Virological Success Research Articles

Outcomes after a virological failure to first-line second-generation INSTI-based therapy in a real-life setting.

Virological failures of first-line second-generation (SG) INSTI-based regimens are rare, usually characterized by low viremia and absence of drug resistance mutations. To explore the efficacy of rescue regimens introduced after virological failure (VF) to a first-line SG-INSTI therapy. This was a retrospective study on people living with HIV (PWH) failing a first-line SG-INSTI regimen [DTG/3TC, BIC/FTC/TAF, DTG-based three-drug regimen (DTG-3DR)] between 24 March 2016 and 31 December 2021. Follow-up accrued from the second viral load (VL) ≥ 50 copies/mL under SG-INSTI regimen (baseline) until virological success (VS, achievement of at least one VL < 50 copies/mL after baseline) or last visit. Cumulative probabilities of VS were estimated by Kaplan-Meier curves and compared using a log-rank test. Overall, of 521 naïve PWH who started a first-line SG-INSTI regimen, 45 (8.6%) had VF after a median of 14.9 (IQR = 6.9-25.9) months: 33/395 (8.4%) individuals failed a DTG-3DR, 11/102 (10.8%) a BIC/FTC/TAF and 1/24 (4.2%) failed a DTG/3TC.At baseline, 12/45 (27%) PWH changed antiretroviral therapy [median baseline VL 134 (IQR = 81-233) copies/mL], while 33 (73%) maintained their failing regimen [median baseline VL 75 (IQR = 60-145) copies/mL].During a median follow-up of 5.13 (IQR = 3.8-7.1) months, 34 (75.6%) PWH achieved VS: 25/33 (75.8%) maintaining their failing regimen, 9/12 (75%) switched regimen; the estimated 6- and 12-months probabilities of VS were 59% and 84%, respectively.There was no difference in VS curves between PWH who maintained their failing regimen and those who switched therapy. Most individuals remained on their failing regimen, achieving spontaneous virological suppression in most cases. These data help to understand a real-life VF scenario in the context of the current SG-INSTI era.

Effectiveness and safety of dolutegravir plus lamivudine in treating HIV in China, including outcomes of patients coinfected with tuberculosis.

Antiretroviral regimens for human immunodeficiency virus (HIV) infection have continuously evolved; however, antiretrovirals can cause severe adverse reactions. Two-drug regimen therapy can decrease lifetime cumulative drug exposure and long-term toxicities associated with multiple antiretrovirals. The preferred 2-drug regimen constitutes dolutegravir (DTG) and lamivudine (3TC). This study determined the rate of virological suppression and incidence of adverse events at week 48 in treatment-naïve people living with HIV initiated on DTG + 3TC. This was a single-center, retrospective, observational study. Treatment-naïve people aged ≥18 years who received at least 1 DTG + 3TC dose between May 2020 and May 2022 were included. Eighty-nine people living with HIV were enrolled. Twenty-five (28.1%) patients with a DTG + 3TC regimen at baseline were analyzed because of comorbidities, and 48% because of concomitant tuberculosis (TB). Viral suppression at 48 weeks was achieved in 91.67% of patients, and TB was well controlled. At week 48, 84 (94.38%) patients had viral loads < 50 copies/mL, and 21 (91.31%) of the 23 participants with a baseline HIV-1-RNA level ≥ 1 × 105 copies/mL achieved virological success. Fifteen (88.23%) of the 17 participants with a baseline CD4 + cell count of <200 cells/µL achieved virological suppression. The median CD4 + cell count change from baseline was 539.5 cells/µL. No significant changes in triglycerides, low-density lipoprotein cholesterol, weight, or creatinine were observed from baseline to 48 weeks. One patient had severe insomnia at 4 weeks. Our findings support the real-world effectiveness and low metabolic impact of DTG + 3TC. Using DTG + 3TC in patients coinfected with TB and HIV has favorable therapeutic outcomes.

Outcome of Darunavir-Cobicistat-Based Regimens in HIV-Infected People Who Have Experienced Virological Failure.

