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Implementation of WHO guidelines on management of advanced HIV disease and its impact among TB co-infected patients in Tanzania: a retrospective follow-up study.
BACKGROUND: The commonest causes of mortality in people living with HIV (PLHIV) are preventable and the majority can be attributed to undiagnosed tuberculosis (TB). National HIV/AIDS control programs are encouraged to implement the WHO package of interventions to improve survival among PLHIV. We assessed the implementation of the WHO TB-related package of care for Advanced HIV Disease (AHD) and its impact on treatment outcomes among HIV/TB patients in Tanzania. METHODS: A retrospective cohort study was employed among HIV/AIDS patients on antiretroviral therapy from 21 public health facilities in three regions (Dar es Salaam, Coastal, and Morogoro) of Tanzania. Patients enrolled in care between January 2013- June 2017 (before the introduction of the WHO guidelines) and July 2017-Sept 2018 (during the implementation of the guidelines) were recruited. Data abstraction was done from patient hospital files using a structured questionnaire uploaded on a tablet. RESULTS: Data from 2624 patients records were collected. Overall, 50% of patients with HIV had AHD with 7.8% of these co-infected with TB. Among AHD participants, 58.3% were female, 80.7% were from urban areas and 40.0% visited care and treatment centres as self-referrals. Implementation of the WHO AHD package of care was very low, ranging from 0% for Urine LF-LAM test done among patients with symptoms and signs of TB to 39.7% AHD concurrent with TB patients whose ART initiation was deferred for 2 weeks. Overall, the Proportion of AHD patients diagnosed with TB was 4.8%, Of which sputum Xpert as the first test for TB diagnosis was 4.4%. Five patients (0.6%) were documented to have received IPT at enrolment. Tailored counselling to ensure optimal adherence to ART for viral suppression was given to 12.1%. AHD patients co-infected with TB were retained in care more before the introduction of WHO AHD guideline (82.1%) compared to the period after the introduction of the guideline (53.9%) (p = 0.008). Clinical failure at 6 months among AHD patients was 10.6% before the guideline and 11.4% after the guideline. Immunological failure was observed in 1 patient (9.1%) before the guideline and 1 patient (7.1%) after the guideline. After the introduction of the guideline, mortality was 5.9% and no mortality was observed before the guideline. All the differences were not statistically significant. CONCLUSIONS: Implementation of the TB related WHO packages of care for AHD is very low. Except for TB diagnosis, other parameters did not improve with the introduction of the guidelines. More research is recommended to ascertain the effectiveness of guidelines as well as an understanding of the mechanisms involved.
The burden and determinants of self-reported non-communicable disease comorbidities among HIV positive adults in Tanzania: Insights from the Tanzania HIV Impact Survey 2022-2023
Altered Lipid Profiles and Vaccine Induced-Humoral Responses in Children Living With HIV on Antiretroviral Therapy in Tanzania.
People living with HIV, even under therapy, have a high burden of age-related co-morbidities including an increased risk of dyslipidemia (which often predisposes to cardiovascular diseases) and immune-aging. In this study, lipid profiles and antibody responses to measles and pertussis toxin vaccines were compared between ART experienced HIV+ children (n=64) aged 5-10 years, and their age- and sex-matched HIV- controls (n=47). Prevalence of high-density lipoprotein cholesterol (HDL-c) and triglyceride-driven dyslipidemia was higher among treated HIV+ children than in controls (51.6% vs 27.7% respectively, p < 0.019). In a multivariate Poisson regression model adjusted for age, sex and BMI, the association between low HDL-c, hypertriglyceridemia and HIV remained significantly high (for HDL-c: ARR: 0.89, 95% CI: 0.82 - 0.96, p = 0.003; for triglycerides: ARR: 1.54, 95% CI: 1.31 - 1.81, p < 0.001). Among HIV+ children, the use of lopinavir/ritonavir, a protease-based antiretroviral therapy was also associated elevation of triglyceride levels (p = 0.032). Also, HIV+ children had a 2.8-fold reduction of anti-measles IgG titers and 17.1-fold reduction of anti-pertussis toxin IgG levels when compared to HIV- children. Our findings suggest that dyslipidemia and inadequate vaccine-induced antibody responses observed in this population of young African HIV+ children might increase their risk for premature onset of cardiovascular illnesses and acquisition of preventable diseases.
Depletion of Human Papilloma Virus E6- and E7-Oncoprotein-Specific T-Cell Responses in Women Living With HIV.
