Nucleosides And Darunavir/Dolutegravir In Africa

Inclusion Criteria:

1. Male or female, age 12 years and above

2. Body weight at least 40kg

3. Taking a tenofovir plus lamivudine/emtricitabine plus NNRTI-based regimen continuouslyfor a total period of at least 6 months

4. Good adherence to ART, defined as missing medication on no more than 3 days in the onemonth prior to screening. [Patients who do not have good adherence should be givenadherence counselling and re-assessed after an interval of not less than 4 weeks].

5. HIV treatment failure defined by virological criteria (modified from WHO 2016criteria); Viral load ≥ 1000 copies/ml at screening AND EITHER Viral load ≥ 1000copies/ml on the previous test, taken after at least 6 months on ART, and at no morethan 6 months prior to screening and at no less than 4 weeks prior to screening, withadherence counselling given after the previous test OR Viral load ≥ 1000 copies/ml ona confirmatory test taken no less than 4 weeks after screening with adherencecounselling given after the screening test

6. If a woman of childbearing potential, must be willing to use effective contraception. [Childbearing potential is defined as being not premenarchal; not post-menopausal (> 12 months of spontaneous amenorrhea and ≥45 years of age); and not permanentlysterilised].

7. Willing and able to provide written informed consent

8. Able to attend regular study follow-up visits

Exclusion Criteria:

1. Prior use of protease inhibitor or integrase inhibitor therapy

2. Requirement for concomitant medication with known major interactions with study drugsfor which drug substitutions or dose alterations are not available or acceptable (ifthe patient requires rifamycin-based TB treatment, rifabutin must be available at thesite).

3. Women who are currently pregnant or breastfeeding.

4. Severe hepatic impairment (with ascites and/or encephalopathy)

5. ALT > 5 times upper limit of normal

6. Estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73m2 at screening calculatedusing the CKD-EPI equation

7. Current participation in another clinical trial or research protocol (may be permittedin some circumstances; but must first be discussed with the NADIA Chief Investigator)

8. Life expectancy of less than one month in the opinion of the treating physician