To evaluate the virological outcome of darunavir-cobicistat (DRVc)-based regimens in adults living with HIV who had experienced virological failure (VF) on any previous drug combination. This was a retrospective cohort study (CSLHIV Cohort) of adults living with HIV who started a DRVc-based regimen with HIV-RNA >50 copies/mL after VF on any previous drug combination. Data on demographics, antiretroviral treatment since HIV diagnosis, and immunological and metabolic parameters from baseline (start of DRVc) to 48 weeks were analyzed in order to assess the cumulative proportion of those who achieved virological success (VS), defined as at least one instance of HIV-RNA <50 copies/mL within 12 months from baseline. Follow-up lasted from the start of the DRVc-based regimen (baseline) to the first instance of HIV-RNA <50 copies/mL, last available visit, or lossto follow-up or death, whichever occurred first. Univariate and multivariate Cox proportional-hazard regression models were used to identify baseline factors associated with VS. A total of 176 individuals were included, and 120 (68.2%) achieved <50 HIV-RNA copies/mL within 12 months since baseline. On multivariate analysis, baseline HDL cholesterol was independently associated with the occurrence of VS (adjusted HR 1.021, 95% CI 1.004-1.038; p=0.014). Among the 120 subjects with VS, 27 (22.5%) had had VF during a median follow-up of 20.8 months since the first undetectable HIV-RNA. Resistance testing after VF was available in two cases, which harboured the HIV variant-bearing protease inhibitor-resistance mutations D30N, I50V, and N88D. During a median follow-up of 38.4 months, 65 of 176 (36.9%) individuals discontinued DRVc for any reason (37 of 120, 30.8%) and achieved VS vs. 28 of 56 (50%) without VS (p=0.019). Time to discontinuation was longer in people with VS (41.5 vs. 23.0 months, p=0.0007). No statistically significant changes were observed in immunological or lipid profiles during follow-up. Most individuals in this study achieved VS within 12 months from the beginning of a DRVc-based regimen; therefore, this treatment represent a viable option for people who have experienced VF on other regimens.

Prevalence of residual replication in HIV-1 patients on Tenofovir, Lamuvidine and Dolutegravir (TLD) treatment followed at Al-Nadjma Multipurpose Center from 2021 to 2023

Objective: The objective of this study is to determine the prevalence of residual replication in HIV-1-infected patients receiving TLD from 2021 to 2023 followed at the Polyvalent Al-Nadjma center. Material and method: This was a retrospective and prospective study with an analytical aim which took place at the Polyvalent Al-Nadjma center from April 2022 to December 2023 in the city of N’Djamena. The study began with the interview of 135 patients, 108 of whom signed informed consent to participate in this study. Patients infected with HIV 1 on ART based on the combination of Tenofovir, Lamivudine and Dolutegravir (TLD) for at least 2 years with a load of 999 copies/mL were included. A total of 108 plasmas were collected and analyzed by the RT-PCR technique. The data from the interviews as well as the RT-PCR results were analyzed with R Studio software. Results: the results of this study revealed a female predominance with 70% (76/108) with a M/F sex ratio of 0.42. The average age of the patients was 40.58 ± 9.58 years. The prevalence of persistent residual replication was 22.22% (n = 24/108), 54.60% (n = 59/108) of patients had virological success, and 19.44% (n = 21/108) of patients had a viral load greater than or equal to 1000 copies/mL and 3.70% (n = 4/108) had an invalid plasma viral load. Conclusion: The aim of this work was to determine the prevalence of residual replication in patients infected with HIV-1 under Tenofovir, Lamuvidine and Dolutegravir (TLD) followed at the Al-Nadjima/APMS multipurpose center in N’Djamena, Chad. The prevalence of residual replication in this study was 22.22%. This study demonstrated that individuals with a persistent viral load below 1000 copies/mL were at increased risk of therapeutic and virological failure due to the lack of consensus and failure to control the phenomenon of residual replication in patients infected with HIV-1 under TLD

Clinical outcomes and risk factors for immune recovery and all-cause mortality in Latin Americans living with HIV with virological success: a retrospective cohort study.

Immune reconstitution following antiretroviral therapy (ART) initiation is crucial to prevent AIDS and non-AIDS-related comorbidities. Patients with suppressed viraemia who fail to restore cellular immunity are exposed to an increased risk of morbidity and mortality during long-term follow-up, although the underlying mechanisms remain poorly understood. We aim to describe clinical outcomes and factors associated with the worse immune recovery and all-cause mortality in people living with HIV (PLWH) from Latin America following ART initiation. Retrospective cohort study using the CCASAnet database: PLWH ≥18 years of age at ART initiation using a three drug-based combination therapy and with medical follow-up for ≥24 months after ART initiation and undetectable viral load were included. Patients were divided into four immune recovery groups based on rounded quartiles of increase in CD4 T-cell count at 2 years of treatment (<150, [150, 250), [250, 350] and >350 cells/mm3 ). Primary outcomes included all-cause mortality, AIDS-defining events and non-communicable diseases that occurred >2 years after ART initiation. Factors associated with an increase in CD4 T-cell count at 2 years of treatment were evaluated using a cumulative probability model with a logit link. In our cohort of 4496 Latin American PLWH, we found that patients with the lowest CD4 increase (<150) had the lowest survival probability at 10 years of follow-up. Lower increase in CD4 count following therapy initiation (and remarkably not a lower baseline CD4 T-cell count) and older age were risk factors for all-cause mortality. We also found that older age, male sex and higher baseline CD4 T-cell count were associated with lower CD4 count increase following therapy initiation. Our study shows that PLWH with lower increases in CD4 count have lower survival probabilities. CD4 increase during follow-up might be a better predictor of mortality in undetectable PLWH than baseline CD4 count. Therefore, it should be included as a routine clinical variable to assess immune recovery and overall survival.

