Dyslipidemia among adult people living with HIV on dolutegravir - based antiretroviral therapy at a private tertiary hospital in Kampala, Uganda: burden and determinants.

BACKGROUND: Understanding the burden of dyslipidemia and its associated factors among adult people living with HIV on dolutegravir (DTG) based anti-retroviral therapy (ART) is critical to provide clinical guidance and risk reduction strategies in our setting. METHODS: We conducted a cross-sectional study on adult people living with HIV on DTG based ART between July and August 2022 at Mengo Hospital, a private not for profit missionary hospital owned by the Church of Uganda. Dyslipidemia was defined as: Total cholesterol (TC) ≥ 5.2 mmol/l, or high-density lipoprotein (HDL) < 1 mmol/l for men and < 1.3 mmol/l for women, or triglycerides (TG) ≥ 1.7 mmol/l, and low-density lipoprotein (LDL) ≥ 3.4 mmol/l. A participant was considered to have dyslipidemia if they had any of the lipid profile parameters in the above ranges. Socio-demographic information, clinical data and behavioral characteristics were collected. Fasting lipid profile and fasting blood glucose levels were also measured. Bivariate and multivariate analyses were done using a generalized linear model regression of the Poisson family with a log link (modified Poisson) using robust standard errors since the prevalence of dyslipidemia was more than 10%. Adjusted prevalence ratios (PR) were reported with their 95% confidence intervals (CI). A p-value of less than 0.05 was considered statistically significant. RESULTS: A total of 341 participants were included. The prevalence of dyslipidemia was 78.0%, (95%CI:73.3-82.1). The highest prevalence was for low HDL (72.1%, 95%CI 67.1-76.7) followed by high TG (20.2%, 95%CI: 16.3-24.9), high TC (12.0%, 95%CI: 9.0-15.9) and high LDL (6.5%, 95%CI: 4.3-9.6). Female sex (aPR:1.55, 95%CI: 1.32-1.84, p < 0.001) and previous use of protease inhibitor (PI) based ART regimen (aPR:1.26, 95%CI: 1.04-1.53, p = 0.018) were significantly associated with dyslipidemia. CONCLUSION: We demonstrate that the prevalence of dyslipidemia is very high as it was present in more than three quarters of the study participants. Female sex and previous use of PI based ART regimen were significantly associated with dyslipidemia. Management of dyslipidemia should be integrated in the HIV treatment package and we recommend further inquiry into the temporal relationship between dyslipidemia and DTG among ART patients, if any.

A decade of antiretroviral therapy in Uganda: what are the emerging causes of death?

BACKGROUND: The roll out of antiretroviral therapy (ART) in Sub-Saharan Africa led to a decrease in mortality. Few studies have documented the causes of deaths among patients on long term antiretroviral therapy in Sub-Saharan Africa. Our objective was to describe the causes of death among patients on long term ART in Sub-Saharan Africa. METHODS: We used data from a prospective cohort of ART naïve patients receiving care and treatment at the Infectious Diseases Institute in Kampala, Uganda. Patients were followed up for 10 years. All deaths were recorded and possible causes established using verbal autopsy. Deaths were grouped as HIV-related (ART toxicities, any opportunistic infections (OIs) and HIV-related malignancies) and non-HIV related deaths while some remained unknown. We used Kaplan Meier survival methods to estimate cumulative incidence and rates of mortality for all causes of death. RESULTS: Of the 559, (386, 69%) were female, median age 36 years (IQR: 21-44), 89% had WHO clinical stages 3 and 4, and median CD4 count at ART initiation was 98 cells/µL (IQR: 21-163). A total of 127 (22.7%) deaths occurred in 10 years. The HIV related causes of death (n = 70) included the following; Tuberculosis 17 (24.3%), Cryptococcal meningitis 10 (15.7%), Kaposi's Sarcoma 7(10%), HIV related toxicity 6 (8.6%), HIV related anemia 5(7.1%), Pneumocystis carinii Pneumonia (PCP) 5 (7.1%), HIV related chronic diarrhea 4 (5.7%), Non-Hodgkin Lymphoma 3 (4.3%), Herpes Zoster 2 (2.8%), other 10 (14.3%). The non-HIV related causes of death (n = 20) included non-communicable diseases (diabetes, hypertension, stroke) 6 (30%), malaria 3 (15%), pregnancy-related death 2 (10%), cervical cancer 2 (10%), trauma 1(5%) and others 6 (30%). CONCLUSION: Despite the higher rates of deaths from OIs in the early years of ART initiation, we observed an emergence of non-HIV related causes of morbidity and mortality. It is recommended that HIV programs in resource-limited settings start planning for screening and treatment of non-communicable diseases.

Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.

OBJECTIVE: T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery. METHODS: A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/µl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry. RESULTS: Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. CONCLUSION: Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa.

Significant rates of risky sexual behaviours among HIV-infected patients failing first-line ART: A sub-study of the Europe-Africa Research Network for the Evaluation of Second-line Therapy trial.

There are limited data on the prevalence of risky sexual behaviours in individuals failing first-line antiretroviral therapy (ART) and changes in sexual behaviour after switch to second-line ART. We undertook a sexual behaviour sub-study of Ugandan adults enrolled in the Europe-Africa Research Network for the Evaluation of Second-line Therapy trial. A standardized questionnaire was used to collect sexual behaviour data and, in particular, risky sexual behaviours (defined as additional sexual partners to main sexual partner, inconsistent use of condoms, non-disclosure to sexual partners, and exchange of money for sex). Of the 79 participants enrolled in the sub-study, 62% were female, median age (IQR) was 37 (32-42) years, median CD4 cell count (IQR) was 79 (50-153) cells/µl, and median HIV viral load log was 4.9 copies/ml (IQR: 4.5-5.3) at enrolment. The majority were in long-term stable relationships; 69.6% had a main sexual partner and 87.3% of these had been sexually active in the preceding six months. At enrolment, around 20% reported other sexual partners, but this was higher among men than women (36% versus 6.7 %, p < 0.001). In 50% there was inconsistent condom use with their main sexual partner and a similar proportion with other sexual partners, both at baseline and follow-up. Forty-three per cent of participants had not disclosed their HIV status to their main sexual partner (73% with other sexual partners) at enrolment, which was similar in men and women. Overall, there was no significant change in these sexual behaviours over the 96 weeks following switch to second-line ART, but rate of non-disclosure of HIV status declined significantly (43.6% versus 19.6%, p <0.05). Among persons failing first-line ART, risky sexual behaviours were prevalent, which has implications for potential onward transmission of drug-resistant virus. There is need to intensify sexual risk reduction counselling and promotion of partner testing and disclosure, especially at diagnosis of treatment failure and following switch to second- or third-line ART.

The medical management of central nervous system infections in Uganda and the potential impact of an algorithm-based approach to improve outcomes.

BACKGROUND: In sub-Saharan Africa, HIV has increased the spectrum of central nervous system (CNS) infections. The etiological diagnosis is often difficult. Mortality from CNS infections is higher in sub-Saharan Africa compared to Western countries. This study examines the medical management of CNS infections in Uganda. We also propose a clinical algorithm to manage CNS infections in an effective, systematic, and resource-efficient manner. METHODS: We prospectively followed 100 consecutive adult patients who were admitted to Mulago Hospital with a suspected diagnosis of a CNS infection without any active participation in their management. From the clinical and outcome data, we created an algorithm to manage CNS infections, which was appropriate for this resource-limited, high HIV prevalence setting. RESULTS: Only 32 patients had a laboratory confirmed diagnosis and 23 of these were diagnosed with cryptococcal meningitis. Overall mortality was 39%, and mortality trended upward when the diagnosis was delayed past 3 days. The initial diagnoses were made clinically without significant laboratory data in 92 of the 100 patients. Because HIV positive patients have a unique spectrum of CNS infections, we created an algorithm that identified HIV-positive patients and diagnosed those with cryptococcal meningitis. After cryptococcal infection was ruled out, previously published algorithms were used to assist in the early diagnosis and treatment of bacterial meningitis, tuberculous meningitis, and other common central nervous system infections. In retrospective comparison with current management, the CNS algorithm reduced overall time to diagnosis and initiate treatment of cryptococcal meningitis from 3.5 days to less than 1 day. CONCLUSIONS: CNS infections are complex and difficult to diagnose and treat in Uganda, and are associated with high in-hospital mortality. A clinical algorithm may significantly decrease the time to diagnose and treat CNS infections in a resource-limited setting.

