An observational study in an urban Ugandan clinic comparing virological outcomes of patients switched from first-line antiretroviral regimens to second-line regimens containing ritonavir-boosted atazanavir or ritonavir-boosted lopinavir.

BACKGROUND: The World Health Organisation approved boosted atazanavir as a preferred second line protease inhibitor in 2010. This is as an alternative to the current boosted lopinavir. Atazanavir has a lower genetic barrier than lopinavir. We compared the virological outcomes of patients during the roll out of routine viral load monitoring, who had switched to boosted second- line regimens of either atazanavir or lopinavir. METHODS: This was a cross-sectional study involving adult patients at the Infectious Diseases Institute Kampala, Uganda started on a standard WHO recommended second-line regimen containing either boosted atazanavir or boosted lopinavir between 1 Dec 2014 and 31 July 2015.. Mantel -Haenszel chi square was used to test for the statistical significance of the odds of being suppressed (VL < 400 copies/ml) when on boosted atazanavir compared to boosted lopinavir after stratifying by duration on antiretroviral therapy (ART). Multivariate logistic regression analysis used to determine if the type of boosted protease inhibitor (bPI) was associated with virological outcome. RESULTS: Ninety (90) % on ATV/r and 83% on LPV/r had a VL less than 1000 copies/ml. The odds of being suppressed using the same viral load cut-off while on boosted atazanavir compared to boosted lopinavir was not statistically significant after stratifying for duration on ART (p = 0.09). In a multivariate analysis the type of bPI used was not a predictor of virological outcome (p = 0.60). CONCLUSIONS: Patients using the WHO recommended second-line of boosted atazanavir have comparable virological suppression to those on boosted lopinavir

Boosted lopinavir vs boosted atazanavir in patients failing a NNRTI first line regimen in an urban clinic in Kampala.

INTRODUCTION: In 2011 Uganda recommended boosted atazanavir (ATV/r) as the preferred PI for second line due to once daily dosing, replacing aluvia (LPV/r) (1, 2). The evidence was based on the BMS O45 trial, of LPV/r vs ATV/r was performed in a high-income setting, on patients with prior PI use and resistance testing (2, 3). There are no RCTs or observational studies comparing use of ATV/r with LPV/r in patients failing NNRTI first line antiretroviral therapy in sub-Saharan Africa (3, 4). The Infectious Diseases Institute (IDI) has a large second line cohort (>1838). This aims to compare clinical, immunologic and virologic response of LPV/r versus ATV/r at IDI. METHODS: Retrospective cohort analysis on routinely collected data of patients switched to second line with NRTI backbones TDF/3TC or FTC, AZT/3TC, ABC/3TC from January 2009 to December 2013. Students T-tests and Chi-square tests were used in this analysis. RESULTS: A total of 1286 (73.5% female) patients were switched to LPV/r 991 (77%) and ATV/r 295 (23%) (p<0.001). NRTI backbones were 760 on TDF/3TC (66.8% LPV/r vs 33.2% on ATV/r), 504 on AZT/3TC (93.3% vs 6.7%), and 22 on ABC/3TC (59% vs 41%). Median (IQR) time on first line for LPV/r was 21 (1-44) months and for ATV/r was 41 months (22-68). Median CD4 (IQR) at switch to LPV/r was 181 cells/uL (66-424) and to ATV/r was 122 (57-238) (p≤0.001). A total of 366 patients had CD4 done at six months after switch and the mean (IQR) CD4 increase was 153 (54-241) for LPV/r versus 116 (52-171) for ATV/r (p=0.232). Additionally, 304 had a CD4 at 12 months and the means were 172 (45-272) for LPV/r vs 179 (60-271) for ATV/r (p=0.426). There was no significant difference in the mean increment by NRTI backbone or by stratifying to viral load (VL) at time of switch to VL <100,000 and ≥100,000. Median (IQR) VL at switch was 61,000 (13,000-2,030,000) LPV/r and 51,000 (14,000_151,000) ATV/r. 269 had a VL done in the first 12 months and 178/250 (71.2%) on LPV/r versus 16/19 (84.2%) on ATV/r were undetectable (p=0.228). 259 (26%) LPV/r versus 33(11%) ATV/r had ≥1 opportunistic infections on second line (p<0.001). CONCLUSIONS: This is an observational study based on our experience at IDI. Like elsewhere in Africa, there is no routine viral load testing, making it difficult to get sensitive analysis of data on ART efficacy within routine clinical practice. Nevertheless, this observational study is reassuring in terms of efficacy of both ATV/r and LPV/r for patients failing first line therapy in our setting

An observational study in an urban Ugandan clinic comparing virological outcomes of patients switched from first-line antiretroviral regimens to second-line regimens containing ritonavir-boosted atazanavir or ritonavir-boosted lopinavir.