Molecular Evaluation of HIV-1 HAART Efficacy, Comparison of TDF+3TC+EFV and AZT+3TC+NVP Regimens

Context: The UNAIDS goal of ending the HIV epidemic by 2030 will be achieved primarily through the success of the three &amp;ldquo;95s&amp;rdquo; by 2030, and in particular the third &amp;ldquo;95 &amp;raquo;, which consists of achieving an undetectable viral load thanks to effective antiretroviral treatment. Achieving and maintaining viral suppression is the goal of ART and a good knowledge of the effectiveness of triple ARV therapies can help national HIV programs. Thus, the objective of this study was to evaluate and compare the effectiveness of the two ARTs, Tenovofir + Lamivudine +Efavirenz (TDF+3TC+EFV) and Zidovudine+Lamivudine+ Efavirenz (AZT+3TC+NVP) in their abilities to make the plasma viral load of HIV+ patients under treatment undetectable. &#x0D; &#x0D; Material and method: This is a retrospective study of the management of HIV-1 seropositive patients, followed at the Military Hospital of Ouakam (HMO) Molecular Biology laboratory from 2014 to 2021. The main criterion for evaluating the effectiveness of the treatment was the proportions of patients whose Viral load values were undetectable, VL&amp;lt; 50 copies/ml depending on duration of antiretroviral therapy (ART). Plasma viral load tests were carried out on Abbott Real Time HIV-1&amp;reg; (m2000sp/rt) and COBAS&amp;reg;AmpliPrep/COBAS&amp;reg;TaqMan&amp;reg; (Roche) version 2.0. Variables with p&amp;lt;0.05 were considered statistically significant for all comparisons between groups.&#x0D; &#x0D; Results: 3,335 patients met the inclusion criteria, including 2,078 on TDF+3TC+EFV, 445 on AZT+3TC+NVP and 812 were excluded due to death, transfer or loss to follow-up. At 6 months of ART, VL was undetectable in 7.3% of patients on TDF+3TC+EFV and 6.7% of patients on AZT+3TC+NVP (P=0.67). 78.2% versus 73.4% of patients had an undetectable VL respectively for TDF+3TC+EFV and AZT+3TC+NVP at 12 months of ART (p=0.03). TDF+3TC+EFV had significantly higher virological success rates than AZT+3TC+NVP (85.7% versus 80.2%) and virological failure (VL&amp;gt;1000 copies/ml) was significantly greater in patients taking AZT+3TC+NVP (13% versus 7.2%) after 18 months (P=0.001). Gender and age had a significant relationship in treatment success.&#x0D; &#x0D; Conclusion: TDF+3TC+EFV was superior in terms of virological suppression at the end of the study period. These results support the WHO recommendation to use TDF+3TD+EFV as an alternative first-line regimen.

Prevalence of HIV drug resistance among adolescents receiving ART in Cameroon with low- or high-level viraemia.

To characterize HIV drug resistance (HIVDR) below and above the WHO threshold of 1000 copies/mL, considered for the definition of HIV ART failure in resource-limited settings. From a cohort of 280 adolescents (aged 10-19 years) receiving ART for at least 6 months, genotypic resistance testing (GRT) was attempted for two groups of participants: participants with low-level viraemia [LLV; viral load (VL) 200-999 copies/mL] and those in virological failure (VF; confirmed VL ≥1000 copies/mL) using an in-house method. The Stanford HIValg Program was used to identify relevant HIVDR mutations and predict the efficacy of the newly introduced tenofovir-lamivudine-dolutegravir combination. GRT was successfully performed in 54/58 (93.1%) eligible participants, of which 28/31 (90.3%) were in VF and 26/27 (96.3%) had LLV. A high level of resistance was found both in adolescents with LLV and those in VF, with respectively 84.6% (22/26) and 75.0% (21/28) of participants harbouring at least one HIVDR mutation. NRTIs and NNRTIs were the most affected drug classes in both population groups. In contrast, PIs were not significantly affected and dolutegravir was expected to be active for all participants tested. However, for the newly introduced dolutegravir-based combination, functional monotherapy (dolutegravir only) was potentially possible for 22.7% (5/22) of the participants with LLV. Our findings show that the 1000 copies/mL threshold is not an indicator of virological success and we call for a revision of the current WHO definition of VF in resource-limited countries.

Long-term outcomes of highly experienced people with HIV undergoing salvage therapy with raltegravir.

