High Levels Of Viral Suppression Research Articles

Bictegravir Use During Pregnancy: A Multi-Center Retrospective Analysis Evaluating HIV Viral Suppression and Perinatal Outcomes.

This study describes the largest cohort to date (n=147) of pregnant patients living with HIV on bictegravir (BIC). BIC in pregnancy was associated with high levels of viral suppression and similar perinatal outcomes to published literature. These findings support consideration for use of BIC in management of HIV during pregnancy.

Validation of population-level HIV-1 incidence estimation by cross-sectional incidence assays in the HPTN 071 (PopART) trial.

IntroductionCross‐sectional incidence testing is used to estimate population‐level HIV incidence and measure the impact of prevention interventions. There are limited data evaluating the accuracy of estimates in settings where antiretroviral therapy coverage and levels of viral suppression are high. Understanding cross‐sectional incidence estimates in these settings is important as viral suppression can lead to false recent test results. We compared the accuracy of multi‐assay algorithms (MAA) for incidence estimation to that observed in the community‐randomized HPTN 071 (PopART) trial, where the majority of participants with HIV infection were virally suppressed.MethodsHIV incidence was assessed during the second year of the study, and included only individuals who were tested for HIV at visits 1 and 2 years after the start of the study (2016–2017). Incidence estimates from three MAAs were compared to the observed incidence between years 1 and 2 (MAA‐C: LAg‐Avidity <2.8 ODn + BioRad Avidity Index <95% + VL >400 copies/ml; LAg+VL MAA: LAg‐Avidity <1.5 ODn + VL >1000 copies/ml; Rapid+VL MAA: Asanté recent rapid result + VL >1000 copies/ml). The mean duration of recent infection (MDRI) used for the three MAAs was 248, 130 and 180 days, respectively.Results and discussionThe study consisted of: 15,845 HIV‐negative individuals; 4406 HIV positive at both visits; and 221 who seroconverted between visits. Viral load (VL) data were available for all HIV‐positive participants at the 2‐year visit. Sixty four (29%) of the seroconverters and 3227 (72%) prevelant positive participants were virally supressed (<400 copies/ml). Observed HIV incidence was 1.34% (95% CI: 1.17–1.53). Estimates of incidence were similar to observed incidence for MAA‐C, 1.26% (95% CI: 1.02–1.51) and the LAg+VL MAA, 1.29 (95% CI: 0.97–1.62). Incidence estimated by the Rapid+VL MAA was significantly lower than observed incidence (0.92%, 95% CI: 0.69–1.15, p<0.01).ConclusionsMAA‐C and the LAg+VL MAA provided accurate point estimates of incidence in this cohort with high levels of viral suppression. The Rapid+VL significantly underestimated incidence, suggesting that the MDRI recommended by the manufacturer is too long or the assay is not accurately detecting enough recent infections.

Viral suppression after transition from nonnucleoside reverse transcriptase inhibitor- to dolutegravir-based antiretroviral therapy: A prospective cohort study in Lesotho (DO-REAL study).

ObjectivesSince 2018, the World Health Organization has recommended dolutegravir (DTG)‐containing antiretroviral therapy (ART) for most people living with HIV. Country programmes across Africa have subsequently transitioned from other, mostly nonnucleoside reverse transcriptase inhibitor (NNRTI)‐based ART to DTG‐based ART. This study aims to assess the virological impact of programmatic transitioning to DTG‐based ART in Lesotho.MethodsThe prospective Dolutegravir in Real‐Life in Lesotho (DO‐REAL) cohort enrols people living with HIV initiating or transitioning to DTG‐based ART in Lesotho. Here, we present data from participants who transitioned from NNRTI‐ to DTG‐based ART between February and December 2020. Blood samples collected at transition and at 16 weeks’ follow‐up (window 8–32 weeks) were used for viral load (VL) and resistance testing.ResultsAmong 1347 participants, follow‐up data was available for 1225. The majority (60%) were female, median age at transition was 47 years [interquartile range (IQR): 38–56], and median (IQR) time since ART initiation was 5.9 (3.5–9.0) years. Among those with complete VL data, the rate of viral suppression to < 100 copies/mL was 1093/1116 (98%) before, 1073/1116 (96%) at, and 1098/1116 (98%) after transition. Even among those with a VL ≥ 100 copies/mL at transition, 42/44 (95%) achieved suppression to < 100 copies/mL at follow‐up. Seven participants had a VL ≥ 1000 copies/mL at follow‐up and did not harbour any integrase mutations associated with resistance to DTG.ConclusionsThe high levels of viral suppression observed are encouraging regarding virological outcomes upon programmatic transitioning from NNRTI‐ to DTG‐based ART.