BACKGROUND: The World Health Organisation approved boosted atazanavir as a preferred second line protease inhibitor in 2010. This is as an alternative to the current boosted lopinavir. Atazanavir has a lower genetic barrier than lopinavir. We compared the virological outcomes of patients during the roll out of routine viral load monitoring, who had switched to boosted second- line regimens of either atazanavir or lopinavir. METHODS: This was a cross-sectional study involving adult patients at the Infectious Diseases Institute Kampala, Uganda started on a standard WHO recommended second-line regimen containing either boosted atazanavir or boosted lopinavir between 1 Dec 2014 and 31 July 2015.. Mantel -Haenszel chi square was used to test for the statistical significance of the odds of being suppressed (VL < 400 copies/ml) when on boosted atazanavir compared to boosted lopinavir after stratifying by duration on antiretroviral therapy (ART). Multivariate logistic regression analysis used to determine if the type of boosted protease inhibitor (bPI) was associated with virological outcome. RESULTS: Ninety (90) % on ATV/r and 83% on LPV/r had a VL less than 1000 copies/ml. The odds of being suppressed using the same viral load cut-off while on boosted atazanavir compared to boosted lopinavir was not statistically significant after stratifying for duration on ART (p = 0.09). In a multivariate analysis the type of bPI used was not a predictor of virological outcome (p = 0.60). CONCLUSIONS: Patients using the WHO recommended second-line of boosted atazanavir have comparable virological suppression to those on boosted lopinavir

Prevalence of overweight and obesity among adolescents living with HIV after dolutegravir - based antiretroviral therapy start in Kampala, Uganda

Abstract Background Dolutegravir (DTG)-based antiretroviral therapy (ART) is currently the preferred first-line treatment for persons living with HIV (PLHIV) including children and adolescents in many low- and middle-income countries including Uganda. However, there are concerns about excessive weight gain associated with DTG especially in adults. There remains paucity of current information on weight-related outcomes among adolescents on DTG. We determined the prevalence of excessive weight gain and associated factors among adolescents living with HIV (ALHIV) receiving DTG-based ART in Kampala, Uganda. Methods Cross-sectional study involving ALHIV aged 10–19 years on DTG-based ART for at least one year were recruited from public health facilities in Kampala between February and May 2022. Excessive weight gain was defined as becoming overweight or obese per body mass index (BMI) norms while on DTG-based ART for at least one year. Demographic, clinical and laboratory data were collected using interviewer-administered questionnaires and data extracted from medical records. At enrolment, blood pressure and anthropometry were measured and blood was drawn for blood glucose and lipid profile. Data was summarised using descriptive statistics and logistic regression was performed to determine the associated factors. Results We enrolled 165 ALHIV with a median age of 14 years (IQR 12–16). Eighty (48.5%) were female. The median duration on ART and DTG was 8 years (IQR 7–11) and 2 years (IQR 1–3) respectively. At DTG initiation, the majority of participants (152/165, 92.1%) were ART-experienced, and had normal BMI (160/165, 97%). Overall, 12/165 (7.3%) adolescents (95% CI: 4.2–12.4) had excessive weight gain. No factors were significantly associated with excessive weight gain after DTG start in ALHIV. However, all ALHIV with excessive weight gain were females. Conclusion Our study found a prevalence of 7.3% of overweight and obesity in ALHIV after initiating DTG. We did not find any factor significantly associated with excessive weight gain in ALHIV on DTG. Nonetheless, we recommend ongoing routine monitoring of anthropometry and metabolic markers in ALHIV as DTG use increases globally, to determine the exact magnitude of excessive weight gain and to identify those at risk of becoming overweight or obese while taking the medication

High willingness to use injectable antiretroviral therapy among women who have been lost to follow-up from HIV programmes: A nested cross-sectional study.