Raltegravir and other third-line drugs have shown promise in improving outcomes in treatment-experienced patients. However, the efficacy and tolerability of these agents vary. This study assessed real-life virologic success, long-term survival, and adverse events in patients receiving raltegravir or other third-line drugs as salvage regimens. This retrospective cohort study included adults who experienced treatment failure (human immunodeficiency syndrome-1 RNA plasma viral load >1000 copies/mL) and subsequently initiated raltegravir or other third-line drugs (darunavir/ritonavir, maraviroc, or etravirine). Propensity score matching methods were employed to account for differences at the time of switching from failing antiretroviral therapy regimens. The matched subset was analyzed using the Kaplan-Meier method and Generalized Wilcoxon tests to evaluate the probability of achieving virologic suppression (plasma viral load <50 copies/mL). Mortality rates, toxicity, treatment interruption, virologic failure, and loss to follow-up were determined using Poisson regression. One hundred and sixty-eight patients initiating salvage regimens were included, with 123 receiving raltegravir and 45 other third-line drugs. Propensity score matching resulted in a subset of 90 patients, 45 in each group. During the follow-up period, there were no significant differences observed between the groups in terms of virologic suppression (77.8% vs 82.2%, P = .73), mortality rates (4.04 vs 6.18 persons per 100 person-years [p-y]; P = .67), drug toxicity (0.00 vs 2.06 persons per 100 p-y; P = .49), treatment interruption (8.07 vs 0.00 persons per 100 p-y; P = .06), virologic failure (2.02 vs 4.12 persons per 100 p-y; P = .61), and loss of follow-up (6.05 vs 4.12 persons per 100 p-y; P = .70). Our findings indicate comparable survival and virological success rates between raltegravir and other drugs used in salvage regimens. Similar rates of drug toxicity, treatment interruption, virologic failure, and loss of follow-up were also observed. These results suggest that raltegravir may be a viable option for salvage therapy, demonstrating outcomes comparable to other third-line drugs in real life.

Molecular Evaluation of the Efficacy of the TDF+3TC+EFV Therapeutic Regimen in the Treatment of HIV-1 Patients

Background: Antiretroviral therapy (ART) has played an important role in the response to HIV infection and has significantly reduced morbidity and mortality worldwide. It allows control of plasma viral load (CV) to an undetectable level CV&lt;50 copies/ml, an indicator of successful treatment. Assessing the effectiveness of ART makes it possible to make recommendations to limit failures in the treatment of HIV. Thus, the objective of this study is to evaluate the efficacy of the TDF+3TC+EFV therapeutic regimen in the treatment of HIV-1 infection. Materials and methods: This is a retrospective study of the treatment of HIV-1 seropositive patients, at the Molecular Biology Laboratory of HMO in Dakar, Senegal, from 2014 to 2021. The main criterion for evaluating the effectiveness of the treatment was the proportion of patients whose viral load value was undetectable (CV&lt;50 copies/ml) according to the duration of ART. Plasma viral load tests were performed on Abbott Real Time HIV-1® (m2000sp/rt) and COBAS®AmpliPrep/COBAS®TaqMan®(Roche) version 2.0. Variables with p&lt;0.05 were considered statistically significant for all comparisons between groups. Results: Of a cohort of 2,704 HIV+ patients, 2,078 met the inclusion criteria and 626 were excluded due to death, transfer or loss to follow-up. The median age was 38 years, women represented 71% patients. At 6 months of treatment, viral suppression was achieved in 8.9% of men and 6.5% of women (P=0.04) and it was significantly greater in young patients aged 0 to 25 years, 11.4% of patients. 79% of women and 75.2% of men had an undetectable viral load at 12 months of ART (P=0.01). Significantly the suppression was better in men in the first 6 months of treatment, they had more virological success, while women responded better to treatment for a duration of 12 months (P=0.01). At the end of the 18-month study period, 85.5% of patients had a suppressed viral load, 5.3% had a decrease in viral load levels and 7.2% of patients had ...

HIV-1 genotypic profiling ensures effective response to third-line antiretroviral therapy in Cameroon.

In order to limit the emergence of human immunodeficiency virus (HIV) drug resistance in a context of limited antiretroviral options, we sought to evaluate the efficacy of third-line (3L) regimens considering HIV genotypic resistance profile at initiation of 3L in Cameroon. A cohort-study was conducted from January-September 2020 among patients initiating a 3L antiretroviral therapy regimen at the Yaoundé Central Hospital. HIV-1 protease-reverse transcriptase was sequenced at the Chantal Biya international reference center for research on HIV/AIDS prevention and management and results were interpreted using Stanford HIVdbv8.3. Good virological response (viral load < 390 copies/mL) was assessed after 12 months using OPP-ERA platform. Statistical analyses were performed using Epi Info v7.2.2.6, with P < .05 considered statistically significant. Of the 38 patients initiating 3L with an available genotyping (42% female; median age, 49 [39-57] years), median cluster of differentiation type 4 count and viral load were 173 [34-374] cells/μL and 169,322 [30,382-551,826] copies/mL, respectively. At enrollment, all patients harbored resistance to reverse transcriptase inhibitors and 66% (25/38) to protease-inhibitors, although 63% (24/38) were still susceptible to darunavir/ritonavir. Preferred 3L regimen was dolutegravir + darunavir/r + tenofovir + lamivudine (51%) and median duration on 3L was 21 [17-32] months. Interestingly, 82% (31/38) of the participants achieved good virological response on 3L, regardless of genotypic profile at recruitment, variations in 3L regimens (P = .9) and baseline cluster of differentiation type 4 count (P = .3). Despite the high burden of reverse transcriptase inhibitor - and protease inhibitor boosted by ritonavir drug resistance, genotyping-guided 3L regimens is accompanied by virological success in most patients. This high efficacy, most likely due to use of high genetic barrier antiretrovirals, requires continuous adherence support alongside close monitoring for long-term effectiveness in similar programmatic settings.

