Modelling trends of CD4 counts for patients on antiretroviral therapy (ART): a comprehensive health care clinic in Nairobi, Kenya

Background In resource-limited settings, changes in CD4 counts constitute an important component in patient monitoring and evaluation of treatment response as these patients do not have access to routine viral load testing. In this study, we quantified trends on CD4 counts in patients on highly active antiretroviral therapy (HAART) in a comprehensive health care clinic in Kenya between 2011 and 2017. We evaluated the rate of change in CD4 cell count in response to antiretroviral treatment. We further assessed factors that influenced time to treatment change focusing on baseline characteristics of the patients and different initial drug regimens used. This was a retrospective study involving 432 naïve HIV patients that had at least two CD4 count measurements for the period. The relationship between CD4 cell count and time was modeled using a semi parametric mixed effects model while the Cox proportional hazards model was used to assess factors associated with the first regimen change. Results Majority of the patients were females and the average CD4 count at start of treatment was 362.1 $$cell/mm^3$$ c e l l / m m 3 . The CD4 count measurements increased nonlinearly over time and these trends were similar regardless of the treatment regimen administered to the patients. The change of logarithm CD4 cell count rises fast for in the first 450 days of antiretroviral initiation. The average time to first regimen change was 2142 days. Tenoforvir (TDF) based regimens had a lower drug substitution(aHR 0.2682, 95% CI:0.08263- 0.8706) compared to Zidovudine(AZT). Conclusion The backbone used was found to be associated with regimen changes among the patients with fewer switches being observed, with the use of TDF when compared to AZT. There was however no significant difference between TDF and AZT in terms of the rate of change in logarithm CD4 count over time.

A double-blind, randomized controlled trial to examine the effect of Moringa oleifera leaf powder supplementation on the immune status and anthropometric parameters of adult HIV patients on antiretroviral therapy in a resource-limited setting

Background People living with HIV (PLHIV) in resource-limited settings are vulnerable to malnutrition. Nutritional interventions aimed at improving food insecurity and malnutrition, together with antiretroviral therapy (ART), could improve treatment outcomes. In Nigeria, there is a high awareness of the nutraceutical benefits of Moringa oleifera. Thus, this study aimed to evaluate the effects of Moringa oleifera leaf supplementation on the CD4 counts, viral load and anthropometric of HIV-positive adults on ART. Methods This was a double-blind, randomized study. Two hundred HIV-positive patients were randomly allocated to either the Moringa Oleifera group (MOG) given Moringa oleifera leaf powder or the control group (COG) given a placebo. Changes in anthropometric parameters [weight; body mass index (BMI)] and CD4 cell counts were measured monthly for six months, while HIV-1 viral loads were measured at baseline and the end of the study for both groups. Results Over the study period, the treatment by time interaction shows a significant difference in CD4 counts by treatment group (p<0.0001). A further estimate of fixed effects showed that the CD4 counts among MOG were 10.33 folds greater than COG over the study period. However, the viral load (p = 0.9558) and all the anthropometric parameters (weight; p = 0.5556 and BMI; p = 0.5145) between the two groups were not significantly different over time. All tests were conducted at 95CI. Conclusion This study revealed that Moringa oleifera leaf supplementation was associated with increased CD4 cell counts of PLHIV on ART in a resource-limited setting. Programs in low-resource settings, such as Nigeria, should consider nutritional supplementation as part of a comprehensive approach to ensure optimal treatment outcomes in PLHIV.

