were subsequently discontinued and he required chemotherapy for severe and cosmetically disfiguring skin lesions. This article describes the potential for worsening of KS lesions in individuals started on glucocorticoids for KS-IRIS as this has been reported rarely in published literature. The mechanisms underlying this phenomenon remain poorly understood but potential explanations are offered in the case discussion. This article aims to raise clinician awareness on the harms of steroid use in patients with KS-IRIS.

Sustained Virological Response on Second-Line Antiretroviral Therapy following Virological Failure in HIV-Infected Patients in Rural South Africa

ObjectiveThis study aims to describe the virological, immunological and clinical efficacy of protease inhibitor (PI)-based second-line antiretroviral therapy (ART) in rural South Africa.MethodsAn observational cohort study was performed on 210 patients (including 39 children) who initiated PI-based second-line therapy at least 12 months prior to data collection. Biannual clinical, immunological and virological monitoring was performed. Primary endpoints were adequate virological response (plasma HIV-1 RNA<400 copies/ml), full virological suppression (plasma HIV-1 RNA<50 copies/ml) and treatment failure (virological failure (plasma HIV-1 RNA>1000 after initial virological response) or on-going viremia (plasma HIV-1 RNA never<400 copies/ml for more than six months)). Data were analyzed by an on-treatment (OT) and intention-to-treat (ITT) approach. Analyses were primarily performed on the group of patients who switched following first-line virological failure.ResultsMedian duration of follow-up after switch to second-line treatment was 20 months [IQR 11–35]. 191 patients had switched to second-line ART due to first-line virological failure. 139/191 of them (72.8%, ITT) were in care and on treatment at the end of follow-up and 11/191 (5.8%, ITT) had died. After twelve months, an adequate virological response was seen in 92/128 patients (71.9%, OT), of which 78/128 (60.9%, OT) experienced full virological suppression. Virological response remained stable after 24 months. Virological efficacy was similar amongst adult and pediatric patients. As in first-line ART, we observed a lack of correlation between virological failure and WHO-defined immunological failure.ConclusionsGood virological outcomes following first-line failure can be achieved with PI-based, second-line antiretroviral therapy in both adult and pediatric patients in rural South Africa. Retention rates were high and virological outcomes were sustainable during the two-year follow-up period, although persisting low-level viremia occurred in a subset of patients. The observed viro-immunological dissociation emphasizes the need for virological monitoring.

Systematic Review of HIV Transmission between Heterosexual Serodiscordant Couples where the HIV-Positive Partner Is Fully Suppressed on Antiretroviral Therapy

BackgroundThe risk of sexual HIV transmission in serodiscordant couples when the HIV-positive partner has full virologic suppression on combination antiretroviral therapy (cART) is debated. This study aims to systematically review observational studies and randomized controlled trials (RCTs), evaluating rates of sexual HIV transmission between heterosexual serodiscordant couples when the HIV-positive partner has full suppression on cART.Methods and FindingsWe searched major bibliographic databases to November 2012 for relevant observational studies and RCTs without language restrictions. Conference proceedings, key journals and bibliographies were also searched. Studies reporting HIV transmission rates, cART histories and viral loads of the HIV-positive partners were included. Two reviewers extracted methodologic characteristics and outcomes. Of 20,252 citations, 3 studies met all eligibility criteria with confirmed full virologic suppression in the HIV-positive partner. We included 3 additional studies (2 cohort studies, 1 RCT) that did not confirm viral suppression in the HIV-positive partner at transmission in a secondary meta-analysis. Methodologic quality was reasonable. The rate of transmission in the 3 studies confirming virologic suppression was 0 per 100 person-years (95% CI = 0–0.05), with low heterogeneity (I2 = 0%). When we included the 3 studies that did not confirm virologic suppression, the rate of transmission was 0.14 per 100 person-years (95%CI = 0.04–0.31) (I2 = 0%). In a sensitivity analysis including all 6 studies, the rate of transmission was 0 per 100 person-years (95%CI = 0–0.01) after omitting all transmissions with known detectable or unconfirmed viral loads, as full suppression in these cases was unlikely. Limitations included lack of data on same-sex couples, type of sexual intercourse (vaginal vs. anal), direction of HIV transmission, exact viral load at the time of transmission, sexually transmitted infections (STI) rates, and extent of condom use.ConclusionsOur findings suggest minimal risk of sexual HIV transmission for heterosexual serodiscordant couples when the HIV-positive partner has full viral suppression on cART with caveats regarding information on sexual intercourse type, STIs, and condom use. These findings have implications when counseling heterosexual serodiscordant couples on sexual and reproductive health. More research is needed to explore HIV transmission risk between same-sex couples.