Prevalence of Comorbidities and Polypharmacy in a Historically Minoritized Community and Their Impact on Virologic Suppression in Persons with HIV.

Improved life expectancy from advances in antiretroviral therapy (ART) has been followed by a rise in comorbidities and polypharmacy in this aging population. Historically, polypharmacy has been associated with suboptimal virologic outcomes in persons with HIV, although data in the current ART era and among historically marginalized populations in the United States are limited. We measured the prevalence of comorbidities and polypharmacy, evaluating their impact on virologic suppression. This retrospective IRB-approved cross-sectional study reviewed health records of adults with HIV on ART and receiving care (≥2 visits) in 2019 at a single center in a historically minoritized community. Virologic suppression (HIV RNA <200 copies/mL) based on polypharmacy (≥5 non-HIV medications) or multimorbidity (≥2 chronic conditions) was evaluated. Logistic regression analyses were performed to identify factors associated with virologic suppression, with age, race/ethnicity, and CD4 < 200 cells/mm3 as covariates. Of the 963 individuals that met the criteria, 67%, 47%, and 34% had ≥1 comorbidity, multimorbidity, and polypharmacy, respectively. The cohort demographics were: mean of 49 years (range, 18-81), 40% cisgender women, 46% Latinx individuals, 45% Black individuals, 8% White individuals. Virologic suppression rates were 95% among patients with polypharmacy compared with 86% in those with a lower pill burden (p = 0.0001). The odds of virologic success were higher for individuals with polypharmacy [adjusted odds ratio, aOR = 2.3 (95% confidence interval, CI: 1.2-4.4)] and Latinx identity [aOR = 2.4 (95% CI: 1.5-3.8)], but lower if a CD4 count <200 cells/mm3 [aOR = 0.07 (95% CI: 0.04-0.1)]. The comorbidity burden was higher than previously described, which are driving polypharmacy rates. In the current ART era, polypharmacy is not inherently associated with worse virologic outcomes.

Prevalence and Management of Helminthiasis and Virological Outcomes among HIV Co-infected Under-fives: A Case Study of Mwananyamala Hospital, Tanzania

Background: Helminthiasis (HL) is a parasitic infection caused by worms that infect human body. The disease affects different regions of the world, but it is more prevalent in sub-Saharan African countries. A strong association between immunological status and helminthiasis among under-fives living with HIV infection (ULHI) has been reported.&#x0D; Aim: The study aimed to assess the prevalence and management of helminthiasis and virological outcomes among ULHI receiving health care at the Care and Treatment Centre (CTC) located at Mwananyamala Regional Referral Hospital (MRRH) in Dar es Salaam, Tanzania.&#x0D; Methodology: This was a retrospective and descriptive cross-sectional study involving scrutiny of the clinical records of ULHI, who sought medical attention at MRRH. The clinical records were randomly selected and examined, focusing on the prevalence rate of HL, the co-management of HIV and HL infections, the virological outcome based on the HIV viral load, and other relevant data.&#x0D; Results: A total of 499 ULHI were involved; of those, 254 (50.9%) were females and 245 (49.5%) were males. About 49% of the ULHI had HL. The prevalence of HL and the age of ULHI were both associated with the virological outcome (HVL). ULHI with lower HVL had a relatively greater HL prevalence. The most widely utilized antihelmintics were ABZ, MBZ and IVE, in that order. The most frequently prescribed drugs for co-infections were ABZ-ALL and MBZ-TLD combinations, which exhibited lower HVL.&#x0D; Conclusion: Helminthiasis is still prevalent among ULHI, and use of prophylactic antihelminthics was associated with virological success (lower HVL). The prevalence of HL was relatively higher among ULHI with lower HVL.

Intermittent Bictegravir/Emtricitabine/Tenofovir Alafenamide Treatment Maintains High Level of Viral Suppression in Virally Suppressed People Living with HIV.

