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Current drugs for HIV-1: from challenges to potential in HIV/AIDS.

The human immunodeficiency virus (HIV) persists in latently infected CD4+T cells and integrates with the host genome until cell death. Acquired immunodeficiency syndrome (AIDS) is associated with HIV-1. Possibly, treating HIV/AIDS is an essential but challenging clinical goal. This review provides a detailed account of the types and mechanisms of monotherapy and combination therapy against HIV-1 and describes nanoparticle and hydrogel delivery systems. In particular, the recently developed capsid inhibitor (Lenacapavir) and the Ainuovirine/tenofovir disoproxil fumarate/lamivudine combination (

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… Common integrase inhibitors include raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), and bictegravir (BIC) ( Martin et al., 2021 ), all belonging to the INSTI class. … Dolutegravir-rilpivirine coformulation . Curr. Opin. HIV AIDS 13 ( 4 ), 320 – 325 . 10.1097/COH.0000000000000466 29553948 Surve D. H. Jirwankar Y. B. Dighe V. D. Jindal A. B. ( 2020 ). …

Booster-free anti-retroviral therapy for persons living with HIV and multidrug resistance (B-Free): protocol for a multicentre, multistage, randomised, controlled, non-inferiority trial.

INTRODUCTION: Anti-retroviral therapy (ART) simplification strategies are needed for treatment-experienced people with HIV (PWH) and multidrug-resistant viruses. These individuals are commonly treated with boosted ART regimens and are thereby at risk for harmful drug-drug interactions (DDI). In this trial, we aim to assess the efficacy of the combination doravirine, dolutegravir and lamivudine (DOR/DTG/3TC) among people with a history of virological failure who receive boosted ART. METHODS AND ANALYSIS: B-Free is a multistage, randomised, multicentre, open-label, non-inferiority trial, embedd…

Virological failure and treatment interruption among people with unsuppressed viral load on antiretroviral therapy: a cross-sectional analysis of Population-based HIV Impact Assessment surveys in seven sub-Saharan African countries.

BACKGROUND: Viral load suppression among people with HIV on antiretroviral therapy (ART) remains a priority in sub-Saharan Africa. We aimed … age ≥45 years). Men had higher virological failure than women (aPR 1·62 [1·20-2·18]). Compared with dolutegravir, efavirenz-based (aPR 3·64 [2·16-6·13]) and nevirapine-based, atazanavir-based, and lopinavir-based regimens (aPR 3·64 [1·90-6·96]) were associated with virological failure. Suboptimal adherence was associated with virological failure (aPR 2·06 [1·4 …

Reversible HIV-Associated Nephropathy and Concomitant Encephalomyelopathy as the Initial Presentation of Advanced, Untreated HIV.

Human immunodeficiency virus (HIV) can cause severe multiorgan dysfunction when left untreated. Concurrent, severe renal and central nervous … atient was initiated on regular haemodialysis and an intensive antiretroviral regimen consisting of dolutegravir/lamivudine, darunavir, and ritonavir, alongside co-trimoxazole prophylaxis until her CD4 count was over 200 cells/mm3. Over a five-month follow-up period, the patient demonstrated an impressive clinical response. Her plasma viral load decreased to 4 …

Human Immunodeficiency Virus-Associated Vasculitis: A Case Report of Sensorineural Hearing Loss, Bell's Palsy, and Psoriasis Guttata.

Human immunodeficiency virus (HIV) infection can manifest with diverse and nonspecific symptoms, often delaying diagnosis. Neurological and … ic vasculitis, suggesting an inflammatory process related to HIV. Antiretroviral therapy (ART) with dolutegravir/lamivudine was initiated. During early treatment, her psoriasis resolved completely, and there was no recurrence of hearing loss or Bell's palsy. HIV-associated vasculitis is an infrequent but clinically significant manifestation that can affect ves …

Prevalence, associated factors and geospatial patterns of HIV drug resistance in South Africa among the virally unsuppressed adults: updated results from the 2017 national HIV household survey.