Effects of Aerobic Exercise on Depression and CD4 Counts in People Living with HIV

Introduction: HIV patients often experience psychological and physical disorders which greatly affect the adherence of people living with HIV/AIDS (PLWHA). This study aimed to assess the effects of aerobic exercise on the levels of depression and CD4 cell count of HIV patients.Methods: This study used a pre-post quasi-experimental design with a control group. The sampling technique was consecutive sampling, with a total sample of 52 HIV respondents. Depression level was measured using the Beck Depression Inventory (BDI), while CD4 count was measured using the Pyma analyser. The aerobic exercise intervention was given three times a week with a duration of 20-30 minutes each for four weeks. The collected data were analysed using a paired sample t-test and an independent sample t-test.Results: The results showed a significant difference in the mean value of depression before and after the intervention of aerobic exercise (M =25.15 and M=22.46, respectively) with p = 0.001. Similarly, there was a significant difference in the mean of CD4 counts between the control group (M=303.38) and the intervention group (M=305.38) after the intervention with p = 0.031.Conclusion: Aerobic exercise is effective in reducing depression levels and increasing CD4 counts in HIV patients. Immune system cells circulate more rapidly and there is a boost in the production of macrophages, cells that can attack bacteria.

Outcome of Fixed Dose Combination of Tenofovir, Lamivudine and Dolutegravir in Rural HIV Care Facility in Nigeria

Background: Antiretroviral therapy (ART) has significantly increased the lifespan of people living with HIV. Currently, fixed dosed combination therapy (Tenofovir, Lamivudine, and Dolutegravir) is being introduced in most countries in the Sub- Saharan Africa. There is need for a clinical and immunological assessment of HIV patients transitioned to this new therapy over a period of 2 years. Objectives: To determine the proportion of patients whose viral load was suppressed to <20 copies/ml following two years therapy with Dolutegravir-based fixed-dose combination therapy. Methods: This retrospective cohort study was carried out in a Comprehensive Healthcare Centre (CHC), a facility affiliated with Nnamdi Azikiwe University Teaching Hospital Nigeria. The primary outcome measure was the proportion of patients whose viral load was suppressed to <20 copies/ml. The plasma viral load (HIV-RNA) assay was done using real time PCR and CD4+ T- lymphocyte (CD4+) counts were estimated using Flow Cytometry. The exclusion criteria were patients who has invalid data base and patients with comorbidities associated with HIV. Results: A total of 537 HIV1 sero-positive patients were enrolled for ART care over a period of 2 years (2017-2018). Females in the age group (41-50 years) constituted the bulk (36.9%) of the patients whilst the least (5.3%) were males in the age group (8 to 30 years). The mean CD4 count of patients was 847.35cells/mm3. More females (45.9%) had CD4+counts over 500cells/mm3 whilst the percentage of males with CD4+ cell counts over 500cells/mm3 was 43.8%. Majority, 405 constituting 75.4% of the patients have suppressed viral load (<20 copies/ml) signifying that the centre is achieving success with respect to service delivery and ART. Patients with unsuppressed viral loads were more among Females with CD4+ counts in the range of 200-499 cells/mm3and this may be as a result of other associated factors which will be elucidated in future studies. Conclusion: Dolutegravir-based fixed-dose combination therapy suppressed viral load to <20 copies/ml in more than 75% of patients receiving the therapy. Enhanced adherence and effective doctor-patient relationship could be associated with the viral suppression observed in this study. Key words: Immunology, virology, HIV Outcome, Dolutegravir-based combination therapy, anti retroviral therapy.

Cost-effectiveness of cryptococcal antigen screening at CD4 counts of 101–200 cells/µL in Botswana

