Oligonucleotide Ligation Assay (OLA) Resistance Study
Maneno muhimu
Kikemikali
Maelezo
Durable suppression of HIV replication is critical to (1) improving the health of infected individuals, (2) to reducing HIV transmission to sexual partners and from mothers to their infants, and (3) to maintaining the effectiveness of the current 1st-line non-nucleoside reverse transcriptase inhibitors (NNRTI)- based ART. Across multiple trials, individuals with NNRTI-resistance, even at low-concentrations, have substantially greater virologic failure when treated with NVP- vs PI-ART. A cost-effective strategy is needed to detect and manage ARV-resistant HIV infections. A simple low-cost innovative assay the investigators developed and successfully transferred to Asian and African countries (oligonucleotide ligation assay (OLA)) can detect NNRTI+lamivudine (3TC) resistant HIV using reagents that costs <$7.00/person. Furthermore, detection of NNRTI-resistance by OLA is highly (P<0.001) associated with virologic failure of nevirapine (NVP)-ART in two retrospective studies; one of Thai women who had been previously randomized to single-dose NVP and the second of ARV-naïve Kenyan adults.
The investigators hypothesize that implementation of OLA into routine care will allow Kenyan clinicians to appropriately target protease inhibitor (PI)-based ART and improve rates of durable suppression of viral replication, and thus improve CD4 cell gains and individuals' health, reduce the transmission of ARV-resistant HIV within the community, and maintain the utility of NNRTI-ART. In addition, the investigators hypothesize that programmatically OLA-guided ART will be more cost-efficient compared to the current strategy of empiric use of NNRTI-ART as initial treatment.
Tarehe
| Imethibitishwa Mwisho: | 10/31/2017 |
| Iliyowasilishwa Kwanza: | 07/08/2013 |
| Uandikishaji uliokadiriwa Uliwasilishwa: | 07/10/2013 |
| Iliyotumwa Kwanza: | 07/11/2013 |
| Sasisho la Mwisho Liliwasilishwa: | 11/02/2017 |
| Sasisho la Mwisho Lilichapishwa: | 11/05/2017 |
| Tarehe halisi ya kuanza kwa masomo: | 04/30/2013 |
| Tarehe ya Kukamilisha Msingi iliyokadiriwa: | 11/30/2016 |
| Tarehe ya Kukamilisha Utafiti: | 01/31/2017 |
Hali au ugonjwa
Uingiliaji / matibabu
Other: Pre-ART Oligonucleotide Assay (OLA)
Awamu
Vikundi vya Arm
| Mkono | Uingiliaji / matibabu |
|---|---|
| Experimental: Pre-ART Oligonucleotide Assay (OLA) Pre-ART OLA will be tested for resistance at 5 pol codons conferring high-level resistance to NNRTI and 3TC (K103N, V106M, Y181C, G190A and M184V) | Other: Pre-ART Oligonucleotide Assay (OLA) Block randomization (1:1) to pre-ART OLA testing or OLA testing after 12mo on ART |
| No Intervention: No OLA (Standard of Care [SOC]) The participants will receive standard of care as per Kenya guidelines but will be offered OLA resistance testing after 12 months |
Vigezo vya Kustahiki
| Zama zinazostahiki Kujifunza | 2 Years Kwa 2 Years |
| Jinsia Inastahiki Kujifunza | All |
| Hupokea Wajitolea wa Afya | Ndio |
| Vigezo | Inclusion Criteria: 1. Confirmed HIV infection 2. >2 years of age 3. Qualifying for 1st-line ART based on Kenyan Guidelines 4. Plan to reside in area for >1 year 5. Adult patient or parent of minor agrees to study and provides informed consent Exclusion Criteria: 1. Received ART previously from Hope Center 2. Ongoing ART 3. Plan to start 2nd-line ART |
Matokeo
Hatua za Matokeo ya Msingi
1. The overall difference in rates of virologic failure with OLA-guided ART vs. Standard of care [12 months]
Hatua za Matokeo ya Sekondari
1. The difference in virologic failure among the subgroup of ARV-naïve participants with transmitted drug-resistance (TDR) associated with use of OLA-guided ART vs. SOC [15 months]
2. The difference in virologic failure among the subgroup of participants referred to Hope Center with previous or ongoing ARV use associated with use of OLA-guided ART vs. SOC [15 months]
3. Prevalence of TDR by consensus sequencing and OLA [15 months]
4. Proportion of subgroup with TDR with virologic failure by randomization arm [15 months]
5. Prevalence of TDR increase in the Coptic Clinic [15 months]
6. Estimates of medical resource utilization during the one-year trial period [15 months]
7. An assessment the short-term cost-effectiveness of OLA-guided testing [15 months]
8. An assessment of the potential long-term cost-effectiveness of OLA-guided testing over a patient's lifetime [15 months]
9. Determination of whether low-level ARV resistance (<5%) detected by PYRO but not by OLA is associated with virologic failure [15 months]
Hatua Nyingine za Matokeo
1. Descriptions of technology transfer of OLA to the Hope Center Laboratory, including intra- and inter-assay the reproducibility, and discussion of obstacles and possible solutions [15 months]
2. A comparison of OLA results obtained using DBS in Kenya to retesting of same specimens with input of viral templates measured in Seattle [15 months]
3. A comparison of rates of resistance detected across codons by OLA vs. consensus sequencing in Seattle [15 months]
