Analysis of HIV quasispecies and virological outcome of an HIV D+/R+ kidney–liver transplantation

Abstract Introduction Transplantation among HIV positive patients may be a valuable therapeutic intervention. This study involves an HIV D+/R+ kidney–liver transplantation, where PBMC-associated HIV quasispecies were analyzed in donor and transplant recipients (TR) prior to transplantation and thereafter, together with standard viral monitoring. Methods The donor was a 54 year of age HIV infected woman: kidney and liver recipients were two HIV infected men, aged 49 and 61. HIV quasispecies in PBMC was analyzed by ultra-deep sequencing of V3 env region. During TR follow-up, plasma HIV-1 RNA, HIV-1 DNA in PBMC, analysis of proviral integration sites and drug-resistance genotyping were performed. Other virological and immunological monitoring included CMV and EBV DNA quantification in blood and CD4 T cell counts. Results Donor and TR were all ART-HIV suppressed at transplantation. Thereafter, TR maintained a nearly suppressed HIV-1 viremia, but HIV-1 RNA blips and the increase of proviral integration sites in PBMC attested some residual HIV replication. A transient peak in HIV-1 DNA occurred in the liver recipient. No major changes of drug-resistance genotype were detected after transplantation. CMV and EBV transient reactivations were observed only in the kidney recipient, but did not require specific treatment. CD4 counts remained stable. No intermixed quasispecies between donor and TR was observed at transplantation or thereafter. Despite signs of viral evolution in TR, HIV genetic heterogeneity did not increase over the course of the months of follow up. Conclusions No evidence of HIV superinfection was observed in the donor nor in the recipients. The immunosuppressive treatment administrated to TR did not result in clinical relevant viral reactivations.

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Molecular transmission networks and pre-treatment drug resistance among individuals with acute HIV-1 infection in Baoding, China

PLoS ONE ◽

10.1371/journal.pone.0260670 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0260670

Author(s):

Penghui Shi ◽

Zhixia Chen ◽

Juan Meng ◽

Miaomiao Su ◽

Xuegang Yang ◽

...

Keyword(s):

Drug Resistance ◽

Dynamic Networks ◽

Cross Sectional Study ◽

Gene Sequences ◽

Cross Sectional ◽

Transmission Networks ◽

Cell Counts ◽

Acute Hiv ◽

Pre Treatment ◽

Hiv 1

Background Human immunodeficiency virus type 1 (HIV-1) genetic diversity and pre-treatment drug resistance (PDR) are major barriers to successful antiretroviral therapy (ART). In China, sexual intercourse is the most frequent route of HIV-1 transmission. However, few studies have analyzed PDR and transmission networks in detail among individuals in China with acute HIV-1 infection and their sexual contacts. Methods A cross-sectional study was conducted in Baoding City, Hebei Province, China from 2019–2020. CD4 T cell counts and viral loads were assessed and a HIV-1 genotypic PDR assay was developed in-house. Transmission networks were visualized using Cytoscape with a threshold genetic distance of 0.015 among HIV-1 subtypes. Results From 139 newly diagnosed and drug-naïve individuals with HIV-1, 132 pol gene sequences were obtained and revealed eight HIV-1 subtypes. Circulating recombinant form (CRF)01_AE was the most frequent subtype (53.0%, 70/132) followed by CRF07_BC (26.5%, 35/132), B (13.6%, 18/132), unique recombinant forms (2.3%, 3/132), CRF55_01B (1.5%, 2/132), CRF103_01B (1.5%, 2/132), CRF65_cpx (0.8%, 1/132), and C (0.8%, 1/132). A total of 47 pol gene sequences were used to generate 10 molecular transmission networks. The overall prevalence of PDR was 7.6% and that of PDR to non-nucleotide reverse transcriptase inhibitors was 6.1%. Of three transmission networks for PDR, two were closely associated with Beijing and Tianjin, while another was restricted to sequences determined in this study. Conclusions These results demonstrate that during acute HIV-1 infection, PDR is transmitted in dynamic networks. This suggests that early detection, diagnosis, surveillance, and treatment are critical to effectively control HIV-1 spread.

