Dataset Information

Morbidity and mortality according to latest CD4+ cell count among HIV positive individuals in South Africa who enrolled in project Phidisa.

ABSTRACT:

Background

Short-term morbidity and mortality rates for HIV positive soldiers in the South African National Defence Force (SANDF) would inform decisions about deployment and HIV disease management. Risks were determined according to the latest CD4+ cell count and use of antiretroviral therapy (ART) for HIV positive individuals in the SANDF and their dependents.

Methods and findings

A total of 7,114 participants were enrolled and followed for mortality over a median of 4.7 years (IQR: 1.9, 7.1 years). For a planned subset (5,976), progression of disease (POD) and grade 4, potentially life-threatening events were also ascertained. CD4+ count and viral load were measured every 3 to 6 months. Poisson regression was used to compare event rates by latest CD4+ count (<50, 50-99, 100-199, 200-349, 350-499, 500+) with a focus on upper three strata, and to estimate relative risks (RRs) (ART/no ART). Median entry CD4+ was 207 cells/mm3. During follow-up over 70% were prescribed ART. Over follow-up 1,226 participants died; rates ranged from 57.6 (< 50 cells) to 0.8 (500+ cells) per 100 person years (py). Compared to those with latest CD4+ 200-349 (2.2/100 py), death rates were significantly lower (p<0.001), as expected, for those with 350-499 (0.9/100 py) and with 500+ cells (0.8/100 py). The composite outcome of death, POD or grade 4 events occurred in 2,302 participants (4,045 events); rates were similar in higher CD4+ count strata (9.4 for 350-499 and 7.9 for 500+ cells) and lower than those with counts 200-349 cells (13.5) (p<0.001). For those with latest CD4+ 350+ cells, 63% of the composite outcomes (680 of 1,074) were grade 4 events.

Conclusion

Rates of morbidity and mortality are lowest among those with CD4+ count of 350 or higher and rates do not differ for those with counts of 350-499 versus 500+ cells. Grade 4 events are the predominant morbidity for participants with CD4+ counts of 350+ cells.

SUBMITTER: Maduna PH

PROVIDER: S-EPMC4391777 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Morbidity and mortality according to latest CD4+ cell count among HIV positive individuals in South Africa who enrolled in project Phidisa.

Maduna Patrick H PH Dolan Matt M Kondlo Lwando L Mabuza Honey H Dlamini Judith N JN Polis Mike M Mnisi Thabo T Orsega Susan S Maja Patrick P Ledwaba Lotty L Molefe Thuthukile T Sangweni Phumelele P Malan Lisette L Matchaba Gugu G Khabo Paul P Grandits Greg G Neaton James D JD

PloS one 20150409 4

<h4>Background</h4>Short-term morbidity and mortality rates for HIV positive soldiers in the South African National Defence Force (SANDF) would inform decisions about deployment and HIV disease management. Risks were determined according to the latest CD4+ cell count and use of antiretroviral therapy (ART) for HIV positive individuals in the SANDF and their dependents.<h4>Methods and findings</h4>A total of 7,114 participants were enrolled and followed for mortality over a median of 4.7 years (I ...[more]

PMID: 25856495

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Project description:BackgroundWe describe CD4 count recovery among HIV positive individuals who initiated antiretroviral therapy (ART) with and without severe immune suppression using complete laboratory data from South Africa's national HIV treatment programme between 2010 and 2014 and discuss implications for CD4 count monitoring.MethodsRetrospective analysis of routinely collected laboratory data from South Africa's National Health Laboratory Service (NHLS). A probabilistic record linkage algorithm was used to create a cohort of HIV positive individuals who initiated ART between 2010 and 2014 based on timing of CD4 count and viral load measurements. A CD4 count < 50 copies/μl at ART initiation was considered severe immunosuppression. A multivariable piecewise mixed-effects linear regression model adjusting for age, gender, year of starting ART, viral suppression in follow up and province was used to predict CD4 counts during follow up.Results1,070,900 individuals had evidence of starting ART during 2010-2014 and met the criteria for inclusion in the cohort -46.6% starting ART with CD4 < 200 cells/μl and 10.1% with CD4 < 50 cells/ μl. For individuals with CD4 counts < 200 cells/μl, predicted CD4 counts > 200 cells/μl, >350 cells/μl and >500 cells/μl corresponded with mean follow up durations of 1.5 years (standard deviation [s.d] 1.1), 1.9years (s.d 1.2) and 2.1 years (s.d 1.3 years). For those with CD4 counts < 50 cells/μl, predicted CD4 count above these threshold corresponded with mean follow up durations of 2.5 years (s.d 0.9 years), 4.4 years (s.d 0.4 years) and 5.0 years (s.d 0.1years) for recovery to the same thresholds. CD4 count recovery varied mostly with duration on ART, CD4 count at the start of ART and gender.ConclusionFor individuals starting with ART with severe immunosuppression, CD4 recovery to 200cells/μl did not occur or took longer than 12 month for significant proportions. CD4 monitoring and interventions recommended for advanced HIV disease should continue until full recovery.