Outbreak of Human Immunodeficiency Virus Infection Among Heterosexual Persons Who Are Living Homeless and Inject Drugs - Seattle, Washington, 2018.

Although diagnoses of human immunodeficiency virus (HIV) infection among persons who inject drugs in the United States are declining, an HIV outbreak among such persons in rural Indiana demonstrated that population's vulnerability to HIV infection (1). In August 2018, Public Health-Seattle and King County (PHSKC) identified a cluster of cases of HIV infection among persons living homeless, most of whom injected drugs. Investigation identified 14 related cases diagnosed from February to mid-November 2018 among women who inject drugs and men who have sex with women (MSW) who inject drugs and their sex partners. All 14 persons were living homeless in an approximately 3-square-mile area and were part of a cluster of 23 cases diagnosed since 2008. Twenty-seven cases of HIV infection were diagnosed among women and MSW who inject drugs in King County during January 1-November 15, 2018, a 286% increase over the seven cases diagnosed in 2017. PHSKC has alerted medical and social service providers and the public about the outbreak, expanded HIV testing among persons who inject drugs or who are living homeless, and is working to increase the availability of clinical and prevention services in the geographic area of the outbreak. This outbreak highlights the vulnerability of persons who inject drugs, particularly those who also are living homeless, to outbreaks of HIV infection, even in areas with high levels of viral suppression and large syringe services programs (SSPs).

High Levels of Viral Suppression Among East African HIV-Infected Women and Men in Serodiscordant Partnerships Initiating Antiretroviral Therapy with High CD4 Counts and During Pregnancy

People who are asymptomatic and feel healthy, including pregnant women, may be less motivated to initiate ART or achieve high adherence. We assessed whether ART initiation, and viral suppression 6, 12 and 24-months after ART initiation, were lower in HIV-infected members of serodiscordant couples who initiated during pregnancy or with higher CD4 counts. We used data from the Partners Demonstration Project, an open-label study of the delivery of integrated PrEP and ART (at any CD4 count) for HIV prevention among high-risk HIV serodiscordant couples in Kenya and Uganda. Differences in viral suppression (HIV RNA <400 copies/ml) among people initiating ART at different CD4 count levels (≤350, 351-500, and >500 cells/mm3) and during pregnancy were estimated using Poisson regression. Of 865 HIV-infected participants retained after becoming eligible for ART during study follow-up, 95% initiated ART. Viral suppression 24-months after ART initiation was high overall (97%), and comparable among those initiating ART at CD4 counts >500, 351-500 and ≤350 cells/mm3 (96% vs 97% vs 97%; relative risk [RR] 0.98; 95% CI: 0.93-1.03 for CD4 >500 vs <350 and RR 0.99; 95% CI: (0.93-1.06) for CD4 351-500 vs ≤350). Viral suppression was as likely among women initiating ART primarily to prevent perinatal transmission as ART initiation for other reasons (p=0.9 at 6 months and p=0.5 at 12 months). Nearly all HIV-infected partners initiating ART were virally suppressed by 24 months, irrespective of CD4 count or pregnancy status. These findings suggest that people initiating ART at high CD4 counts or due to pregnancy can adhere to ART as well as those starting treatment with symptomatic HIV disease or low CD4 counts.

Strengthening HIV therapy and care in rural Tanzania affects rates of viral suppression.