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Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria

AIDS Research and Therapy ◽

10.1186/s12981-020-00317-9 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Nicaise Ndembi ◽

Fati Murtala-Ibrahim ◽

Monday Tola ◽

Jibreel Jumare ◽

Ahmad Aliyu ◽

...

Keyword(s):

Drug Resistance ◽

Virologic Failure ◽

Resistance Mutations ◽

First Line ◽

Drug Resistance Mutations ◽

Entry Points ◽

The Mean ◽

Living With Hiv ◽

Hiv 1

Abstract Background A substantial number of persons living with HIV (PLWH) in Nigeria do not experience durable viral suppression on first-line antiretroviral therapy (ART). Understanding risk factors for first-line treatment failure informs patient monitoring practices and distribution of limited resources for second-line regimens. We determined predictors of immunologic and virologic failures in a large ART delivery program in Abuja, Nigeria. Methods A retrospective cohort study was conducted at the University of Abuja Teaching Hospital, a tertiary health care facility, using data from February 2005 to December 2014 in Abuja, Nigeria. All PLWH aged ≥ 15 years who initiated ART with at least 6-month follow-up and one CD4 measurement were included. Immunologic failure was defined as a CD4 decrease to or below pre-ART level or persistent CD4 < 100 cells per mm3 after 6 months on ART. Virologic failure (VF) was defined as two consecutive HIV-1 RNA levels > 1000 copies/mL after at least 6 months of ART and enhanced adherence counselling. HIV drug resistance (Sanger sequences) was analyzed using the Stanford HIV database algorithm and scored for resistance to common nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Univariate and multivariate log binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results Of 12,452 patients followed, a total of 5928 initiated ART with at least 6 months of follow-up and one CD4 measurement. The entry point for 3924 (66.2%) was through the program’s own voluntary counseling and testing (VCT) center, while 1310 (22.1%) were referred from an outside clinic/program, 332 (5.6%) in-patients, and 373 (6.3%) through other entry points including prevention of mother to child transmission (PMTCT) and transferred from other programs. The mean CD4 at enrollment in care was 268 ± 23.7 cells per mm3, and the mean HIV-1 RNA was 3.3 ± 1.3.log10 copies/mL. A total of 3468 (80.5%) received nevirapine (NVP) and 2260 (19.5%) received efavirenz (EFV)—based regimens. A total of 2140 (36.1%) received tenofovir (TDF); 2662 (44.9%) zidovudine (AZT); and 1126 (19.0%) stavudine (d4T). Among those receiving TDF, 45.0% also received emtricitabine (FTC). In a multivariate model, immunologic failure was more common among PLWH with female gender as compared to male [RR (95% CI) 1.22 (1.07–1.40)] and less common among those who entered care at the program’s VCT center as compared to other entry points [0.79 (0.64–0.91)], WHO stage 3/4 as compared to 1/2 [0.19 (0.16–0.22)], or CD4 200 + cells per mm3 as compared to lower [0.19 (0.16–0.22)]. Virologic failure was more common among PLWH who entered care at the program’s VCT center as compared to other entry points [RR (95% CI) 1.45 (1.11–1.91) and those with CD4 < 200 cells per mm3 at entry into care as compared to higher [1.71 (1.36–2.16)]. Of 198 patient-derived samples sequenced during virologic failure, 42 (21%) were wild-type; 145 (73%) carried NNRTI drug resistance mutations; 151 (76.3%) M184I/V; 29 (14.6%) had ≥ 3 TAMs, and 37 (18.7%) had K65R, of whom all were on TDF-containing first-line regimens. Conclusions In this cohort of Nigerian PLWH followed for a period of 9 years, immunologic criteria poorly predicted virologic failure. Furthermore, a subset of samples showed that patients failing ART for extended periods of time had HIV-1 strains harboring drug resistance mutations.