Hazardous alcohol consumption is not associated with CD4+ T-cell count decline among PLHIV in Kampala Uganda: A prospective cohort study.

INTRODUCTION: There is limited data on the effects of alcohol on immunological response among persons living with HIV (PLHIV) in sub-Saharan Africa. We assessed the relationship between hazardous alcohol use and CD4+ T-cell count, among PLHIV in Uganda. METHODS: PLHIV aged ≥ 18 years were enrolled in a cohort study at the Infectious diseases clinic Kampala, Uganda. Alcohol consumption was assessed at enrolment (baseline) and 6 monthly thereafter using the alcohol use disorders identification test (AUDIT). The CD4+ T-cell counts, assessed at baseline and over the next 12 months were compared between alcohol use strata, using linear mixed effects regression. Using longitudinal mediation analysis methods, we estimated the effect of alcohol induced ART non-adherence on CD4+ T-cell count. RESULTS: Of the 1566 participants enrolled, 863(44.1%) were non-alcohol users (AUDIT score = 0), 433(27.7%) were non-hazardous (AUDIT score 1-7) alcohol users while 270 (17.2%) were hazardous (AUDIT score ≥ 8) alcohol users. The overall median (IQR) baseline CD4+ T-cell count was 356 (243-516) cells/µl. There were no differences in the median baseline CD4+ T-cell count between hazardous and non-hazardous alcohol users compared to non-alcohol users in both the non-ART (p = 0.43) and ART group (p = 0.77). The mean CD4+ T-cell count over 12 months was not different between hazardous alcohol users and non-alcohol users (non-ART group p = 0.88 and ART group p = 0.62), nor between non-hazardous alcohol users and non-alcohol users (and non-ART group p = 0.66 and ART group p = 0.20). Alcohol use was not associated with a significant natural direct effect on CD4+ T-cell count (1.37 95%CI [-1.78, 4.52] cells/µl, p = 0.39) but had a statistically significant natural indirect effect on reduction of CD4+ T-cell count (-0.91 cells/µl [-1.36, -0.45], p < 0.001) mediated through ART non-adherence. CONCLUSION: Hazardous alcohol use among PLHIV was not directly associated with lower CD4+ T-cell count but had a significant natural indirect effect on CD4+ T-cell count mediated through ART non-adherence. Among PLHIV with lower than expected CD4+ T-cell count, alcohol consumption should be excluded as an underlying factor for non-adherence to ART and any interventions targeting alcohol use should tackle possible ART non-adherence.

Bilateral pedal edema in an HIV patient: Lopinavir/Ritonavir-containing treatment regimen as a potential cause?

A large number of patients are switched to second-line antiretroviral therapy, especially in resource limited settings. Lopinavir/Ritonavir is the main drug used in second-line treatment regimens. We describe a patient attending an HIV treatment centre in Kampala, Uganda, who presented with bilateral non-tender pitting inflammatory edema two weeks after switching to a Lopinavir/Ritonavir-containing second-line treatment regimen. The lack of an alternate explanation led us to suspect that Lopinavir/Ritonavir was potentially responsible for the edema.