To assess viral suppression rates, to assess prevalence of acquired HIV drug resistance and to characterize the spectrum of HIV-1 drug resistance mutations (HIV-DRM) in HIV-1-infected patients in a rural Tanzanian HIV cohort. This was a cross-sectional study nested within the Kilombero and Ulanga Antiretroviral Cohort. Virological failure was defined as HIV-1 RNA ≥50 copies/mL. Risk factors associated with virological failure and with the development of HIV-DRM were assessed using logistic regression. This study included 304 participants with a median time on ART of 3.5 years (IQR = 1.7-5.3 years); 91% were on an NNRTI-based regimen and 9% were on a boosted PI-based regimen. Viral suppression was observed in 277/304 patients (91%). Of the remaining 27 patients, 21 were successfully genotyped and 17/21 (81%) harboured ≥1 clinically relevant HIV-DRM. Of these, 13/17 (76.5%) had HIV-1 plasma viral loads of >1000 copies/mL. CD4 cell count <200 cells/mm(3) at the time of recruitment was independently associated with a close to 8-fold increased odds of virological failure [adjusted OR (aOR) = 7.71, 95% CI = 2.86-20.78, P < 0.001] and with a >8-fold increased odds of developing HIV-DRM (aOR = 8.46, 95% CI = 2.48-28.93, P = 0.001). High levels of viral suppression can be achieved in rural sub-Saharan Africa when treatment and care programmes are well managed. In the absence of routine HIV sequencing, the WHO-recommended threshold of 1000 viral RNA copies/mL largely discriminates virological failure secondary to HIV-DRM.

HIV Treatment as Prevention: Natural Experiments Highlight Limits of Antiretroviral Treatment as HIV Prevention

There is growing enthusiasm for increasing coverage of antiretroviral treatment among HIV-infected people for the purposes of preventing ongoing transmission. Treatment as prevention will face a number of barriers when implemented in real world populations, which will likely lead to the effectiveness of this strategy being lower than proposed by optimistic modelling scenarios or ideal clinical trial settings. Some settings, as part of their prevention and treatment strategies, have already attained rates of HIV testing and use of antiretroviral therapy—with high levels of viral suppression—that many countries would aspire to as targets for a treatment-as-prevention strategy. This review examines a number of these “natural experiments”, namely, British Columbia, San Francisco, France, and Australia, to provide commentary on whether treatment as prevention has worked in real world populations. This review suggests that the population-level impact of this strategy is likely to be considerably less than as inferred from ideal conditions.

Second-Line Antiretroviral Therapy in a Workplace and Community-Based Treatment Programme in South Africa: Determinants of Virological Outcome

Background: As antiretroviral treatment (ART) programmes in resource-limited settings mature, more patients are experiencing virological failure. Without resistance testing, deciding who should switch to second-line ART can be difficult. The consequences for second-line outcomes are unclear. In a workplace- and community-based multi-site programme, with 6-monthly virological monitoring, we describe outcomes and predictors of viral suppression on second-line, protease inhibitor-based ART. Methods: We used prospectively collected clinic data from patients commencing first-line ART between 1/1/03 and 31/12/08 to construct a study cohort of patients switched to second-line ART in the presence of a viral load (VL) ≥400 copies/ml. Predictors of VL<400 copies/ml within 15 months of switch were assessed using modified Poisson regression to estimate risk ratios. Results: 205 workplace patients (91.7% male; median age 43 yrs) and 212 community patients (38.7% male; median age 36 yrs) switched regimens. At switch compared to community patients, workplace patients had a longer duration of viraemia, higher VL, lower CD4 count, and higher reported non-adherence on first-line ART. Non-adherence was the reported reason for switching in a higher proportion of workplace patients. Following switch, 48.3% (workplace) and 72.0% (community) achieved VL<400, with non-adherence (17.9% vs. 1.4%) and virological rebound (35.6% vs. 13.2% with available measures) reported more commonly in the workplace programme. In adjusted analysis of the workplace programme, lower switch VL and younger age were associated with VL<400. In the community programme, shorter duration of viraemia, higher CD4 count and transfers into programme on ART were associated with VL<400. Conclusion: High levels of viral suppression on second-line ART can be, but are not always, achieved in multi-site treatment programmes with both individual- and programme-level factors influencing outcomes. Strategies to support both healthcare workers and patients during this switch period need to be evaluated; sub-optimal adherence, particularly in the workplace programme must be addressed.

What Conditions Affect Initial HIV Treatment Success?