Project description:BackgroundPlasma HIV-1 RNA monitoring is one of the standard tests for the management of HIV-1 infection. While HIV-1 RNA can be quantified using several commercial tests, no test has been commercialized for HIV-2 RNA quantification. We studied the relationship between plasma HIV-2 viral load (VL) and CD4 count in West African patients who were either receiving antiretroviral therapy (ART) or treatment-naïve.MethodA cross sectional survey was conducted among HIV-2-infected individuals followed in three countries in West Africa from March to December 2012. All HIV-2 infected-patients who attended one of the participating clinics were proposed a plasma HIV-2 viral load measurement. HIV-2 RNA was quantified using the new ultrasensitive in-house real-time PCR assay with a detection threshold of 10 copies/ mL (cps/mL).ResultsA total of 351 HIV-2-infected individuals participated in this study, of whom 131 (37.3%) were treatment naïve and 220 (62.7%) had initiated ART. Among treatment-naïve patients, 60 (46.5%) had undetectable plasma HIV-2 viral load (<10 cps/mL), it was detectable between 10-100 cps/mL in 35.8%, between 100-1000 cps/mL in 11.7% and >1000 cps/mL in 6.0% of the patients. Most of the treatment-naïve patients (70.2%) had CD4-T cell count ≥500 cells/mm3 and 43 (46.7%) of these patients had a detectable VL (≥10 cps/mL). Among the 220 patients receiving ART, the median CD4-T cell count rose from 231 to 393 cells/mm3 (IQR [259-561]) after a median follow-up duration of 38 months and 145 (66.0%) patients had CD4-T cell count ≤ 500 cells/mm3 with a median viral load of 10 cps/mL (IQR [10-33]). Seventy five (34.0%) patients had CD4-T cell count ≥ 500 cells/mm3, among them 14 (18.7%) had a VL between 10-100 cps/mL and 2 (2.6%) had VL >100 cps/mL.ConclusionThis study suggests that the combination of CD4-T cell count and ultrasensitive HIV-2 viral load quantification with a threshold of 10 cps/mL, could improve ART initiation among treatment naïve HIV-2-infected patients and the monitoring of ART response among patients receiving treatment.

Project description:BACKGROUND:Despite the success of prevention of mother to child transmission (PMTCT) program in South Africa, the 30% HIV prevalence among women of childbearing age requires the PMTCT program to be maximally efficient to sustain gains in the prevention of vertical HIV transmission. We aimed to determine the immunologic and virologic status at entry into antenatal care (ANC) and at childbirth among HIV positive women who conceived under the CD4<500 cells/?l antiretroviral therapy (ART) eligibility threshold and universal test and treat (UTT) policies in the Gauteng province of South Africa. METHOD:We conducted a retrospective cohort study of 692 HIV positive adult (>18 years) postpartum women who gave birth between September 2016 and December 2017. Demographic, viral load (VL) and CD4 data at ANC start (3-9 months before delivery) and delivery (3 months before/after) were obtained from medical records of consenting women. We compared CD4?500 cell/?l and viral load (VL) suppression (<400 copes/ml) rates at ANC start and delivery among women with a pre-pregnancy ART, women known HIV positive but with in-pregnancy ART and newly diagnosed women with in-pregnancy ART. Predictors of having a high CD4 and suppressed VL were assessed by log-binomial regression. RESULTS:Of the 692 participants, 394 (57.0%) had CD4 data and 326 (47.1%) had VL data. Overall women with a pre-pregnancy ART were more likely to start ANC with CD4 count?500 cell/?l (46.3% vs 24.8%, adjusted risk ratio (aRR) = 1.9; 95% confidence interval (95% CI): 1.4-2.5), compared to newly diagnosed women. This difference was no longer apparent at the time of delivery (aRR 1.2 95% CI: 0.4-3.7). Similarly, viral suppression at delivery was higher among women with pre-pregnancy ART (87.2% vs 69.3%, aRR 1.3, 95% CI: 1.1-1.6) as compared to the newly diagnosed women. Viral suppression rate among newly diagnosed women increased substantially by the time of delivery from 43.5% to 69.3% (p = 0.001). CONCLUSION:These results show that pre-pregnancy ART improves immunologic and virologic control during pregnancy and call for renewed efforts in HIV testing, linkage to ART and viral monitoring.