BACKGROUND: South Africa bears the highest HIV burden globally, with substantial antiretroviral therapy (ART) scale-up. HIV drug resistance (HIVDR) threatens progress toward UNAIDS 95–95-95 targets. We assessed national HIVDR prevalence and associated factors among virally unsuppressed adults in 2017, before dolutegravir (DTG)-rollout. METHODS: Secondary analysis of the 2017 national HIV household survey, included 1 253 virally unsuppressed (defined as ≥ 1 000 copies/mL) adults (≥ 15 years) with HIVDR results. Survey-weighted analysis generated nationally representative estimates. Weighted mul…

Assessment of drug therapy problems and associated factors among PLWHA and tuberculosis admitted to two referral hospitals in Lusaka, Zambia.

BACKGROUND: Managing the simultaneous treatment of HIV/AIDS and tuberculosis (TB) increases the risk of adverse reactions, drug interactions … mon DTP was sub-therapeutic dosing, accounting for 92 (35.7%) cases. Of these, 74 (80%) were due to Dolutegravir sub-therapeutic dose, while 18 (20%) involved anti-tuberculosis medications. Poor adherence was the second most common DTP, occurring in 51 (19.8%) cases . The physician’s acceptance rate of clinical pharmacists’ interventions was 137 (98.1%). Accor …

Uptake and patterns of PEP use within the context of a dynamic choice HIV prevention model in rural Uganda and Kenya: SEARCH Study.

INTRODUCTION: Post-exposure prophylaxis (PEP) remains underutilized despite being the only prevention option currently available that covers … rvices as per in-country guidelines. In both arms, PEP comprised a 28-day oral Tenofovir/Lamivudine/Dolutegravir course with HIV testing at start and end of the 28-day period. We described patterns of and predictors of self-reported PEP use over the 12 months of follow-up. RESULTS: A total of 1232 participants were enrolled, balanced by arm and country. Of th …

Comparative risk of adverse perinatal outcomes associated with classes of antiretroviral therapy in pregnant women living with HIV: systematic review and meta-analysis.

BACKGROUND: Integrase strand transfer inhibitor (INSTI) dolutegravir (DTG)-based antiretroviral therapy (ART) is recommended by World Health Organisation as preferred first-line regimen in pregnant women living with human immunodeficiency virus (HIV) (WLHIV). Non-nucleoside reverse transfer inhibitor (NNRTI)-based ART and protease inhibitor (PI)-based ART are designated as alternative regimens. The impact of different ART regimens on perinatal outcomes is uncertain. We aimed to assess the comparative risk of adverse perinatal outcomes in WLHIV receiving different classes of ART. MATERIALS AND…

Persistent immune activation and altered gut integrity over time in a longitudinal study of Ugandan youth with perinatally acquired HIV.

INTRODUCTION: Perinatally acquired HIV infection (PHIV) occurs during a critical window of immune development. We investigated changes in sy … both timepoints, oxidized LDL was inversely associated with activated T cells(p<0.01). Switching to dolutegravir at week 96 was significantly associated an elevated level of sCD163 (β=0.4, 95% CI=0.14,0.57, p<0.01), without changes in other markers. CONCLUSION: Ugandan PHIV with viral suppression have some improvement in markers of inflammation over time, how …

Comparison of Virological Efficacy of DTG/ABC/3TG and B/F/TAF Regimens and Discontinuation Patterns in Persons Living with Advanced HIV in the Era of Rapid ART: A Retrospective Multicenter Cohort Study.

INTRODUCTION: International treatment guidelines recommend the rapid initiation of antiretroviral therapy (ART) with bictegravir (B)/emtricitabine (F)/tenofovir alafenamide (TAF) and dolutegravir (DTG)-based regimens for treatment-naïve persons living with HIV (PLWH) irrespective of their disease stage. However, we lack evidence of the virological efficacy, virological failure, and tolerability of coformulated B/F/TAF and DTG/ABC/3TC regimens in persons living with advanced HIV (PLWAH; defined as persons with a CD4+ count of < 200 cells/μL or an AIDS-related opportunistic illness [AOI] at or b…

Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa.

BACKGROUND: Introduction of tenofovir (TDF) plus lamivudine (3TC) and dolutegravir (DTG) in first- and second-line HIV treatment regimens in South Africa warrants characterization of acquired HIV-1 drug resistance (ADR) mutations that could impact DTG-based antiretroviral therapy (ART). In this study, we sought to determine prevalence of ADR mutations and their potential impact on susceptibility to drugs used in combination with DTG among HIV-positive adults (≥ 18 years) accessing routine care at a selected ART facility in KwaZulu-Natal, South Africa. METHODS: We enrolled adult participants i…

Resource and infrastructure challenges on the RESIST-2 Trial: an implementation study of drug resistance genotype-based algorithmic ART switches in HIV-2-infected adults in Senegal.

