Journal Article > Meta-AnalysisFull Text
Lancet HIV. 2015 August 11; Volume 2 (Issue 10); DOI:10.1016/S2352-3018(15)00137-X
Ford NP, Shubber Z, Meintjes GA, Grinsztejn B, Eholie SP, et al.
Lancet HIV. 2015 August 11; Volume 2 (Issue 10); DOI:10.1016/S2352-3018(15)00137-X
Journal Article > CommentaryFull Text
Lancet HIV. 2018 September 8; Volume 392 (Issue 10150); 797-798.; DOI:10.1016/S0140-6736(18)31670-2
Reuter A, Furin J
Lancet HIV. 2018 September 8; Volume 392 (Issue 10150); 797-798.; DOI:10.1016/S0140-6736(18)31670-2
Journal Article > CommentaryFull Text
Lancet HIV. 2021 December 7; Volume S2352-3018 (Issue 21); 00321-0.; DOI:10.1016/S2352-3018(21)00321-0
Barber M, Sarpatwari A, Cepuch C
Lancet HIV. 2021 December 7; Volume S2352-3018 (Issue 21); 00321-0.; DOI:10.1016/S2352-3018(21)00321-0
Journal Article > CommentaryFull Text
Lancet HIV. 2024 August 21; Online ahead of print; DOI:10.1016/S2352-3018(24)00207-8
Flores A, Tut Chol B, Alphonse J, Hewett T
Lancet HIV. 2024 August 21; Online ahead of print; DOI:10.1016/S2352-3018(24)00207-8
Journal Article > CommentaryFull Text
Lancet HIV. 2020 July 2; DOI:32621871
Reuter A, Furin J
Lancet HIV. 2020 July 2; DOI:32621871
“We were hungry all the time”, is the first thing a 28-year-old tuberculosis survivor from rural Haiti told one of us (JF) when asked in 2017 about his experience of being treated for the disease. This patient had been cutting sugar cane to support his family of seven—all of whom lived in a one-room shack—but had to stop his gruelling labour once he became sick with tuberculosis, both because of his physical symptoms and because he had to go to the clinic daily for directly observed therapy. Without his income, his family fell into ruin and the pressing need to feed his children became his most urgent priority. “It was hard to take my treatment when the little ones were holding their bellies and crying. We lost so much to TB.”
Journal Article > CommentaryFull Text
Lancet HIV. 2015 September 24; Volume 2 (Issue 10); DOI:10.1016/S2352-3018(15)00180-0
Isaakidis P, Gupta S, Das M, Ferrer D, Nalinikanta R, et al.
Lancet HIV. 2015 September 24; Volume 2 (Issue 10); DOI:10.1016/S2352-3018(15)00180-0
Journal Article > ResearchFull Text
Lancet HIV. 2023 May 22; Volume S2352-3018 (Issue 23); 00081-4.; DOI:10.1016/S2352-3018(23)00081-4
Griesel R, Zhao Y, Simmons B, Omar Z, Wiesner L, et al.
Lancet HIV. 2023 May 22; Volume S2352-3018 (Issue 23); 00081-4.; DOI:10.1016/S2352-3018(23)00081-4
BACKGROUND
The drug-drug interaction between rifampicin and dolutegravir can be overcome by supplemental dolutegravir dosing, which is difficult to implement in high-burden settings. We aimed to test whether virological outcomes with standard-dose dolutegravir-based antiretroviral therapy (ART) are acceptable in people with HIV on rifampicin-based antituberculosis therapy.
METHODS
RADIANT-TB was a phase 2b, randomised, double-blind, non-comparative, placebo-controlled trial at a single site in Khayelitsha, Cape Town, South Africa. Participants were older than 18 years of age, with plasma HIV-1 RNA greater than 1000 copies per mL, CD4 count greater than 100 cells per μL, ART-naive or first-line ART interrupted, and on rifampicin-based antituberculosis therapy for less than 3 months. By use of permuted block (block size of 6) randomisation, participants were assigned (1:1) to receive either tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus supplemental 50 mg dolutegravir 12 h later or tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus matched placebo 12 h later. Participants received standard antituberculosis therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol for the first 2 months followed by isoniazid and rifampicin for 4 months). The primary outcome was the proportion of participants with virological suppression (HIV-1 RNA <50 copies per mL) at week 24 analysed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03851588.
