Long-term effectiveness of first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy in Ghana

Abstract Background The World Health Organization (WHO) HIV Drug Resistance (HIVDR) report 2012 demonstrated that the levels of HIVDR to first-line antiretroviral therapy (ART) are increasing. This finding threatens to reverse a decade of gains in HIV/AIDS epidemic control. The WHO Global Action Plan for HIVDR emphasizes strengthening surveillance of drug resistance through the implementation of national cross-sectional surveys. We conducted such survey to determine the prevalence of HIVDR among ART-naive patients in Zimbabwe and to describe the profile of the surveillance drug resistance mutations (SDRM) encountered in the country. Methods A prospective, nationally representative, cross-sectional survey was conducted in 35 clinical sites selected using two stage probability proportional to size sampling. Patients were enrolled during April–July 2015. Specimens were sent for genotyping to CDC Atlanta. SDRM were interpreted using Stanford HIV Drug Resistance Database classification. Results A total of 361 subjects were surveyed. Most participants were female (60.3%) and the median age was 35.8 years. Thirty-four out of 361subjects presented with ≥1 SDRM (9.4%, 95% confidence interval: 6.8–12.8%) prior to initiation antiretroviral therapy (ART). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most commonly detected mutation (n = 30). Only two patients presented with a nucleoside reverse transcriptase inhibitor mutation and one patient presented with a protease inhibitor mutation. In two patients, ≥3 SDRMs were detected, which may suggest they were not truly ART-naïve. Conclusion This study provides national estimates of HIVDR in a high burden country with broad access to ART and provides valuable inisight on the state of HIVDR in such setting. Zimbabwe has reached moderate levels of HIVDR in ART-naive patients, as specified by the WHO classification. These levels may impact the ability to achieve viral suppression in a significant number of patients initiating standard ART regimens in Zimbabwe, where NNRTI-based regimens are used as the first line. The use of drugs with high resistance barrier, such as dolutegravir, may improve the care of patients in the developing world, where individualized pretreatment genotype is not feasible. Disclosures All authors: No reported disclosures.

Download Full-text

Differentiated Care Pathways for Antiretroviral Therapy Monitoring in Malawi: Expanding Viral Load Testing in Setting of Highly Prevalent Resistance

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx125 ◽

2017 ◽

Vol 4 (3) ◽

Author(s):

Sarah E Rutstein ◽

Kara Compliment ◽

Julie A E Nelson ◽

Deborah Kamwendo ◽

Ronald Mataya ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Therapy Monitoring ◽

Transcriptase Inhibitor ◽

Load Testing ◽

First Line ◽

Inhibitor Resistance ◽

Reverse Transcriptase Inhibitor ◽

Differentiated Care

Abstract We quantified resistance to first-line antiretroviral therapy among previously unmonitored patients in Malawi with viremia (≥1000 copies/mL). Ninety-five percent (n = 57/61) harbored nucleoside/tide reverse transcriptase inhibitor/non-nucleoside reverse transcriptase inhibitor resistance; resistance was more common comparing >2 (97%) versus ≤2 years (87%) on therapy. Immediate switch for persons retained in care may improve monitoring efficiency and maximize clinical outcomes.

Download Full-text

Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations Associated with First-Line Stavudine-Containing Antiretroviral Therapy: Programmatic Implications for Countries Phasing Out Stavudine

The Journal of Infectious Diseases ◽

10.1093/infdis/jit114 ◽

2013 ◽

Vol 207 (suppl_2) ◽

pp. S70-S77 ◽

Cited By ~ 23

Author(s):

Michele W. Tang ◽

Soo-Yon Rhee ◽

Silvia Bertagnolio ◽

Nathan Ford ◽

Susan Holmes ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

Resistance Mutations ◽

First Line ◽

Inhibitor Resistance ◽

Reverse Transcriptase Inhibitor

Download Full-text

Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa

Antiviral Chemistry and Chemotherapy ◽

10.1177/2040206618762985 ◽

2018 ◽

Vol 26 ◽

pp. 204020661876298 ◽

Cited By ~ 5

Author(s):

Kerri J Penrose ◽

Chanson J Brumme ◽

Maritsa Scoulos-Hanson ◽

Kristen Hamanishi ◽

Kelley Gordon ◽

...