BACKGROUND: Second-line treatment of HIV-2 in resource-limited settings (RLS) is complicated by a lack of controlled trial data, limited ava … due to the COVID-19 pandemic (which prevented further VL and genotypic testing), planned rollout of dolutegravir-based 1st-line ART, and funding. CONCLUSIONS: The RESIST-2 trial demonstrated that a DBS-based genotypic test can be used to help inform second-line ART decisions as part of a programmatic algorithm in RLS, albeit with significant implementation ch …

Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial.

BACKGROUND: Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few pub … ent-related deaths. INTERPRETATION: Our findings support major guidelines. The integrase inhibitor dolutegravir is currently a preferred regimen for the prevention of perinatal HIV transmission with raltegravir recommended as a preferred or alternative integrase inhibitor for pregnant women living with HIV. FUNDING: Eunice Kennedy Shriver National Institute …

Neural Tube Defects in Pregnancies Among Women With Diagnosed HIV Infection - 15 Jurisdictions, 2013-2017.

In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens (1). The World Health Organization* (WHO) and the U.S. Department of Health and Human Services† (HHS) promptly issued interim guidance limiting the initiation of DTG during early pregnancy and in women of childbearing age with HIV …

Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon.

BACKGROUND: Antiretroviral therapy (ART) has improved the survival of HIV infected persons. However, rapid scale-up of ART and the high HIV- … meroon, has prompted the need to rollout an integrase strand transfer inhibitor regimen (containing Dolutegravir) with a higher genetic barrier to resistance as the preferred first line regimen.

Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239.

UNLABELLED: We previously showed that the simian immunodeficiency virus SIVmac239 is susceptible to human immunodeficiency virus (HIV) integ … clear cells (PBMCs) infected with SIVmac239 viruses in the presence of increasing concentrations of dolutegravir (DTG), elvitegravir (EVG), and raltegravir (RAL). We now show that 22 weeks of selection pressure with DTG yielded a mutation at position R263K in SIV, similar to what has been observed in HIV, and that selections with EVG led to emergence of the E9 …

Correlates of Poor Quality of Life Among Older People Living With HIV: A Cross-Sectional Analysis of the Tanzania HIV and Aging Cohort Study.

INTRODUCTION: Older people living with HIV (PLH) have a high multimorbidity burden that may impair quality of life (QOL). This study assesse … IQR: 53-63] years; 50% females; ART duration: 10-19 years [60.3%]), the majority were on first-line dolutegravir-based ART (83.5%) with undetectable viral load (78.5%). The most common medical comorbidities were dyslipidaemia (80.2%), hypertension (54.5%) and overweight/obese (50.8%). Frailty (13.8%) and pre-frailty (48.3%) were observed. Median QOL score was …

Mortality, loss to follow-up and advanced HIV disease following virologic success in West African HIV-2 patients.

BACKGROUND: People living with HIV-2 are mainly found in West Africa and their identification and treatment have been impaired by diagnostic challenges and availability of effective antiretroviral treatment (ART). With the roll out of first line dolutegravir (DTG)-based regimen, the situation may have improved, emphasizing the need for data on long-term treatment outcomes and advanced HIV disease among ART-experienced people living with HIV-2. METHOD: A prospective cohort was initiated in 2012 in Côte d'Ivoire and Burkina Faso. All adult patients from Côte d'Ivoire with an undetectable viral …

Changes to inflammatory markers during 5 years of viral suppression and during viral blips in people with HIV initiating different integrase inhibitor based regimens.

BACKGROUND: Heightened levels of inflammatory markers are linked to increased morbidity/mortality in people with HIV (PWH) and often remain … gating the efficacy and safety of bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) or dolutegravir, abacavir, and lamivudine (DTG/ABC/3TC) or DTG + F/TAF over a 5-year window (GS-US-380-1489/1490). At week 144, participants were offered the option to switch to open label B/F/TAF for an additional 96 weeks. We measured levels of interleukin-6 (IL- …