Background: Cryptococcal antigen (CrAg) screening in individuals with advanced HIV reduces cryptococcal meningitis (CM) cases and deaths. The World Health Organization recently recommended increasing screening thresholds from CD4 ≤100 cells/µL to ≤200 cells/µL. CrAg screening at CD4 ≤100 cells/µL is cost-effective; however, the cost-effectiveness of screening patients with CD4 101–200 cells/µL requires evaluation. Methods: Using a decision analytic model with Botswana-specific cost and clinical estimates, we evaluated CrAg screening and treatment among individuals with CD4 counts of 101–200 cells/µL. We estimated the number of CM cases and deaths nationally and treatment costs without screening. For screening we modeled the number of CrAg tests performed, number of CrAg-positive patients identified, proportion started on pre-emptive fluconazole, CM cases and deaths. Screening and treatment costs were estimated and cost per death averted or disability-adjusted life year (DALY) saved compared with no screening. Results: Without screening, we estimated 142 CM cases and 85 deaths annually among individuals with CD4 101–200 cells/µL, with treatment costs of $368,982. With CrAg screening, an estimated 33,036 CrAg tests are performed, and 48 deaths avoided (1,017 DALYs saved). While CrAg screening costs an additional $155,601, overall treatment costs fall by $39,600 (preemptive and hospital-based CM treatment), yielding a net increase of $116,001. Compared to no screening, high coverage of CrAg screening and pre-emptive treatment for CrAg-positive individuals in this population avoids one death for $2440 and $114 per DALY saved. In sensitivity analyses assuming a higher proportion of antiretroviral therapy (ART)-naïve patients (75% versus 15%), cost per death averted was $1472; $69 per DALY saved. Conclusions: CrAg screening for individuals with CD4 101–200 cells/µL was estimated to have a modest impact, involve additional costs, and be less cost-effective than screening populations with CD4 counts ≤100 cells/µL. Additional CrAg screening costs must be considered against other health system priorities.

The Underrated Salivary Virome of Men Who Have Sex With Men Infected With HIV

Salivary virome is important for oral ecosystem, but there are few reports on people living with HIV. We performed metagenomic sequencing to compare composition and functional genes of salivary virobiota between one HIV-negative and four HIV-positive groups in which participants were all men who have sex with men (MSM) with different immunosuppression statuses (five samples per group) to find the evidence that salivary virobiota plays a role in the pathogenesis of oral disease. Acute-stage subjects achieved a positive result of HIV RNA, but HIV antibody negative or indeterminate, whereas individuals with mild, moderate, and severe immunosuppression exhibited CD4+ T-lymphocyte counts of at least 500, 200–499, and less than 200 cells/μL or opportunistic infection, respectively. The results showed the composition of salivary virus genera in subjects with mild immunosuppression was the most similar to that in healthy people, followed by that in the acute stage; under severe immunosuppression, virus genera were suppressed and more similar to that under moderate immunosuppression. Furthermore, abnormally high abundance of Lymphocryptovirus was particularly obvious in MSM with HIV infection. Analysis of KEGG Pathway revealed that Caulobacter cell cycle, which affects cell duplication, became shorter in HIV-positive subjects. It is worth noting that in acute-stage participants, protein digestion and absorption related to the anti-HIV-1 activity of secretory leukocyte protease inhibitor was increased. Moreover, in the severely immunosuppressed subjects, glutathione metabolism, which is associated with the activation of lymphocytes, was enhanced. Nevertheless, the ecological dysbiosis in HIV-positive salivary virobiota possibly depended on the changes in blood viral load, and salivary dysfunction of MSM infected with HIV may be related to CD4 counts. Ribonucleoside diphosphate reductase subunit M1 in purine metabolism was negatively correlated, though weakly, to CD4 counts, which may be related to the promotion of HIV-1 DNA synthesis in peripheral blood lymphocytes. 7-Cyano-7-deazaguanine synthase in folate biosynthesis was weakly positively correlated with HIV viral load, suggesting that this compound was produced excessively to correct oral dysfunction for maintaining normal cell development. Despite the limited number of samples, the present study provided insight into the potential role of salivary virome in the oral function of HIV infected MSM.

A retrospective study of distribution of HIV associated malignancies among inpatients from 2007 to 2020 in China

HIV-associated malignancies are responsible for morbidity and mortality increasingly in the era of potent antiretroviral therapy. This study aimed to investigate the distribution of HIV-associated malignancies among inpatients, the immunodeficiency and the effect of antiretroviral therapy (ART) on spectrum of HIV-associated malignancies. A total of 438 cases were enrolled from 2007 to 2020 in Beijing Ditan Hospital. Demographic, clinical and laboratory data, managements, and outcomes were collected and analyzed retrospectively. Of 438 cases, 433 were assigned to non-AIDS-defining cancers (NADCs) (n = 200, 45.7%) and AIDS-defining cancers (ADCs) (n = 233, 53.2%), 5 (1.1%) with lymphoma were not specified further. No significant change was observed in the proportion of NADCs and ADCs as time goes on. Of NADCs, lung cancer (n = 38, 19%) was the most common type, followed by thyroid cancer (n = 17, 8.5%). Patients with ADCs had lower CD4 counts(104.5/μL vs. 314/μL), less suppression of HIVRNA(OR 0.23, 95%CI 0.16–0.35) compared to those with NADCs. ART did not affect spectrum of NADCs, but affect that of ADCs (between patients with detectable and undetectable HIVRNA). ADCs remain frequent in China, and NADCs play an important role in morbidity and mortality of HIV positive population.