Sustained virological response on second‐line antiretroviral therapy following virological failure in HIV‐infected patients in rural South Africa

Purpose of the studyOver the last decade, a massive roll‐out of antiretroviral drugs in resource‐limited settings has taken place. In general, good virological responses on first‐line antiretroviral therapy (ART) are achieved in most HIV‐infected patients residing there. Still, a growing number of patients experience virological failure over time, resulting in an increasing need for second‐line regimens [1]. This study describes the clinical, immunological and virological efficacy of protease inhibitor (PI)‐based second‐line ART in a clinic in rural South Africa.MethodsAn observational cohort study was performed on 210 patients (including 39 children) who initiated PI‐based second‐line ART at least 12 months prior to data collection. Biannual clinical, immunological and virological monitoring was performed. Primary endpoints were adequate virological response (HIV‐RNA&lt;400 copies/ml), full virological suppression (HIV‐RNA&lt;50 copies/ml), virological failure (HIV‐RNA&gt;1000 after initial virological response) and on‐going viremia (HIV‐RNA never&lt;400 copies/ml for more than six months). Data were analyzed by an on‐treatment (OT) and intention‐to‐treat (ITT) approach.ResultsMedian duration of follow‐up after switch to second‐line treatment was 21 months [IQR 14–37]. 150/210 patients (71%, ITT) were in care and on treatment at the end of follow‐up and 16/210 (8%, ITT) had died. After twelve months, an adequate virological response was seen in 106/143 patients (74%, OT), of which 86/143 (60%, OT) experienced full virological suppression and 20/143 (14%, OT) showed persisting low‐level viremia (HIV‐RNA between 50 and 400 copies/ml). Furthermore, virological responses remained stable after 24 months of second‐line ART. Virological efficacy was similar amongst adult and pediatric patients. Median increase in CD4 counts from switch until end of follow‐up was 145 cells/mm3 [IQR 1–397] in adults. As in first‐line ART, we observed a lack of correlation between virological treatment failure and WHO‐defined immunological failure in PI‐based therapy.ConclusionsPromising virological outcomes are achieved with PI‐based, second‐line antiretroviral therapy in adult and pediatric patients in rural South Africa. Results were sustainable during the two‐year follow‐up period with a high retention rate, although persisting low‐level viremia occurred in a subset of patients. The observed viro‐immunological dissociation emphasizes the need for virological monitoring.

British HIV Association guidelines for the management ofHIVinfection in pregnant women 2012

British HIV Association guidelines for the management of<scp>HIV</scp>infection in pregnant women 2012

4.0 Screening and monitoring of HIV‐positive pregnant women

4.0 Screening and monitoring of <scp>HIV</scp>‐positive pregnant women

Preventing HIV transmission through antiretroviral treatment-mediated virologic suppression

This review describes important aspects of the research agenda that have emerged as a result of the recent findings of the HIV transmission study in sero-discordant couples conducted by the National Institute of Allergy and Infectious Disease (NIAID)-supported HIV Prevention Trials Network (HPTN) and referred to as HPTN 052. The HPTN 052 study provided strong evidence that antiretroviral treatment (ART), given to HIV-infected partners with the purpose of achieving and maintaining full virologic suppression, could prevent linked HIV transmission in sero-discordant couples. These findings have implications in all future combination prevention strategies. The HPTN 052 study demonstrated that sustained virus suppression, below detectable levels, can prevent HIV transmission in sero-discordant couples. As a result of this study, we have now identified ART as a key component for all combination prevention strategies. Additionally, this study demonstrates that HIV testing is the single door of entry for individualized HIV treatment and prevention. The challenge now is to create a robust, seamless linkage and retention system so that the vision of HIV treatment as prevention can be realized. Such a system will maximize both the treatment and the prevention benefits of ART. The research agenda outlined here describes the need to extend this finding to areas of implementation science, such as the development of simpler, easier to use point-of-care assays for virus load, and improved, better tolerated, more durable combinations and formulations of antiretroviral drugs.

A cluster of patients with recombinant B/F HIV‐1 infection: Epidemiological, clinical, and virological aspects

Migratory processes have caused changes in human immunodeficiency virus (HIV) epidemiology and non-B subtypes are now playing an increasing role. In a cohort of 553 HIV-infected outpatients tested to identify non-B isolates, the largest group consisted of 13 subjects with a recombinant B/F form (prevalence 2.4%). Sequencing and phylogenetic analyses described a B/F recombinant clade with anomalous breakpoints that did not allow it to be classified as CRF12_BF. Viral load was not quantified efficiently because of a mismatch in the primers and probes used by commercial assays. An assessment of the clinical management, and epidemiological, immunological, and virological characteristics of these patients, who were receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-based regimens, showed that the immunological and virological mismatch delayed the start of treatment by a mean of 6.8 months. Therapy was started in nine patients. Both NNRTI- and PI-based regimens led to full virological suppression after a mean 36 weeks of treatment; the PI-based regimens proved to be more effective in terms of immunological recovery (1,341 vs. 544 CD4+ cells/mm(3) ). The spread of non-B subtypes is increasing throughout the world but their response to treatment is still unclear. PIs and NNRTIs are effective but further tests are needed to allow the more efficient recognition of these viral strains and establish how they should be treated.