FINDINGS
Between Nov 28, 2019, and July 23, 2021, 108 participants (38 female, median age 35 years [IQR 31-40]) were randomly assigned to supplemental dolutegravir (n=53) or placebo (n=55). Median baseline CD4 count was 188 cells per μL (IQR 145-316) and median HIV-1 RNA was 5·2 log10 copies per mL (4·6-5·7). At week 24, 43 (83%, 95% CI 70-92) of 52 participants in the supplemental dolutegravir arm and 44 (83%, 95% CI 70-92) of 53 participants in the placebo arm had virological suppression. No treatment-emergent dolutegravir resistance mutations were detected up to week 48 in the 19 participants with study-defined virological failure. Grade 3 and 4 adverse events were similarly distributed between the study arms. The most frequent grade 3 and 4 adverse events were weight loss (4/108 [4%]), insomnia (3/108 [3%]), and pneumonia (3/108 [3%]).
INTERPRETATION
Our findings suggest that twice-daily dolutegravir might be unnecessary in people with HIV-associated tuberculosis.
The drug-drug interaction between rifampicin and dolutegravir can be overcome by supplemental dolutegravir dosing, which is difficult to implement in high-burden settings. We aimed to test whether virological outcomes with standard-dose dolutegravir-based antiretroviral therapy (ART) are acceptable in people with HIV on rifampicin-based antituberculosis therapy.
METHODS
RADIANT-TB was a phase 2b, randomised, double-blind, non-comparative, placebo-controlled trial at a single site in Khayelitsha, Cape Town, South Africa. Participants were older than 18 years of age, with plasma HIV-1 RNA greater than 1000 copies per mL, CD4 count greater than 100 cells per μL, ART-naive or first-line ART interrupted, and on rifampicin-based antituberculosis therapy for less than 3 months. By use of permuted block (block size of 6) randomisation, participants were assigned (1:1) to receive either tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus supplemental 50 mg dolutegravir 12 h later or tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus matched placebo 12 h later. Participants received standard antituberculosis therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol for the first 2 months followed by isoniazid and rifampicin for 4 months). The primary outcome was the proportion of participants with virological suppression (HIV-1 RNA <50 copies per mL) at week 24 analysed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03851588.
FINDINGS
Between Nov 28, 2019, and July 23, 2021, 108 participants (38 female, median age 35 years [IQR 31-40]) were randomly assigned to supplemental dolutegravir (n=53) or placebo (n=55). Median baseline CD4 count was 188 cells per μL (IQR 145-316) and median HIV-1 RNA was 5·2 log10 copies per mL (4·6-5·7). At week 24, 43 (83%, 95% CI 70-92) of 52 participants in the supplemental dolutegravir arm and 44 (83%, 95% CI 70-92) of 53 participants in the placebo arm had virological suppression. No treatment-emergent dolutegravir resistance mutations were detected up to week 48 in the 19 participants with study-defined virological failure. Grade 3 and 4 adverse events were similarly distributed between the study arms. The most frequent grade 3 and 4 adverse events were weight loss (4/108 [4%]), insomnia (3/108 [3%]), and pneumonia (3/108 [3%]).
INTERPRETATION
Our findings suggest that twice-daily dolutegravir might be unnecessary in people with HIV-associated tuberculosis.
Journal Article > CommentaryFull Text
Lancet HIV. 2016 February 2; Volume 3 (Issue 3); DOI:10.1016/S2352-3018(16)00002-3
Furin J, Isaakidis P
Lancet HIV. 2016 February 2; Volume 3 (Issue 3); DOI:10.1016/S2352-3018(16)00002-3
Journal Article > CommentaryAbstract Only
Lancet HIV. 2022 April 1; Volume 9 (Issue 4); e224-e225.; DOI:10.1016/S2352-3018(22)00008-X
Reuter A, Furin J
Lancet HIV. 2022 April 1; Volume 9 (Issue 4); e224-e225.; DOI:10.1016/S2352-3018(22)00008-X
Vika began to tremble uncontrollably as the car her family spent their entire savings on approached the hospital. Although she willed herself to stop, her emaciated frame shook with the fear of what lay ahead. The hospital was, after all, where people in her village went to die. She could not remember the last person who went there and came home well. Vika had felt sick for a long time, with fevers, weight loss, and a pain in her side that never seemed to go away. She had returned home from the city after her husband and baby daughter died, and she had hoped the fresher air might do her some good. Now, she found herself winding her way along a bumpy road on what she feared might be the last trip she would make in her young life (Vika's real name has been changed to protect her privacy).
Journal Article > ResearchAbstract
Lancet HIV. 2015 August 3; Volume 2 (Issue 9); E368-75.; DOI:10.1016/S2352-3018(15)00113-7
Cornell M, Johnson LF, Schomaker M, Tanser F, Maskew M, et al.