Cavitary Legionella Pneumonia in AIDS: When Intracellular Immunity Failure Leads to Rapid Intrapulmonary Cavitation

Introduction. Legionella is a frequent cause of bacterial pneumonia in patients with AIDS. While multiple organisms have been associated with cavitary pneumonia in this population, Legionella has not. Clinical Case. A middle-aged woman with HIV-AIDS and severely depressed CD-4 count presented with one month of progressively worsening productive cough and dyspnea. Serial imaging showed focal consolidations which multiplied and cavitated over the subsequent days. Legionella urine antigen was positive, and appropriate treatment was continued for 3 weeks total. The patient recovered quickly, and follow-up imaging 8 weeks later showed near-resolution of all lesions. Discussion. Cavitary pneumonia secondary to Legionella has been seldom described, traditionally in the context of immunosuppressive therapy. Patients with AIDS and severely depressed CD4 counts have significantly compromised cell-mediated immunity. This case highlights the importance of consideration for legionellosis in rapidly progressing cavitary pneumonia, especially in patients with severely compromised cell-mediated immunity, including those with HIV-AIDS.

A Lower CD4 Count Predicts Most Causes of Death except Cardiovascular Deaths. The Austrian HIV Cohort Study

(1) Objective: To investigate changes in mortality rates and predictors of all-cause mortality as well as specific causes of death over time among HIV-positive individuals in the combination antiretroviral therapy (cART) era. (2) Methods: We analyzed all-cause as well as cause-specific mortality among the Austrian HIV Cohort Study between 1997 and 2014. Observation time was divided into five periods: Period 1: 1997–2000; period 2: 2001–2004; period 3: 2005–2008; period 4: 2009–2011; and period 5: 2012–2014. Mortality rates are presented as deaths per 100 person-years (d/100py). Potential risk factors associated with all-cause mortality and specific causes of death were identified by using multivariable Cox proportional hazard models. Models were adjusted for time-updated CD4, age and cART, HIV transmission category, population size of residence area and country of birth. To assess potential nonlinear associations, we fitted all CD4 counts per patient using restricted cubic splines with truncation at 1000 cells/mm3. Vital status of patients was cross-checked with death registry data. (3) Results: Of 6848 patients (59,704 person-years of observation), 1192 died: 380 (31.9%) from AIDS-related diseases. All-cause mortality rates decreased continuously from 3.49 d/100py in period 1 to 1.40 d/100py in period 5. Death due to AIDS-related diseases, liver-related diseases and non-AIDS infections declined, whereas cardiovascular diseases as cause of death remained stable (0.27 d/100py in period 1, 0.10 d/100py in period 2, 0.16 d/100py in period 3, 0.09 d/100py in period 4 and 0.14 d/100py in period 5) and deaths due to non-AIDS-defining malignancies increased. Compared to latest CD4 counts of 500 cells/mm3, lower CD4 counts conferred a higher risk of deaths due to AIDS-related diseases, liver-related diseases, non-AIDS infections and non-AIDS-defining malignancies, whereas no significant association was observed for cardiovascular mortality. Results were similar in sensitivity analyses where observation time was divided into two periods: 1997–2004 and 2005–2014. (4) Conclusion: Since the introduction of cART, risk of death decreased and causes of death changed. We do not find evidence that HIV-positive individuals with a low CD4 count are more likely to die from cardiovascular diseases.