BACKGROUND: Cervical cancer - caused by persistent High Risk Human Papilloma Virus (HR HPV) infections - is the second most common cancer affecting women globally. HIV infection increases the risk for HPV persistence, associated disease progression and malignant cell transformation. We therefore hypothesized that this risk increase is directly linked to HIV infection associated dysfunction or depletion of HPV-oncoprotein-specific T-cell responses. METHODS: The 2H study specifically included HIV+ and HIV- women with and without cervical lesions and cancer to analyze HPV oncogene-specific T cell responses in relation to HPV infection, cervical lesion status and HIV status. Oncoprotein E6 and E7 specific T-cell responses were quantified for the most relevant types HPV16, 18 and 45 and control antigens (CMV-pp65) and -PPD in 373 women, using fresh peripheral blood mononuclear cells in an IFN-γ release ELISpot assay. RESULTS: Overall, systemic E6- and E7-oncoprotein-specific T-cell responses were infrequent and of low magnitude, when compared to CMV-pp65 and -PPD (p < 0.001 for all HR HPV types). Within HIV negative women infected with either HPV16, 18 or 45, HPV16 infected women had lowest frequency of autologous-type-E6/E7-specific T-cell responses (33%, 16/49), as compared to HPV18 (46% (6/13), p = 0.516) and HPV45 (69% (9/13), p = 0.026) infected women. Prevalent HPV18 and 45, but not HPV16 infections were linked to detectable oncoprotein-specific T-cell responses, and for these infections, HIV infection significantly diminished T-cell responses targeting the autologous infecting genotype. Within women living with HIV, low CD4 T-cell counts, detectable HIV viremia as well as cancerous and precancerous lesions were significantly associated with depletion of HPV oncoprotein-specific T-cell responses. DISCUSSION: Depletion of HPV-oncoprotein-specific T-cell responses likely contributes to the increased risk for HR HPV persistence and associated cancerogenesis in women living with HIV. The low inherent immunogenicity of HPV16 oncoproteins may contribute to the exceptional potential for cancerogenesis associated with HPV16 infections.
Long-term follow-up on HIV infected and non-infected women with cervical cancer from Tanzania: staging, access to cancer-directed therapies and associated survival in a real-life remote setting
Implementation of WHO guidelines on management of advanced HIV disease and its impact among TB co-infected patients in Tanzania: a retrospective follow-up study
Abstract Background: The commonest causes of mortality in people living with HIV (PLHIV) are preventable and the majority can be attributed to undiagnosed tuberculosis (TB). National HIV/AIDS control programs are encouraged to implement the WHO package of interventions to improve survival among PLHIV. We assessed the implementation of the WHO TB-related package of care for Advanced HIV Disease (AHD) and its impact on treatment outcomes among HIV/TB patients in Tanzania. Methods: A retrospective cohort study was employed among HIV/AIDS patients on antiretroviral therapy from 21 public health facilities in three regions (Dar es Salaam, Coastal, and Morogoro) of Tanzania. Patients enrolled in care between January 2013- June 2017 (before the introduction of the WHO guidelines) and July 2017-Sept 2018 (during the implementation of the guidelines) were recruited. Data abstraction was done from patient hospital files using a structured questionnaire uploaded on a tablet. Results: Data from 2624 patients records were collected. Overall, 50% of patients with HIV had AHD with 7.8% of these co-infected with TB. Among AHD participants, 58.3% were female, 80.7% were from urban areas and 40.0% visited care and treatment centres as self-referrals. Implementation of the WHO AHD package of care was very low, ranging from 0% for Urine LF-LAM test done among patients with symptoms and signs of TB to 39.7% AHD concurrent with TB patients whose ART initiation was deferred for 2 weeks. Overall, the Proportion of AHD patients diagnosed with TB was 4.8%, Of which sputum Xpert as the first test for TB diagnosis was 4.4%. Five patients (0.6%) were documented to have received IPT at enrolment. Tailored counselling to ensure optimal adherence to ART for viral suppression was given to 12.1%. AHD patients co-infected with TB were retained in care more before the introduction of WHO AHD guideline (82.1%) compared to the period after the introduction of the guideline (53.9%) (p = 0.008). Clinical failure at 6 months among AHD patients was 10.6% before the guideline and 11.4% after the guideline. Immunological failure was observed in 1 patient (9.1%) before the guideline and 1 patient (7.1%) after the guideline. After the introduction of the guideline, mortality was 5.9% and no mortality was observed before the guideline. All the differences were not statistically significant. Conclusions: Implementation of the TB related WHO packages of care for AHD is very low. Except for TB diagnosis, other parameters did not improve with the introduction of the guidelines. More research is recommended to ascertain the effectiveness of guidelines as well as an understanding of the mechanisms involved. Keywords: AHD; AHD guideline; HIV; TB; WHO.