HIV-1-infection
Conditions
Keywords
HIV Integrase Inhibitors, Sub-Saharan Africa, Anti-HIV Agents, Medication Adherence, Virologic Failure, Viral Drug Resistance, South Africa, Uganda, HIV-1
Brief summary
This is a prospective observational cohort study enrolling participants in South Africa and Uganda who are prescribed an HIV treatment regimen containing lamivudine, tenofovir, and dolutegravir, which is known as TLD. We hope to better understand how effective TLD will be in sub-Saharan Africa. If treatment failure occurs, we seek to understand the possible reasons, including drug resistance and adherence challenges.
Detailed description
This study is a prospective observational cohort study at three government-supported HIV clinics in rural South Africa and Uganda. We will enroll 1,000 adults living with HIV who are switched from first-line antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) to TLD. We will follow participants for one year with study visits at enrollment, 24 weeks, and 48 weeks. Study procedures include interviews, body measurements, chart review, and collection of blood and urine specimens for retrospective testing, including viral load, drug resistance testing, antiretroviral drug level testing, and tests to evaluate the effects of TLD on renal, liver, metabolic, and other organ function. Aim 1: To determine the contributions of resistance prior to switch to TLD from a NNRTI-based regimen to risk of treatment failure after six and twelve months on TLD. Hypothesis: People living with HIV who experience virologic failure on TLD will have increased odds of NRTI mutations prior to TLD exposure, compared to controls with virologic suppression. Aim 2: Explore pharmacologic measures of adherence to distinguish virologic failure on TLD due to suboptimal adherence versus resistance using 2a) urine tenofovir (TFV) levels and 2b) tenofovir diphosphate (TFV-DP) in dried blood spots (DBS). Hypothesis: Absence of TFV in urine and TFV-DP concentrations in DBS will distinguish ART failure with versus without resistance.
Interventions
OTHERThis is an observational study only.
This is an observational study only.
Sponsors
Massachusetts General Hospital
Africa Health Research Institute
Mbarara University of Science and Technology
National Institute of Allergy and Infectious Diseases (NIAID)
Wellcome Trust
ViiV Healthcare
Harvard Medical School (HMS and HSDM)
University of KwaZulu
Emory University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * HIV-positive and in care at one of the study clinics * Current use of NNRTI-based, first-line ART for a minimum of 6 months * Prescribed change to TLD by clinic staff * Residing within 100 kilometers of the treatment clinic without plans to change permanent residence in the next 48 weeks * Consents to participation
Exclusion criteria
There are no specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Virologic Failure (HIV-1 RNA >= 200 Copies/mL) | 48 weeks | HIV-1 RNA \>= 200 copies/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Virologic Failure (HIV-1 RNA >= 1,000 Copies/mL) | 48 weeks | HIV-1 RNA \>= 1,000 copies/mL |
| Proportion of Participants With HIV Drug Resistance | 24 and 48 weeks | Proportion of participants with International AIDS Society-defined drug resistance mutations to their current regimen |
Countries
South Africa, Uganda
Contacts
PRINCIPAL_INVESTIGATORSuzanne M McCluskey, MD
Massachusetts General Hospital
PRINCIPAL_INVESTIGATORMark J Siedner, MD, MPH
Massachusetts General Hospital, Africa Health Research Institute
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 44 years |
| ART regimen prior to TLD Efavirenz-containing regimen | 783 Participants |
| ART regimen prior to TLD Nevirapine-containing regimen | 214 Participants |
| ART regimen prior to TLD Unknown | 2 Participants |
| Education Level No Schooling | 109 Participants |
| Education Level Primary | 341 Participants |
| Education Level Secondary | 441 Participants |
| Education Level Tertiary | 108 Participants |
| Marital Status Married/domestic partnership | 373 Participants |
| Marital Status Single | 626 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 999 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment South Africa | 499 participants |
| Region of Enrollment Uganda | 500 participants |
| Sex: Female, Male Female | 606 Participants |
| Sex: Female, Male Male | 393 Participants |
| Years on ART | 7.4 years |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 999 |
| other Total, other adverse events | 0 / 999 |
| serious Total, serious adverse events | 12 / 999 |
Outcome results
None listed