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Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring

Clinical Infectious Diseases ◽

10.1093/cid/ciy909 ◽

2018 ◽

Vol 69 (3) ◽

pp. 523-529 ◽

Cited By ~ 2

Author(s):

Sharon A Riddler ◽

Jennifer E Balkus ◽

Urvi M Parikh ◽

John W Mellors ◽

Carolyne Akello ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Disease Progression ◽

Virologic Failure ◽

Vaginal Ring ◽

Phase Iii ◽

Virologic Suppression ◽

Cell Counts ◽

The Impact ◽

Hiv 1

Abstract Background A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). Methods HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network–020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. Results Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P = .40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P = .42). Conclusions The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. Clinical Trials Registration NCT016170096 and NCT00514098.

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Antiretroviral drug resistance mutations in the reverse transcriptase gene of HIV-1 isolates from Northern Indian patients: a follow-up study

Archives of Virology ◽

10.1007/s00705-010-0605-4 ◽

2010 ◽

Vol 155 (4) ◽

pp. 563-569 ◽

Cited By ~ 5

Author(s):

Shubhasree Dutta Choudhury ◽

Alok K. Chaudhury ◽

Rajesh Kalra ◽

Raiees Andrabi ◽

Naveet Wig ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Reverse Transcriptase Gene ◽

Resistance Mutations ◽

Antiretroviral Drug Resistance ◽

Follow Up Study ◽

Drug Resistance Mutations ◽

Antiretroviral Drug ◽

Hiv 1

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Long-Term Outcome of Liver Transplantation in HIV-1-Positive Patients: 15-Year Follow-Up

ISRN Transplantation ◽

10.5402/2013/480582 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8

Author(s):

Shinji Yamamoto ◽

Robert Schwarcz ◽

Ola Weiland ◽

Antti Oksanen ◽

Annika Wernerson ◽

...

Keyword(s):

Liver Transplantation ◽

Highly Active Antiretroviral Therapy ◽

Patient Survival ◽

Biliary Cirrhosis ◽

Term Outcome ◽

Term Survival ◽

Long Term Outcome ◽

Hiv 1

Liver transplantation (LT) for patients with human immunodeficiency virus type-1 (HIV-1) infection has been associated with poor outcome. However, after the introduction of the highly active antiretroviral therapy, short-term patient survival after LT has improved significantly. We examined the long-term outcome of HIV-1-positive patients who underwent LT. Medical records were analysed in nine HIV-1-positive LT patients who underwent LT from August 1998 to May 2012. Eight were known to be HIV-1 positive at the time of listing for LT and had end-stage liver disease (ESLD) due to hepatitis C. One patient had primary biliary cirrhosis, and primary HIV-1 infection was found at the date of LT. Seven of the nine patients remain alive to date. So far, three have survived more than 12 years after LT. The overall patient survival rate for both five and 10 years is 77.8%. Four patients experienced acute rejection and six acquired biopsy-confirmed HCV recurrence. HIV-1 replication was effectively blocked during follow-up in all patients. We conclude that long-term survival of HIV-1-positive patients after LT can be achieved. Our study suggests that LT can offer an effective treatment option in selected HIV-1 infected patients with ESLD.