Project description:IntroductionPast endeavours to deal with the obstacle of expensive Cluster of Difference 4 (CD4+) count diagnostics in resource-limited settings have left a long trail of suggested continuous CD4+ count clinical covariates that turned out to be a potentially important integral part of the human immunodeficiency virus (HIV) treatment process during disease progression. However, an evaluation to determine the strongest candidates among these CD4+ count covariates has not been well documented.MethodsThe Centre for the AIDS Programme of Research in South Africa (CAPRISA) initially enrolled HIV-negative (phase 1) patients into different study cohorts. The patients who seroconverted (237) during follow-up care were enrolled again into a post-HIV infection cohort where they were further followed up with weekly to fortnightly visits up to 3 months (phase 2: acute infection), monthly visits from 3-12 months (phase 3: early infection) and quarterly visits thereafter (phase 4: established infection) until antiretroviral therapy (ART) initiation (phase 5). The CD4+ count and 46 covariates were repeatedly measured at each phase of the HIV disease progression. A multilevel partial least squares approach was applied as a variable reduction technique to determine the strongest CD4+ count covariates.ResultsOnly 18 of the 46 investigated clinical attributes were the strongest CD4+ count covariates and the top 8 were positively and independently associated with the CD4+ count. Besides the confirmatory lymphocytes, these were basophils, albumin, haematocrit, alkaline phosphatase (ALP), mean corpuscular volume (MCV), platelets, potassium and monocytes. Overall, electrolytes, proteins and red blood cells were the dominant categories for the strongest covariates.ConclusionOnly a few of the many previously suggested continuous CD4+ count clinical covariates showed the potential to become an important integral part of the treatment process. Prolonging the pre-treatment period of the HIV disease progression by effectively incorporating and managing the covariates for long-term influence on the CD4+ cell response has the potential to delay challenges associated with ART side effects.

Project description:BackgroundThe CD4 cell count signifies the health of an individual's immune system. The use of data-driven models enables clinicians to accurately interpret potential information, examine the progression of CD4 count, and deal with patient heterogeneity due to patient-specific effects. Quantile-based regression models can be used to illustrate the entire conditional distribution of an outcome and identify various covariates effects at the respective location.MethodsThis study uses the quantile mixed-effects model that assumes an asymmetric Laplace distribution for the error term. The model also incorporated multiple random effects to consider the correlation among observations. The exact maximum likelihood estimation was implemented using the Stochastic Approximation of the Expectation-Maximization algorithm to estimate the parameters. This study used the Centre of the AIDS Programme of Research in South Africa (CAPRISA) 002 Acute Infection Study data. In this study, the response variable is the longitudinal CD4 count from HIV-infected patients who were initiated on Highly Active Antiretroviral Therapy (HAART), and the explanatory variables are relevant baseline characteristics of the patients.ResultsThe analysis obtained robust parameters estimates at various locations of the conditional distribution. For instance, our result showed that baseline BMI (at [Formula: see text] 0.05: [Formula: see text]), baseline viral load (at [Formula: see text] 0.05: [Formula: see text] [Formula: see text]), and post-HAART initiation (at [Formula: see text] 0.05: [Formula: see text]) were major significant factors of CD4 count across fitted quantiles.ConclusionsCD4 cell recovery in response to post-HAART initiation across all fitted quantile levels was observed. Compared to HIV-infected patients with low viral load levels at baseline, HIV-infected patients enrolled in the treatment with a high viral load level at baseline showed a significant negative effect on CD4 cell counts at upper quantiles. HIV-infected patients registered with high BMI at baseline had improved CD4 cell count after treatment, but physicians should not ignore this group of patients clinically. It is also crucial for physicians to closely monitor patients with a low BMI before and after starting HAART.

Dataset Information

Morbidity and mortality according to latest CD4+ cell count among HIV positive individuals in South Africa who enrolled in project Phidisa.

Background

Methods and findings

Conclusion

Publications

Morbidity and mortality according to latest CD4+ cell count among HIV positive individuals in South Africa who enrolled in project Phidisa.

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