Highly active antiretroviral therapy has substantially improved the outlook for persons with HIV, and the combination of clinical trial data and experience has provided guidance for the best use of highly active antiretroviral therapy to balance efficacy, safety, tolerability, and adherence. The nonnucleoside reverse transcriptase inhibitors (NNRTIs) and several of the boosted protease inhibitors (PIs, eg, lopinavir/ritonavir) have shown high levels of viral suppression and CD4 count increases as initial therapy. Preliminary evidence suggests that NNRTI regimens may be more forgiving of certain levels of nonadherence than PIs. The evidence also shows that not all agents or combinations of agents are appropriate for all HIV patients. Patient factors such as lipids and triglycerides, hyperglycemia/diabetes, renal function, weight, gender, probability of and desire for pregnancy, initial CD4 count, race, and mental health status will all need to be considered to select the best therapy for the individual.

Pharmacological and therapeutic properties of ritonavir-boosted protease inhibitor therapy in HIV-infected patients.

Boosted protease inhibitor regimens combine ritonavir with a second, 'boosted' protease inhibitor to enhance patient exposure to the latter agent, thereby preventing or overcoming resistance and allowing less frequent dosing, potentially improving adherence. The advantages offered by ritonavir boosting are primarily attributable to the drug's pharmacokinetic properties. Ritonavir's inhibition of the cytochrome P-450 CYP3A4 enzyme reduces the metabolism of concomitantly administered protease inhibitors and changes their pharmacokinetic parameters, including area under the curve (AUC), maximum concentration (Cmax), minimum concentration (Cmin) and half-life (t1/2). As a result, the bioavailability of the boosted protease inhibitor is increased and improved penetration into HIV reservoirs may be achieved. Boosted protease inhibitor regimens that utilize a low dose of ritonavir (100-200 mg) appear to offer the best balance of efficacy and tolerability. At this dose, ritonavir boosts the bioavailability of the second protease inhibitor without contributing significantly to the side effect profile of the regimen. In clinical trials, regimens boosted with low dose ritonavir have demonstrated high levels of viral suppression in both antiretroviral naïve patients and patients who previously failed antiretroviral therapy, including protease inhibitor therapy. Side effects observed have generally been similar to those associated with the boosted protease inhibitor. Based upon their enhanced drug exposure and demonstrated efficacy, the boosted ritonavir regimens should be among the first options considered for use in clinical practice.

Prospective Randomized Two-Arm Controlled Study To Determine the Efficacy of a Specific Intervention To Improve Long-Term Adherence to Highly Active Antiretroviral Therapy

Background: Nearly perfect compliance seems to be indispensable to obtain the maximum benefit from highly active antiretroviral therapy (HAART). Interventions to ensure a high level of adherence during a relatively long-term period of therapy are necessary. Methods: This is a prospective, randomized, two-arm controlled study including patients starting their first- or second-line HAART who were randomized to receive psychoeducative intervention to implement adherence (experimental group [EG]) or a usual medical follow-up (control group [CG]). We aimed to study the efficacy of a psychoeducative intervention to ensure long-term adherence to HAART, its relation with the virologic efficacy of treatment, and to determine the variables related to long-term adherence. Visits were made at weeks 0, 4, 24, and 48 for data collection. Self-reported adherence was registered at each visit and its veracity was tested by randomized blood analyses performed without previous warning to 40% of patients. Appropriate adherence was defined as the consumption of ≥95% of medication prescribed. Statistical analyses were performed both by the as treated (AT) and the intention to treat missing = failure (ITT) methods. Results: In all, 116 patients were included. At week 48, 94% of patients in the EG versus 69% controls achieved adherence ≥95% (p = .008); 89% of patients in the EG versus 66% controls had HIV-1 RNA levels <400 copies/ml (p = .026). Overall, 85% of patients with adherence ≥95% but only 45% of those with adherence <95% had viral load (VL) <400 copies/ml (p = .008). In multivariate analysis, variables significantly related to adherence were having received a psychoeducative intervention (odds ratio [OR], 6.58; p = .04), poor effort to take medication (OR, 5.38; p = .03), and high self-perceived capacity to follow the regimen (OR, 13.76; p = .04). Self-reported adherence and drug plasma levels coincided in 93% of cases. However, differences in adherence did not reach statistical significance in the ITT analysis although a clear tendency toward benefit was observed in EG. Conclusions: Specific and maintained psychoeducative interventions based on excellence on clinical practice are useful to keep high levels of adherence as well as high levels of viral suppression. There is a clear relation between high adherence levels and virologic success. Assessment of certain specific variables related to adherence may be helpful to monitor patient's compliance in the clinical setting.