In this observational study, we aimed to evaluate whether bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) administered 5 or 4 days a week is able to maintain viral suppression in people living with HIV (PLHIV). We enrolled 85 patients who initiated intermittent B/F/TAF between 28 November 2018 and 30 July 2020: median (IQR) age 52 years (46-59), duration of virological suppression 9 years (3-13), CD4 633/mm3 (461-781). Median follow-up was 101 weeks (82-111). The virological success rate (no virological failure [VF]: confirmed plasma viral load [pVL] ≥ 50 copies/mL, or single pVL ≥ 200 copies/mL, or ≥50 copies/mL with ART change) was 100% (95%CI 95.8-100) and the strategy success rate (pVL < 50 copies/mL with no ART regimen change) was 92.9% (95%CI 85.3-97.4) at W48. Two VF occurred at W49 and W70, in 2 patients self-reporting poor compliance. No resistance mutation emerged at time of VF. Eight patients presented strategy discontinuation for adverse events. There was no significant change in the CD4 count, residual viraemia rate, neither body weight during follow-up, but a slight increase in CD4/CD8 ratio (p = 0.02). In conclusion, our findings suggest that B/F/TAF administered 5 or 4 days a week could maintain the control of HIV replication in virologically suppressed PLHIV while reducing cumulative exposition of ART.

Care and Management of Aegean University HIV Cohort: Change Over Time

Objective: The primary aim of the study was to analyze the changes in time in HIV care and management and virologic success rates. The secondary aims were to analyze the epidemiological features, clinical and laboratory findings, and factors affecting survival. Methods: HIV-infected individuals aged ≥ 18 years presenting to our clinic between January 1996 and December 2015 were included. Data were collected retrospectively from medical records, and two decades (1996-2005 and 2006-2015) were analyzed. Results: Overall, 80% were male; the median age (min; max) was 36.43 (17; 77) years. Patients with stage 3 disease were significantly higher in the first decade compared to the second decade (p=0.00). The median (min; max) CD4+ T lymphocyte count at baseline was 160 (3; 650) and 355 (0; 1800) cells/mm3 in the first and second decades, respectively (p=0.00). The treatment initiation rate was 94.2%; virologic suppression rates at six months of treatment and throughout the total follow-up time were 70.1% and 78.1%, respectively. The difference between the two decades in virologic suppression was significant (p=0.004). AIDS-defining disease developed in 12.9% (52.6% in the first and 11% in the second decade) (p=0.01). The adverse event rate was 60.8%; hyperlipidemia was the most common (60.2%). The death rate was 6.5% and lymphoma (14.3%) and tuberculosis (10.9%) were the most common causes of death. The estimated survival time was 272 months (95% confidence interval 225-320). The inability to achieve virologic suppression, an AIDS-defining disease, and a baseline CD4+ T lymphocyte count &lt;200 cells/mm3 was inversely correlated with survival time. Conclusion: Significant improvements in HIV care and management were recorded in time in our cohort in line with the improvements in global HIV care. Treatment and viral suppression rates were above the Joint United Nations Programme on HIV/AIDS – UNAIDS 90-90-90 target in the second decade. This may be attributed to the recent developments in antiretroviral treatment and the competence of the HIV team in the Aegean University Medical Faculty Infectious Diseases and Clinical Microbiology Department.

Pharmaco-virological algorithm to target risk of drug resistance among a population of HIV-infected key populations in Togo.

No data about ARV treatment coverage and virological response are available among key populations (female sex workers [FSW] and MSM) in Togo. This study aimed to both describe HIV immuno-virological status and evaluate the pertinence of an original algorithm combining pharmacology (PK) and viral load (VL) to identify subjects at risk of ARV drug resistance. A cross-sectional multicentric study was conducted in 2017 in Togo. Our PK-virological algorithm (PK-VA) defines subjects at risk of resistance when exhibiting both detectable plasma drug concentrations and VL>200 c/mL. Among the 123 FSW and 136 MSM included, 50% and 66% were receiving ARV, with 69% and 80% of them successfully-treated, respectively. Genotypes showed drug-resistance mutation (DRM) in 58% and 63% of non-virologically controlled (VL >200 c/mL) ARV-treated FSW and MSM, respectively. PK-VA would have enabled to save 75% and 72% of genotypic tests, for FSW and MSM, respectively. We reported first data about HIV care cascade among key populations in Togo, highlighting they are tested for HIV but linkage to care remains a concern. Furthermore, 70-80% of ARV-treated participants experienced virological success. In limited resources settings, where genotyping tests are beyond reach, PK-VA might be an easiest solution to sort out patients needing ARV adaptation due to resistance. This article is protected by copyright. All rights reserved.

Evaluation of archived drug resistance mutations in HIV-1 DNA among vertically infected adolescents under antiretroviral treatment in Cameroon: Findings during the COVID-19 pandemic.