Protease inhibitor monotherapy and the CNS: peace of mind?

Boosted protease inhibitor (bPI) monotherapy has demonstrated high efficacy for maintaining viral suppression in the blood. bPI monotherapy has the theoretical advantage of avoiding the long-term toxicity associated with the use of nucleoside reverse transcriptase inhibitors. Concern about the efficacy of bPI monotherapy in preventing HIV replication in the CNS is one reason that has precluded the widespread use of this therapeutic strategy. In several studies, a low CNS penetration-effectiveness (CPE) score has been associated with a higher risk of virological failure in the CNS and with neurocognitive impairment. Since the CPE score is substantially lower for bPI monotherapy than for triple-drug highly active antiretroviral therapy (HAART), it has been postulated that bPI monotherapy might have a higher risk for CNS virological failure and neurocognitive impairment. However, the available evidence, although limited, does no support this notion. Lopinavir and darunavir achieve CSF drug levels that are sufficient to fully suppress HIV replication. In clinical trials, when compared with triple-drug HAART, patients receiving bPI monotherapy with lopinavir and darunavir who maintain full virological suppression in plasma do not appear to be at a higher risk of discordant HIV replication in the CSF or of neuropsychiatric adverse events. It should be noted that several studies have suggested that nucleoside reverse transcriptase inhibitors might have neurotoxic effects and, consequently, bPI monotherapy might be able to avoid the CNS toxicity induced by nucleosides. It is clear that more studies including detailed neurocognitive testing are needed to completely establish the risk/benefit ratio of bPI monotherapy or triple-drug HAART for preserving neurocognitive function in HIV-infected patients.

Etravirine in the Treatment of HIV-1: A Clinical Overview for Healthcare Professionals

Current HIV treatment guidelines emphasize the importance of using an active antiretroviral therapy regimen that produces full virologic suppression and immunologic competence, while at the same time providing patients with a favorable safety profile and limited risk for development of drug resistance. Etravirine (TMC125), a recently approved, non-nucleoside reverse transcriptase inhibitor (NNRTI), has shown durable, superior virologic efficacy over placebo in the Phase III, randomized, double-blind DUET trials in 1,203 treatment-experienced, NNRTI-resistant, HIV-1-infected patients. Statistical significance of responses with etravirine over placebo was maintained through Week 24, 48 and 96, regardless of baseline demographics, baseline disease characteristics or the background regimen used. Etravirine has demonstrated a favorable safety and tolerability profile; the incidence of treatment-emergent adverse events was comparable with placebo in the DUET trials, with the exception of rash. The tolerability profile of etravirine also appears to be favorable in terms of neuropsychiatric and hepatic side effects. The pharmacokinetic profile of twice-daily etravirine minimizes the potential for clinically relevant drug-drug interactions and allows for its use in combination with a wide range of other agents. In addition, etravirine has a high genetic barrier to the development of resistance, further enhancing potential benefit in patients infected with NNRTI-resistant virus. The clinical efficacy and favorable safety profile of etravirine, together with its pharmacokinetic profile and high genetic barrier to resistance, make it a valuable treatment option for a wide range of treatment-experienced HIV-1-infected patients.

A Single-Center Cohort Experience of Raltegravir in Salvage Patients Failing Therapy

A Single-Center Cohort Experience of Raltegravir in Salvage Patients Failing Therapy

Successful virological outcome in an HIV-infected individual with a three-class resistant variant and an insertion in the protease genome with a Tipranavir based regimen

Multi-class HIV-1 resistant variants are not rare nowadays. Genotypic and phenotypic resistance testing (including virtual phenotype) constitutes an important tool for optimizing antiretroviral treatment. To report a case of discrepancy between resistance interpretation and virological outcome. A case of a multi-drug experienced patient is presented. Genotypic and/or virtual phenotypic testing analysis was used. The patient after 10 years of antiretroviral therapy with 11 different regimens unable to produce full virological suppression and with a rapidly declining CD4 count, achieved a successful virological outcome with a scheme containing Tipranavir boosted with low dose of ritonavir. Of note, the patient was screened for Tipranavir 1182.48 study and was found ineligible after genotypic analysis. Virologic suppression was achieved despite the fact that neither an active agent was included in the backbone regimen nor the resistance profile could ensure the effectiveness of Tipranavir.