Development of AntiRetroviral Therapy in Africa - a randomised trial of monitoring practice and structured treatment interruptions in the management of antiretroviral therapy in adults with HIV infection in Africa

Conditions

Human Immunodeficiency Virus (HIV), Acquired Immunodeficiency Syndrome (AIDS) Infections and Infestations Human immunodeficiency virus (HIV)

Lisa Ross, A. Sarah Walker, Yu Lou, Allan R. Tenorio, Diana M. Gibb et al. (17 authors)

PLoS ONE2019-11-143 citations

10.1371/journal.pone.0225199

The virological durability of first-line ART among HIV-positive adult patients in resource limited settings without virological monitoring: a retrospective analysis of DART trial data.

Dolling DI, Goodall RL, Chirara M, Hakim J, Nkurunziza P, Munderi P, Eram D, Tumukunde D, Spyer MJ, Gilks CF, Kaleebu P, Dunn DT, Pillay D, DART Virology Group.

2017-02-214 citations

10.1186/s12879-017-2266-3

High Level of Viral Suppression and Low Switch Rate to Second-Line Antiretroviral Therapy among HIV-Infected Adult Patients Followed over Five Years: Retrospective Analysis of the DART Trial

Cissy Kityo, Diana M. Gibb, Charles F. Gilks, Ruth Goodall, Ivan Mambule et al. (12 authors)

PLoS ONE2014-03-139 citations

10.1371/journal.pone.0090772

Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial.

Gibb DM, Kizito H, Russell EC, Chidziva E, Zalwango E, Nalumenya R, Spyer M, Tumukunde D, Nathoo K, Munderi P, Kyomugisha H, Hakim J, Grosskurth H, Gilks CF, Walker AS, Musoke P, DART trial team.

2012-05-15102 citations

10.1371/journal.pmed.1001217

Cost effectiveness analysis of clinically driven versus routine laboratory monitoring of antiretroviral therapy in Uganda and Zimbabwe.

Medina Lara A, Kigozi J, Amurwon J, Muchabaiwa L, Nyanzi Wakaholi B, Mujica Mota RE, Walker AS, Kasirye R, Ssali F, Reid A, Grosskurth H, Babiker AG, Kityo C, Katabira E, Munderi P, Mugyenyi P, Hakim J, Darbyshire J, Gibb DM, Gilks CF, DART Trial Team.

2012-04-2423 citations

10.1371/journal.pone.0033672

Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort.

Walker AS, Ford D, Gilks CF, Munderi P, Ssali F, Reid A, Katabira E, Grosskurth H, Mugyenyi P, Hakim J, Darbyshire JH, Gibb DM, Babiker AG.

2010-03-2794 citations

10.1016/s0140-6736(10)60057-8

Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.

DART Trial Team, Mugyenyi P, Walker AS, Hakim J, Munderi P, Gibb DM, Kityo C, Reid A, Grosskurth H, Darbyshire JH, Ssali F, Bray D, Katabira E, Babiker AG, Gilks CF, Grosskurth H, Munderi P, Kabuye G, Nsibambi D, Kasirye R, Zalwango E, Nakazibwe M, Kikaire B, Nassuna G, Massa R, Fadhiru K, Namyalo M, Zalwango A, Generous L, Khauka P, Rutikarayo N, Nakahima W, Mugisha A, Todd J, Levin J, Muyingo S, Ruberantwari A, Kaleebu P, Yirrell D, Ndembi N, Lyagoba F, Hughes P, Aber M, Lara AM, Foster S, Amurwon J, Wakholi BN, Whitworth J, Wangati K, Amuron B, Kajungu D, Nakiyingi J, Omony W, Fadhiru K, Nsibambi D, Khauka P, Mugyenyi P, Kityo C, Ssali F, Tumukunde D, Otim T, Kabanda J, Musana H, Akao J, Kyomugisha H, Byamukama A, Sabiiti J, Komugyena J, Wavamunno P, Mukiibi S, Drasiku A, Byaruhanga R, Labeja O, Katundu P, Tugume S, Awio P, Namazzi A, Bakeinyaga GT, Katabira H, Abaine D, Tukamushaba J, Anywar W, Ojiambo W, Angweng E, Murungi S, Haguma W, Atwiine S, Kigozi J, Namale L, Mukose A, Mulindwa G, Atwiine D, Muhwezi A, Nimwesiga E, Barungi G, Takubwa J, Murungi S, Mwebesa D, Kagina G, Mulindwa M, Ahimbisibwe F, Mwesigwa P, Akuma S, Zawedde C, Nyiraguhirwa D, Tumusiime C, Bagaya L, Namara W, Kigozi J, Karungi J, Kankunda R, Enzama R, Latif A, Hakim J, Robertson V, Reid A, Chidziva E, Bulaya-Tembo R, Musoro G, Taziwa F, Chimbetete C, Chakonza L, Mawora A, Muvirimi C, Tinago G, Svovanapasis P, Simango M, Chirema O, Machingura J, Mutsai S, Phiri M, Bafana T, Chirara M, Muchabaiwa L, Muzambi M, Mutowo J, Chivhunga T, Chigwedere E, Pascoe M, Warambwa C, Zengeza E, Mapinge F, Makota S, Jamu A, Ngorima N, Chirairo H, Chitsungo S, Chimanzi J, Maweni C, Warara R, Matongo M, Mudzingwa S, Jangano M, Moyo K, Vere L, Mdege N, Machingura I, Katabira E, Ronald A, Kambungu A, Lutwama F, Mambule I, Nanfuka A, Walusimbi J, Nabankema E, Nalumenya R, Namuli T, Kulume R, Namata I, Nyachwo L, Florence A, Kusiima A, Lubwama E, Nairuba R, Oketta F, Buluma E, Waita R, Ojiambo H, Sadik F, Wanyama J, Nabongo P, Oyugi J, Sematala F, Muganzi A, Twijukye C, Byakwaga H, Ochai R, Muhweezi D, Coutinho A, Etukoit B, Gilks C, Boocock K, Puddephatt C, Grundy C, Bohannon J, Winogron D, Gibb DM, Burke A, Bray D, Babiker A, Walker AS, Wilkes H, Rauchenberger M, Sheehan S, Spencer-Drake C, Taylor K, Spyer M, Ferrier A, Naidoo B, Dunn D, Goodall R, Darbyshire JH, Peto L, Nanfuka R, Mufuka-Kapuya C, Kaleebu P, Pillay D, Robertson V, Yirrell D, Tugume S, Chirara M, Katundu P, Ndembi N, Lyagoba F, Dunn D, Goodall R, McCormick A, Lara AM, Foster S, Amurwon J, Wakholi BN, Kigozi J, Muchabaiwa L, Muzambi M, Weller I, Babiker A, Bahendeka S, Bassett M, Wapakhabulo AC, Darbyshire JH, Gazzard B, Gilks C, Grosskurth H, Hakim J, Latif A, Mapuchere C, Mugurungi O, Mugyenyi P, Burke C, Jones S, Newland C, Pearce G, Rahim S, Rooney J, Smith M, Snowden W, Steens JM, Breckenridge A, McLaren A, Hill C, Matenga J, Pozniak A, Serwadda D, Peto T, Palfreeman A, Borok M, Katabira E.