OBJECTIVES: Efforts to achieve zero transmission of HIV to infants born to women living with HIV in sub-Saharan African are undermined by high rates of loss to follow-up in prevention of vertical transmission (PVT) programmes. The fear of HIV status disclosure through the discovery of pill bottles at home is a major contributor. Injectable antiretroviral therapy (ART) has proved to be efficacious in clinical trials and is discreet, offering a potential solution. We investigated the knowledge and willingness to use injectable ART among women who were lost to follow-up from the PVT programme in Uganda. METHODS: Women were traced by nurse counsellors and knowledge and opinions relating to injectable ART, including willingness to use it when it becomes available, were collected. Generalized linear models were used to determine predictors of willingness to use injectable ART. CONCLUSIONS: Among 1023 women registered between 2017 and 2019 under the PVT programmes in Kampala and Wakiso districts, Uganda, 385 (38%) were lost to follow-up from care and 22% of these (83/385) were successfully traced and interviewed. Only 25% (21/83) had heard of injectable ART. Over half (55%, 46/83) were very willing to use injectable ART, 40% (33/83) were somewhat willing and four (5%) were not willing. Those who associated ART tablets with disclosure risk were more willing to consider injectable ART (adjusted odds ratio = 4.21; 95% confidence interval: 1.45-12.19; p = 0.008). We report high willingness to use injectable ART associated with fears that ART tablets were a potential source of HIV status disclosure. Injectable ART could be a solution for women who have challenges with disclosure

Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults

Abstract Background The Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to months of exposure to DTG. Having demonstrated a low incidence of diabetes mellitus and improving blood glucose trajectories in a cohort of ART naïve Ugandan PWH on DTG, we sought to determine whether the observed improvement in blood glucose did not mask background compensated insulin resistance. Methods In this analysis, 63 patients underwent serial oral glucose tolerance tests over 48 weeks. Using fasting serum insulin and glucose, we calculated insulin resistance and pancreatic beta cell function by homeostatic modelling (HOMA IR and HOMA%β respectively). Absolute mean changes between baseline and post-baseline blood glucose, pancreatic beta cell function and insulin resistance were computed by subtracting each post-baseline value from the baseline value and compared using student t-test. Multiple linear regression models were used to determine the factors associated with changes in pancreatic beta cell function and insulin resistance. Results Of the 63 participants, 37 (58%) were female. Median age was 31 (IQR: 28–37). Despite a trend towards an initial increase in both HOMA IR and HOMA%β at 12 weeks followed by a decline through 36 weeks to 48 weeks, the HOMA IR and HOMA%β at 48 weeks were not significantly different from baseline i.e. (difference in mean HOMA IR from baseline: 0.14, 95%CI: -0.46, 0.733, p = 0.648) and (difference in mean HOMA %β from baseline: 6.7, 95%CI: -13.4, 26.8, p = 0.506) respectively. Conclusion We demonstrated insignificant changes in both insulin resistance and pancreatic beta cell function in clinically stable young adult Ugandan PWH on dolutegravir for 48 weeks. We add to the body of evidence demonstrating glucose metabolic safety of dolutegravir in ART naïve patients. Ugandan guidelines should reconsider restricting DTG initiation in ART naive adults at high risk for diabetes

Two-drug regimens for the treatment of HIV in Africa

Two-drug regimens (2DR) for the treatment of HIV are increasingly available. The oral regimen of dolutegravir and lamivudine is recommended as a preferred option in multiple national guidelines but is not currently included in WHO HIV treatment guidelines nor widely used in Africa. Long-acting injectable cabotegravir and rilpivirine is being rolled out in USA, Europe, and Australia but use in sub-Saharan Africa is currently limited to clinical trials. Given increasing life expectancy, rising prevalence of non-communicable diseases, and resulting polypharmacy among people living with HIV (PLWH), there are potential advantages to the use of 2DR in this setting. However, 2DR are not suitable for all. Data on the use of 2DR in PLWH in Africa are limited and further studies are needed to inform policy. In this article we review existing evidence and highlight the risks, benefits, and key knowledge gaps for the use of 2DR in programmatic care settings