Lancet HIV. 2015 August 3; Volume 2 (Issue 9); E368-75.; DOI:10.1016/S2352-3018(15)00113-7
BACKGROUND
As access to antiretroviral therapy (ART) expands, increasing numbers of older patients will start treatment and need specialised long-term care. However, the effect of age in ART programmes in resource-constrained settings is poorly understood. The HIV epidemic is ageing rapidly and South Africa has one of the highest HIV population prevalences worldwide. We explored the effect of age on mortality of patients on ART in South Africa and whether this effect is mediated by baseline immunological status.
METHODS
In this retrospective cohort analysis, we studied HIV-positive patients aged 16-80 years who started ART for the first time in six large South African cohorts of the International Epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, in KwaZulu-Natal, Gauteng, and Western Cape (two primary care clinics, three hospitals, and a large rural cohort). The primary outcome was mortality. We ascertained patients' vital status through linkage to the National Population Register. We used inverse probability weighting to correct mortality for loss to follow-up. We estimated mortality using Cox's proportional hazards and competing risks regression. We tested the interaction between baseline CD4 cell count and age.
FINDINGS
Between Jan 1, 2004, and Dec 31, 2013, 84,078 eligible adults started ART. Of these, we followed up 83,566 patients for 174,640 patient-years. 8% (1817 of 23,258) of patients aged 16-29 years died compared with 19% (93 of 492) of patients aged 65 years or older. The age adjusted mortality hazard ratio was 2·52 (95% CI 2·01-3·17) for people aged 65 years or older compared with those 16-29 years of age. In patients starting ART with a CD4 count of less than 50 cells per μL, the adjusted mortality hazard ratio was 2·52 (2·04-3·11) for people aged 50 years or older compared with those 16-39 years old. Mortality was highest in patients with CD4 counts of less than 50 cells per μL, and 15% (1103 of 7295) of all patients aged 50 years or older starting ART were in this group. The proportion of patients aged 50 years or older enrolling in ART increased with successive years, from 6% (290 of 4999) in 2004 to 10% (961 of 9657) in 2012-13, comprising 9% of total enrolment (7295 of 83 566). At the end of the study, 6304 (14%) of 44,909 patients still alive and in care were aged 50 years or older.
INTERPRETATION
Health services need reorientation towards HIV diagnosis and starting of ART in older individuals. Policies are needed for long-term care of older people with HIV.
As access to antiretroviral therapy (ART) expands, increasing numbers of older patients will start treatment and need specialised long-term care. However, the effect of age in ART programmes in resource-constrained settings is poorly understood. The HIV epidemic is ageing rapidly and South Africa has one of the highest HIV population prevalences worldwide. We explored the effect of age on mortality of patients on ART in South Africa and whether this effect is mediated by baseline immunological status.
METHODS
In this retrospective cohort analysis, we studied HIV-positive patients aged 16-80 years who started ART for the first time in six large South African cohorts of the International Epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, in KwaZulu-Natal, Gauteng, and Western Cape (two primary care clinics, three hospitals, and a large rural cohort). The primary outcome was mortality. We ascertained patients' vital status through linkage to the National Population Register. We used inverse probability weighting to correct mortality for loss to follow-up. We estimated mortality using Cox's proportional hazards and competing risks regression. We tested the interaction between baseline CD4 cell count and age.
FINDINGS
Between Jan 1, 2004, and Dec 31, 2013, 84,078 eligible adults started ART. Of these, we followed up 83,566 patients for 174,640 patient-years. 8% (1817 of 23,258) of patients aged 16-29 years died compared with 19% (93 of 492) of patients aged 65 years or older. The age adjusted mortality hazard ratio was 2·52 (95% CI 2·01-3·17) for people aged 65 years or older compared with those 16-29 years of age. In patients starting ART with a CD4 count of less than 50 cells per μL, the adjusted mortality hazard ratio was 2·52 (2·04-3·11) for people aged 50 years or older compared with those 16-39 years old. Mortality was highest in patients with CD4 counts of less than 50 cells per μL, and 15% (1103 of 7295) of all patients aged 50 years or older starting ART were in this group. The proportion of patients aged 50 years or older enrolling in ART increased with successive years, from 6% (290 of 4999) in 2004 to 10% (961 of 9657) in 2012-13, comprising 9% of total enrolment (7295 of 83 566). At the end of the study, 6304 (14%) of 44,909 patients still alive and in care were aged 50 years or older.
INTERPRETATION
Health services need reorientation towards HIV diagnosis and starting of ART in older individuals. Policies are needed for long-term care of older people with HIV.