2009-12-08221 citations

10.1016/s0140-6736(09)62067-5

Interventions

Randomisation to Clinical Monitoring Only (CMO) or Laboratory and Clinical Monitoring (LCM): 3300 patients will be randomised to CMO or LCM over a period of 1-2 years. Randomisation will be stratified

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Documentation of HIV-1 infection: antibody positive serology by enzyme-linked immunosorbent assay (ELISA) test (confirmed by licensed second ELISA or Western Blot) 2. Age =18 years 3. Symptomatic WHO stage 2, 3 or 4 HIV disease and CD4 <200 cells/mm3 4. ART naïve (except for ART use during pregnancy for the prevention of mother-to-child HIV transmission) 5. Agreement and documented informed consent to be randomised to CMO or LCM and to STI or continuous ART, if eligible 6. Life expectancy of at least 3 months

Exclusion criteria

Exclusion criteria: 1. Cannot or unlikely to attend regularly (e.g. usual residence too far from Study Centre) 2. Likelihood of poor compliance 3. Presence of acute infection (e.g. malaria, acute hepatitis, pneumococcal pneumonia, non-typhoid salmonella septicaemia, cryptococcal meningitis). Patients may be admitted after recovery of an acute infection. Patients with tuberculosis (TB) will not be enrolled while on the intensive phase of anti-tuberculosis therapy, but should be re-evaluated after the intensive phase and a decision made then about starting ART. Patients starting ART whilst on anti-tuberculosis therapy after the intensive phase will not receive NVP, nor will they be randomised into the NORA substudy. 4. On chemotherapy for malignancy 5. Laboratory abnormalities which are a contraindication for the patient to start ART (e.g. haemoglobin 5 x the upper limit of normal [ULN], grade 3 renal dysfunction - creatinine >360 µmol/l and/or urea >5 x ULN) 6. Pregnancy or breastfeeding

Design outcomes

Primary

Measure	Time frame
1. Efficacy: Progression to a new WHO stage 4 HIV event or death 2. Safety: Any serious adverse event, which is not HIV related	—

Secondary

Measure	Time frame
1. Progression to a new or recurrent WHO stage 4 HIV event or death 2. Progression to a new WHO stage 4 HIV event or death from 6 weeks after randomisation 3. Progression to a new or recurrent WHO stage 4 HIV event or death from 6 weeks after randomisation 4. Any grade 3 or 4 adverse events 5. Number and class of anti-HIV drugs received by 3 years 6. Time to cessation of first-line regimen for failure 7. Adherence as measured by questionnaire and pill counts 8. CD4 count at 3 years (provided that it is at least 2 months after restarting ART for those in the STI group) 9. HIV RNA viral load (performed retrospectively) at 3 years (providing that it is at least 2 months after restarting ART for those in the STI group) 10. HIV resistance profiles at 3 years in those with detectable viral load (providing that it is at least 2 months after restarting ART for those in the STI group)	—

Measure

Time frame

1. Progression to a new or recurrent WHO stage 4 HIV event or death 2. Progression to a new WHO stage 4 HIV event or death from 6 weeks after randomisation 3. Progression to a new or recurrent WHO stage 4 HIV event or death from 6 weeks after randomisation 4. Any grade 3 or 4 adverse events 5. Number and class of anti-HIV drugs received by 3 years 6. Time to cessation of first-line regimen for failure 7. Adherence as measured by questionnaire and pill counts 8. CD4 count at 3 years (provided that it is at least 2 months after restarting ART for those in the STI group) 9. HIV RNA viral load (performed retrospectively) at 3 years (providing that it is at least 2 months after restarting ART for those in the STI group) 10. HIV resistance profiles at 3 years in those with detectable viral load (providing that it is at least 2 months after restarting ART for those in the STI group)

—

Countries

Uganda, Zimbabwe

Outcome results

None listed