Who’s slipping through the cracks? A comprehensive individual, clinical and health system characterization of people with virological failure on first‐line HIV treatment in Uganda and South Africa

Among those with HIV, anemia is a strong risk factor for disease progression and death independent of CD4 count and viral load. Understanding the role of anemia in HIV treatment is critical to developing strategies to reduce morbidity and mortality. We conducted a prospective analysis among 10,259 HIV-infected adults initiating first-line ART between April 2004 and August 2009 in Johannesburg, South Africa. The prevalence of anemia at ART initiation was 25.8%. Mean hemoglobin increased independent of baseline CD4. Females, lower BMI, WHO stage III/IV, lower CD4 count, and zidovudine use were associated with increased risk of developing anemia during follow-up. After initiation of ART, hemoglobin improved, regardless of regimen type and the degree of immunosuppression. Between 0 and 6 months on ART, the magnitude of hemoglobin increase was linearly related to CD4 count. However, between 6 and 24 months on ART, hemoglobin levels showed a sustained overall increase, the magnitude of which was similar regardless of baseline CD4 level. This increase in hemoglobin was seen even among patients on zidovudine containing regimens. Since low hemoglobin is an established adverse prognostic marker, prompt identification of anemia may result in improved morbidity and mortality of patients initiating ART.

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High-Levels of Acquired Drug Resistance in Adult Patients Failing First-Line Antiretroviral Therapy in a Rural HIV Treatment Programme in KwaZulu-Natal, South Africa

PLoS ONE ◽

10.1371/journal.pone.0072152 ◽

2013 ◽

Vol 8 (8) ◽

pp. e72152 ◽

Cited By ~ 36

Author(s):

Justen Manasa ◽

Richard J. Lessells ◽

Andrew Skingsley ◽

Kevindra K. Naidu ◽

Marie-Louise Newell ◽

...

Keyword(s):

South Africa ◽

Drug Resistance ◽

Antiretroviral Therapy ◽

Hiv Treatment ◽

Adult Patients ◽

Treatment Programme ◽

First Line ◽

Acquired Drug Resistance ◽

Kwazulu Natal

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Treatment options after virological failure of first-line tenofovir-based regimens in South Africa

AIDS ◽

10.1097/qad.0000000000001033 ◽

2016 ◽

Vol 30 (7) ◽

pp. 1137-1140 ◽

Cited By ~ 11

Author(s):

Maria Casadellà ◽

Marc Noguera-Julian ◽

Henry Sunpath ◽

Michelle Gordon ◽

Cristina Rodriguez ◽

...

Keyword(s):

South Africa ◽

Virological Failure ◽

Treatment Options ◽

First Line

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Medication Side Effects and Retention in HIV Treatment: A Regression Discontinuity Study of Tenofovir Implementation in South Africa and Zambia

American Journal of Epidemiology ◽

10.1093/aje/kwy093 ◽

2018 ◽

Vol 187 (9) ◽

pp. 1990-2001 ◽

Cited By ~ 3

Author(s):

Alana T Brennan ◽

Jacob Bor ◽

Mary-Ann Davies ◽

Gilles Wandeler ◽

Hans Prozesky ◽

...

Keyword(s):

South Africa ◽

Relative Risk ◽

Side Effects ◽

Regression Discontinuity ◽

Retention In Care ◽

Hiv Treatment ◽

Local Linear Regression ◽

First Line ◽

Percentage Points ◽

The Impact

Abstract Tenofovir is less toxic than other nucleoside reverse-transcriptase inhibitors used in antiretroviral therapy (ART) and may improve retention of human immunodeficiency virus (HIV)–infected patients on ART. We assessed the impact of national guideline changes in South Africa (2010) and Zambia (2007) recommending tenofovir for first-line ART. We applied regression discontinuity in a prospective cohort study of 52,294 HIV-infected adults initiating first-line ART within 12 months (±12 months) of each guideline change. We compared outcomes in patients presenting just before and after the guideline changes using local linear regression and estimated intention-to-treat effects on initiation of tenofovir, retention in care, and other treatment outcomes at 24 months. We assessed complier causal effects among patients starting tenofovir. The new guidelines increased the percentages of patients initiating tenofovir in South Africa (risk difference (RD) = 81 percentage points, 95% confidence interval (CI): 73, 89) and Zambia (RD = 42 percentage points, 95% CI: 38, 45). With the guideline change, the percentage of single-drug substitutions decreased substantially in South Africa (RD = −15 percentage points, 95% CI: −18, −12). Starting tenofovir also reduced attrition in Zambia (intent-to-treat RD = −1.8% (95% CI: −3.5, −0.1); complier relative risk = 0.74) but not in South Africa (RD = −0.9% (95% CI: −5.9, 4.1); complier relative risk = 0.94). These results highlight the importance of reducing side effects for increasing retention in care, as well as the differences in population impact of policies with heterogeneous treatment effects implemented in different contexts.