With the success of antiretroviral therapy (ART), children born with HIV are more likely to reach adolescence. However, frequent non-adherence to ART in adolescents living with HIV (ALHIV) leads to viral replication. Notably, a viraemic infection might lead to archived drug resistance mutations (ADRMs). Hence, within the context of the COVID-19 pandemic, we aimed to compare the patterns of ADRMs in viraemic and non-viraemic vertically infected ALHIV and to assess their immunity to and diagnosis of SARS-CoV-2. A comparative study was conducted among COVID-19-unvaccinated ALHIV receiving ART in Yaoundé-Cameroon over the period October 2021 to March 2022. Plasma HIV-RNA was measured using Abbott® m2000rt; HIV-1 genotyping was performed on buffy-coat (HIV-1 DNA) and ADRMs were interpreted using HIVdb.v9.0.1. Patterns of HIV-1 ADRMs were compared between viraemic (≥ 1.60 log10 HIV-1 RNA copies/ml) and non-viraemic (< 1.60 log10 copies/ml) individuals. SARS-CoV-2 antibodies were assessed on whole blood using Abbott Panbio COVID-19 immunoglobulin G/M (IgG/IgM) rapid test and COVID-19 polymerase chain reaction test was performed using nasopharyngeal swab samples. Of the 60 ALHIV [aged 17 (16-19)years, 51.6% female], median ART duration was 14 (12-16) years; 31/55 (56.3%) were exposed to nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART (of whom 19/31 transitioned to dolutegravir-based ART in 2020) and 24/55 (43.6%) were on second-line ART. Forty-two out of 60 (70.0%) ALHIV were non-viraemic; 43/60 (71.6%) were successfully sequenced. Overall the ADRM rate was 62.7% (27/43), with 69.2% (9/13) viraemic and 60.0% (18/30) non-viraemic (p=0.56). NNRTI-ADRMs were significantly higher among viraemic ALHIV (69.2% vs. 46.7%, p=0.030). Regarding immunity, those with CD4 nadir < 350 cells/μl had significantly higher rates of ADRMs [adjusted odds ratio (aOR) = 3.20 (1.36-95.53), p=0.03]. In relation to COVID-19 immunity, overall SARS-CoV-2 IgG seropositivity was 28.3% (17/60), whereas 0% (0/60) were seropositive to IgM; in particular, those with CD4 count nadir ≥ 350 cells/μl had higher odds of SARS-CoV-2 IgG seropositivity [OR =7.85 (2.03-30.28), p < 0.01]. No significant association was found between SARS-CoV-2 IgG seropositivity and HIV-RNA (non-viraemic, 33.3%; viraemic, 16.7%; p=0.18). SARS-CoV-2 RNA prevalence was 4.5% (2/44). The two positive participants were with low-levels of viral load(Ct > 30) and seropositive to IgG. In the context of virological success, the majority of ALHIV harbour ADRMs, essentially driven by NNRTI mutations and low CD4 nadir. During the current pandemic, about one-third of ALHIV were previously exposed to SARS-CoV-2. However, some children might have been exposed and uninfected and others might have been infected but showed no serological response at sampling. These findings support the use of NNRTI-sparing regimens and the implementation of COVID-19 barrier measures targeting ALHIV during such a pandemic.

Dolutegravir-Based Regimen Ensures High Virological Success despite Prior Exposure to Efavirenz-Based First-LINE ART in Cameroon: An Evidence of a Successful Transition Model.

To ensure optimal prescribing practices in the dolutegravir-era in Cameroon, we compared first-line virological response (VR) under tenofovir + lamivudine + dolutegravir (TLD) according to prior exposure to tenofovir + lamivudine + efavirenz (TLE). A facility-based survey was conducted among patients initiating antiretroviral therapy (ART) with TLD (I-TLD) versus those transitioning from TLE to TLD (T-TLD). HIV viral load was performed and unsuppressed participants (VL > 1000 copies/mL) had genotyping performed by Sanger sequencing. Of the 12,093 patients followed, 310 (mean-age: 41 ± 11 years; 52.26% female) complied with study criteria (171 I-TLD vs. 139 T-TLD). The median ART-duration was 14 (12−17) months among I-TLDs versus 28 (24.5−31) months among T-TLDs (15 (11−19) on TLE and 14 (9−15) on TLD), and 83.15% (148/178) were at WHO clinical stages I/II. The viral suppression rate (<1000 copies/mL) was 96.45%, with 97.08% among I-TLDs versus 95.68% among T-TLDs (p = 0.55). VR was similar in I-TLD versus T-TLD at <400 copies/mL (94.15% versus 94.42%) and age, gender, residence, ART-duration, and WHO stages were not associated with VR (p > 0.05). Genotyping was successful for 72.7% (8/11), with no major mutations to integrase inhibitors found. VR is optimal under first-line TLD after 14 months, even among TLE-exposed, thus confirming the effectiveness of transitioning from TLE to TLD in similar settings, supported by strong pharmacological potency and genetic barrier of dolutegravir.

Determinants of Antiretroviral Treatment Success and Adherence in People With Human Immunodeficiency Virus Treated for Tuberculosis.