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Primary HIV-1 resistance: Persistence of transmitted drug resistance mutations

Archives of Biological Sciences ◽

10.2298/abs1204301n ◽

2012 ◽

Vol 64 (4) ◽

pp. 1301-1309 ◽

Cited By ~ 1

Author(s):

Valentina Nikolic ◽

D. Salemovic ◽

Dj. Jevtovic ◽

I. Pesic-Pavlovic ◽

S. Zerjav ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Viral Fitness ◽

Transmitted Drug Resistance ◽

Resistance Mutations ◽

High Level ◽

Hiv 1 ◽

Level Resistance

Transmitted drug resistance (TDR) is one of the consequences of the high variability of HIV-1. The widespread use of antiretroviral therapy for the treatment of HIV-1 infection results in a large circulating pool of resistant virus variants. It is known that TDR mutations can persist for extended periods and may pose an important problem to the overall success of antiretroviral therapy. Factors that determine the duration of continuous persistence of resistance-associated mutations are the number and type of these mutations and their impact on viral fitness. Here we describe the follow-up of a case study of prolonged persistence of resistance-associated mutations, namely RT mutations Q151M, K65KR and Y181C conferring an intermediate-to-high level resistance to multiple NRTIs and NNRTIs that lasted for seven years. The infection was caused by subtype G virus.

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Safety of monitoring antiretroviral therapy response in HIV-1 infection using CD4+ T cell count at long-term intervals

Cadernos de Saúde Pública ◽

10.1590/0102-311x00009618 ◽

2018 ◽

Vol 34 (10) ◽

Author(s):

Ingridt Hildegard Vogler ◽

Daniela Frizon Alfieri ◽

Heloisa Damazio Bruna Gianjacomo ◽

Elaine Regina Delicato de Almeida ◽

Edna Maria Vissoci Reiche

Keyword(s):

Viral Load ◽

T Cell ◽

Antiretroviral Therapy ◽

Sustained Virologic Response ◽

Virologic Response ◽

Cd4 T Cell ◽

Cell Counts ◽

Hiv 1 ◽

Cd4 T Cell Count

Abstract: The latest Brazilian guideline recommended the reduction of routine CD4+ T cell counts for the monitoring of patients with human immunodeficiency virus type 1 (HIV-1) under combination antiretroviral therapy (cART). The aim of this study was to evaluate the safety of monitoring response to cART in HIV-1 infection using routine viral load at shorter intervals and CD4+ T cell count at longer intervals. CD4+ T cell counts and HIV-1 viral load were evaluated in 1,906 HIV-1-infected patients under cART during a three-year follow-up. Patients were stratified as sustained, non-sustained and non-responders. The proportion of patients who showed a CD4+ T > 350cells/µL at study entry among those with sustained, non-sustained and non-responders to cART and who remained with values above this threshold during follow-up was 94.1%, 81.8% and 71.9%, respectively. HIV-1-infected patients who are sustained virologic responders and have initial CD4+ T cell counts > 350cells/µL showed a higher chance of maintaining the counts of these cells above this threshold during follow-up than those presenting CD4+ T ≤ 350cells/µL (OR = 39.9; 95%CI: 26.5-60.2; p < 0.001). This study showed that HIV-1-infected patients who had sustained virologic response and initial CD4+ T > 350cells/µL were more likely to maintain CD4+ T cell counts above this threshold during the next three-year follow-up. This result underscores that the evaluation of CD4+ T cell counts in longer intervals does not impair the safety of monitoring cART response when routine viral load assessment is performed in HIV-1-infected patients with sustained virologic response.

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HIV MDR is still a relevant issue despite its dramatic drop over the years

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz554 ◽

2020 ◽

Vol 75 (5) ◽

pp. 1301-1310 ◽

Cited By ~ 2

Author(s):

D Armenia ◽

D Di Carlo ◽

P Flandre ◽

Y Bouba ◽

V Borghi ◽

...

Keyword(s):

Drug Resistance ◽

Cox Regression ◽

Integrase Inhibitor ◽

Cox Regression Analysis ◽

Virological Success ◽

Susceptibility Score ◽

Inhibitor Resistance ◽

Lower Hazard ◽

Hiv 1

Abstract Objectives To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy. Methods Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999–2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm). Results Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P < 0.001), then remained relatively constant at ∼40% during 2010–18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P < 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P < 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance. Conclusions A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.

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