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Clinical outcomes after first‐line HIV treatment failure in South Africa: the next cascade of care

HIV Medicine ◽

10.1111/hiv.12877 ◽

2020 ◽

Vol 21 (7) ◽

pp. 457-462

Author(s):

CC Iwuji ◽

M Shahmanesh ◽

O Koole ◽

K Herbst ◽

D Pillay ◽

...

Keyword(s):

South Africa ◽

Treatment Failure ◽

Clinical Outcomes ◽

Hiv Treatment ◽

First Line ◽

Cascade Of Care

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Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa

AIDS Research and Therapy ◽

10.1186/s12981-021-00393-5 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Benjamin Chimukangara ◽

Richard J. Lessells ◽

Lavanya Singh ◽

Indra Grigalionyte ◽

Nonhlanhla Yende-Zuma ◽

...

Keyword(s):

South Africa ◽

Drug Resistance ◽

Sequence Data ◽

Hiv Treatment ◽

Close Monitoring ◽

Second Line ◽

First Line ◽

Treatment Regimens ◽

Kwazulu Natal ◽

Hiv 1

Abstract Background Introduction of tenofovir (TDF) plus lamivudine (3TC) and dolutegravir (DTG) in first- and second-line HIV treatment regimens in South Africa warrants characterization of acquired HIV-1 drug resistance (ADR) mutations that could impact DTG-based antiretroviral therapy (ART). In this study, we sought to determine prevalence of ADR mutations and their potential impact on susceptibility to drugs used in combination with DTG among HIV-positive adults (≥ 18 years) accessing routine care at a selected ART facility in KwaZulu-Natal, South Africa. Methods We enrolled adult participants in a cross-sectional study between May and September 2019. Eligible participants had a most recent documented viral load (VL) ≥ 1000 copies/mL after at least 6 months on ART. We genotyped HIV-1 reverse transcriptase and protease genes by Sanger sequencing and assessed ADR. We characterized the effect of ADR mutations on the predicted susceptibility to drugs used in combination with DTG. Results From 143 participants enrolled, we obtained sequence data for 115 (80%), and 92.2% (95% CI 85.7–96.4) had ADR. The proportion with ADR was similar for participants on first-line ART (65/70, 92.9%, 95% CI 84.1–97.6) and those on second-line ART (40/44, 90.9%, 95% CI 78.3–97.5), and was present for the single participant on third-line ART. Approximately 89% (62/70) of those on first-line ART had dual class NRTI and NNRTI resistance and only six (13.6%) of those on second-line ART had major PI mutations. Most participants (82%) with first-line viraemia maintained susceptibility to Zidovudine (AZT), and the majority of them had lost susceptibility to TDF (71%) and 3TC (84%). Approximately two in every five TDF-treated individuals had thymidine analogue mutations (TAMs). Conclusions Susceptibility to AZT among most participants with first-line viraemia suggests that a new second-line regimen of AZT + 3TC + DTG could be effective. However, atypical occurrence of TAMs in TDF-treated individuals suggests a less effective AZT + 3TC + DTG regimen in a subpopulation of patients. As most patients with first-line viraemia had at least low-level resistance to TDF and 3TC, identifying viraemia before switch to TDF + 3TC + DTG is important to avoid DTG functional monotherapy. These findings highlight a need for close monitoring of outcomes on new standardized treatment regimens.

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Free but fragile: Human relations amidst poverty and HIV in democratic South Africa

Oral History Journal of South Africa ◽

10.25159/2309-5792/8 ◽

2015 ◽

Vol 2 (2) ◽

pp. 85-94

Author(s):

Christina Landman

Keyword(s):

South Africa ◽

Predominantly White ◽

Black People ◽

Hiv Treatment ◽

Human Relations ◽

White People ◽

Black And White ◽

The Past ◽

Wide Range ◽

Black Township

Dullstroom-Emnotweni is the highest town in South Africa. Cold and misty, it is situated in the eastern Highveld, halfway between the capital Pretoria/Tswane and the Mozambique border. Alongside the main road of the white town, 27 restaurants provide entertainment to tourists on their way to Mozambique or the Kruger National Park. The inhabitants of the black township, Sakhelwe, are remnants of the Southern Ndebele who have lost their land a century ago in wars against the whites. They are mainly dependent on employment as cleaners and waitresses in the still predominantly white town. Three white people from the white town and three black people from the township have been interviewed on their views whether democracy has brought changes to this society during the past 20 years. Answers cover a wide range of views. Gratitude is expressed that women are now safer and HIV treatment available. However, unemployment and poverty persist in a community that nevertheless shows resilience and feeds on hope. While the first part of this article relates the interviews, the final part identifies from them the discourses that keep the black and white communities from forming a group identity that is based on equality and human dignity as the values of democracy.

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