Keyword(s):

South Africa ◽

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

Cross Resistance ◽

Subtype C ◽

First Line ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1

Background Rilpivirine (TMC278LA) is a promising drug for pre-exposure prophylaxis of HIV-1 because of its sub-nanomolar potency and long-acting formulation; however, increasing transmission of non-nucleoside reverse transcriptase inhibitor-resistant HIV-1 with potential cross-resistance to rilpivirine could reduce its preventive efficacy. This study investigated rilpivirine cross-resistance among recombinant subtype C HIV-1 derived from 100 individuals failing on first-line non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy in South Africa whose samples were sent for routine HIV-1 drug resistance testing to Lancet Laboratories (Johannesburg, South Africa). Methods Plasma samples were selected from individuals with HIV-1 RNA > 10,000 copies/ml and ≥1 non-nucleoside reverse transcriptase inhibitor-resistance mutation in reverse transcriptase. Recombinant HIV-1LAI-containing bulk-cloned full-length reverse transcriptase sequences from plasma were assayed for susceptibility to nevirapine (NVP), efavirenz (EFV) and rilpivirine in TZM-bl cells. Fold-change (FC) decreases in drug susceptibility were calculated against a mean IC50 from 12 subtype C HIV-1 samples from treatment-naïve individuals in South Africa. Cross-resistance was evaluated based on biological cutoffs established for rilpivirine (2.5-FC) and the effect of mutation combinations on rilpivirine phenotype. Results Of the 100 samples from individuals on failing antiretroviral therapy, 69 had 2.5- to 75-fold decreased susceptibility to rilpivirine and 11 had >75-fold resistance. Rilpivirine resistance was strongly associated with K103N especially in combination with other rilpivirine-associated mutations. Conclusion The frequently observed cross-resistance of HIV-1 suggests that the preventive efficacy of TMC278LA pre-exposure prophylaxis could be compromised by transmission of HIV-1 from individuals with failure of first-line non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy.

Download Full-text

Long-term efficacy of dual nucleoside reverse transcriptase inhibitor antiretroviral therapy in HIV-1 infection

AIDS ◽

10.1097/00002030-200207050-00020 ◽

2002 ◽

Vol 16 (10) ◽

pp. 1432-1433 ◽

Cited By ~ 1

Author(s):

Sandro Vento ◽

Massimiliano Lanzafame ◽

Francesca Cainelli ◽

Federica Faggian ◽

Ercole Concia ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

Term Efficacy ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1

Download Full-text

First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial

The Lancet Infectious Diseases ◽

10.1016/s1473-3099(10)70313-3 ◽

2011 ◽

Vol 11 (4) ◽

pp. 273-283 ◽

Cited By ~ 88

Keyword(s):

Viral Load ◽

Antiretroviral Therapy ◽

Protease Inhibitor ◽

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

Phase 2 ◽

First Line ◽

Open Label ◽

Reverse Transcriptase Inhibitor

Download Full-text

Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients

Scientific Reports ◽

10.1038/s41598-020-80247-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mayumi Imahashi ◽

Hirotaka Ode ◽

Ayumi Kobayashi ◽

Michiko Nemoto ◽

Masakazu Matsuda ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Transcriptase Inhibitor ◽

Strand Transfer ◽

Intestinal Dysbiosis ◽

Α Diversity ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1 ◽

Over Time

AbstractIn HIV-1-infected patients, antiretroviral therapy (ART) is a key factor that may impact commensal microbiota and cause the emergence of side effects. However, it is not fully understood how long-term ART regimens have diverse impacts on the microbial compositions over time. Here, we performed 16S ribosomal RNA gene sequencing of the fecal and salivary microbiomes in patients under different long-term ART. We found that ART, especially conventional nucleotide/nucleoside reverse transcriptase inhibitor (NRTI)-based ART, has remarkable impacts on fecal microbial diversity: decreased α-diversity and increased ß-diversity over time. In contrast, dynamic diversity changes in the salivary microbiome were not observed. Comparative analysis of bacterial genus compositions showed a propensity for Prevotella-enriched and Bacteroides-poor gut microbiotas in patients with ART over time. In addition, we observed a gradual reduction in Bacteroides but drastic increases in Succinivibrio and/or Megasphaera under conventional ART. These results suggest that ART, especially NRTI-based ART, has more suppressive impacts on microbiota composition and diversity in the gut than in the mouth, which potentially causes intestinal dysbiosis in patients. Therefore, NRTI-sparing ART, especially integrase strand transfer inhibitor (INSTI)- and/or non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens, might alleviate the burden of intestinal dysbiosis in HIV-1-infected patients under long-term ART.

Download Full-text