In people with human immunodeficiency virus [HIV] presenting with advanced disease, rates of virologic success may be lower than expected. The Reflate TB2 trial did not show non-inferiority of raltegravir versus efavirenz in people with HIV (PWH) treated for tuberculosis. We aimed to identify factors associated with virologic success and higher adherence in the trial. In this analysis, we included participants enrolled in the Reflate TB2 trial with adherence data available. The primary outcome was virologic success (HIV-1 ribonucleic acid [RNA] <50 copies/mL) at week 48, and the secondary outcome was adherence as assessed by the pill count adherence ratio. We used logistic regression to study determinants of virologic success and optimal adherence in 2 separate analyses. Four hundred forty-four participants were included in the present analysis. Over the 48-week follow-up period, 290 of 444 (65%) participants had a pill count adherence ratio ≥95%. At week 48, 288 of 444 (65%) participants were in virologic success. In the multivariate analysis, female sex (adjusted odds ratio [aOR], 1.77; 95% confidence interval [CI], 1.16-2.72; P = .0084), lower baseline HIV-1 RNA levels (<100 000; aOR, 2.29; 95% CI, 1.33-3.96; P = .0087), and pill count adherence ratio ≥95% (aOR, 2.38; 95% CI, 1.56-3.62; P < .0001) were independently associated with virologic success. Antiretroviral pill burden was the only factor associated with pill count adherence ratio ≥95% (OR, 0.81; 95% CI, .71-.92; P = .0018). In PWH with tuberculosis receiving raltegravir or efavirenz-based regimens, female sex, optimal adherence, and baseline HIV-1 RNA <100 000 copies/mL were associated with virologic success, and the number of antiretroviral tablets taken daily was a strong predictor of adherence.

Systematic screening of gender violence and domestic violence among HIV-positive patients: the VIHOLETA study

ABSTRACT We conducted a multicentre observational study in people living with HIV (PLHIV) on antiretroviral therapy in Alicante (Spain) from 2019 to 2020 aiming to analyse the prevalence of abuse and assess treatment adherence according to this variable. We used the Abuse Assessment Screen tool, the simplified medication adherence questionnaire and the medication possession ratio to assess outcomes.. Of the 161 included PLHIV, 53 (32.9%) had suffered abuse (27 emotional abuse, 6 physical abuse, 3 sexual abuse, 13 emotional and physical abuse, 4 unknown type). Seven (4.3%) had suffered abuse in the last year (5 emotional, 2 physical). Abuse had lasted a median of 48 months (interquartile range 12–81). HIV status was considered as a cause of violence by 9.4% of victims. In the multivariable analysis, only abuse was independently associated with non-adherence [adjusted odds ratio (aOR) 3.92; 95% confidence interval (CI) 1.80–8.84; p = 0.0007]. Abuse (aOR 6.14; 95% CI 1.63–27.70; p = 0.001) and previous incarceration (aOR 15.08 95% CI 2.71–104.71; p = 0.003) were associated with detectable viral load. In conclusion, the prevalence of abuse is high in PLHIV, hampering adherence and virological success. Abuse screening tools should be incorporated into routine HIV care.

Brief Report: Efficacy and Safety of Efavirenz, Raltegravir, and Dolutegravir in HIV-1/TB Coinfection. A Multicenter Retrospective Cohort Study in France.

There are limited data comparing the efficacy and safety of raltegravir and dolutegravir to that of efavirenz in HIV-1/tuberculosis (TB) coinfected patients. We conducted a 10-year retrospective study in 4 centers in France. We included all HIV-1/tuberculosis coinfected patients starting antiretroviral therapy with a rifampicin-based regimen, with a plasma HIV RNA level (VL) > 1000 copies/mL. The primary endpoint was the proportion of patients with virological success that is, with VL <50 copies/mL at W48 using an Intention-To-Treat analysis, using last-observation-carried-forward to impute missing data. We also assessed antiretroviral therapy safety, analyzing treatment discontinuation for adverse events. Between 2010 and 2020, 117 patients were included. Thirty-nine (33.3%) were treated with raltegravir and 2 nucleoside reverse transcriptase inhibitors (NRTIs), 19 (16.2%) with dolutegravir (and 2 NRTIs) and 59 (50.4%) with efavirenz (and 2 NRTIs). At W48, the primary endpoint was achieved in 24 patients (61.5%) in the raltegravir group, in 12 (63.2%) in the dolutegravir group, and in 41 (69.5%) in the efavirenz group using an Intention-To-Treat analysis ( P = 0.68). Emergence of drug resistance in patients with virological failure, defined as a VL >50 copies/mL, was observed in 3 patients with efavirenz and one patient with raltegravir. Rate of treatment discontinuation for drug-related adverse events was 10.3%, 10.6%, 16.9% for raltegravir, dolutegravir and efavirenz respectively ( P = 0.67). In this retrospective cohort study, raltegravir and dolutegravir yielded similar efficacy and safety results to efavirenz for the treatment of HIV-1/TB coinfected patients.