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Sub-Saharan Africa, which has about 12% of the global population, is home to almost 70% of individuals infected with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). A recent survey by the Ugandan Ministry of Health has found the HIV prevalence rate to be approximately 7% in sexually active adults. The predominant HIV subtypes present in Uganda are A and D. Health care resources are well planned but often lack human and fiscal resources. Uganda has adopted the World Health Organization (WHO) “3 by 5” global strategy for the introduction of antiretroviral therapy and has surpassed the target. Neurological complications of the HIV virus are common and often have devastating consequences. A recent study in Kampala found the rate of HIV dementia and peripheral neuropathy at 31% and 47%, respectively. Further studies are urgently required to determine the natural history and treatment outcomes of both these common HIV complications. [ABSTRACT FROM AUTHOR]

Depression is common following HIV infection and often improves after ART initiation. We aimed to identify distinct dimensions of depression that change following ART initiation in persons with HIV (PWH) with minimal comorbidities (e.g., illicit substance use) and no psychiatric medication use. We expected that dimensional changes in improvements in depression would differ across PWH. In an observational cohort in Rakai, Uganda, 312 PWH (51% male; mean age = 35.6 years) completed the Center for Epidemiologic Studies-Depression (CES-D) scale before and up to 2 years after ART initiation. Twenty-two percent were depressed (CES-D scores ≥ 16) pre-ART that decreased to 8% after ART. All CES-D items were used in a latent class analysis to identify subgroups with similar change phenotypes. Two improvement phenotypes were identified: affective-symptom improvement (n = 58, 19%) and mixed-symptom improvement (effort, appetite, irritability; n = 41, 13%). The affect-improvement subgroup improved on the greatest proportion of symptoms (76%). A third subgroup was classified as no-symptom changes (n = 213, 68%) as they showed no difference is symptom manifestation from baseline (93% did not meet depression criteria) to post-ART. Factors associated with subgroup membership in the adjusted regression analysis included pre-ART self-reported functional capacity, CD4 count, underweight BMI, hypertension, female sex(P's < 0.05). In a subset of PWH with CSF, subgroup differences were seen on Aβ-42, IL-13, and IL-12. Findings support that depression generally improves following ART initiation; however, when improvement is seen the patterns of symptom improvement differ across PWH. Further exploration of this heterogeneity and its biological underpinning is needed to evaluate potential therapeutic implications of these differences., (© 2021. Journal of NeuroVirology, Inc.)

We investigated the prevalence and risk factors for frailty among people with HIV (PWH) in rural Uganda (n = 55, 47% male, mean age 44 years). Frailty was defined according to the Fried criteria with self-reported physical activity level replacing the Minnesota Leisure Time Activity Questionnaire. Alternate classifications for physical activity utilized were the sub-Saharan Africa Activity Questionnaire and the International Physical Activity Questionnaire. Eleven participants (19%) were frail. Frail participants were older (p < 0.001), less likely to be on antiretroviral therapy (p = 0.03), and had higher rates of depression (p < .001) and HIV-associated neurocognitive disorder (p = 0.003). Agreement between physical activity measures was sub-optimal. Prevalence of frailty was high among PWH in rural Uganda, but larger sample sizes and local normative data are needed.

People with HIV (PWH) taking antiretroviral therapy (ART) have persistent cognitive impairment. The prevalence of cognitive impairment is higher in women with HIV (WWH) compared to men with HIV (MWH), possibly due to sex differences in immune function. Here we report sex differences in cerebrospinal fluid (CSF) immune markers in relation to cognitive performance. A subset of 83 PWH on ART (52% WWH; mean age = 37.6 years, SD = 7.9) from the Rakai community cohort study Cohort and Rakai Health Sciences Program supported clinics in rural Uganda completed a neuropsychological (NP) assessment and a lumbar puncture. CSF was used to measure 16 cytokines/chemokines. Individual NP test z-scores were generated based on local normative data. A series of least absolute shrinkage and selection operator (lasso) regressions examined associations between CSF inflammatory markers and NP outcomes. Overall, there were no sex differences in CSF inflammatory marker levels. However, MWH displayed more associations between inflammatory markers and cognitive performance than WWH. Among MWH, inflammatory markers were associated with a number of cognitive domains, including attention, processing speed, fluency, executive function, learning and memory. MIP-1β, INF-γ, GM-CSF, IL-7 and IL-12p70 were associated with multiple domains. Among WWH, few inflammatory markers were associated cognition. Degree of associations between CSF inflammatory biomarkers and cognitive performance varied by sex in this young, ART-treated, Ugandan cohort. Further investigation into sex-specific inflammatory mechanisms of cognitive impairment among PWH is warranted to inform sex-specific management strategies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Neurological disorders are common in sub-Saharan African, but accurate neuroepidemiologic data are lacking from the region. We assessed a neuroepidemiological screening tool in a rural Ugandan cohort with high HIV prevalence., Methods: Participants were recruited from the Rakai Neurology Study in rural Rakai District, Uganda. A nurse administered the tool and a sociodemographic survey. 100 participants returned for validation examinations by a neurologist (validation cohort). The diagnostic utility and validity of the instrument were calculated and characteristics of those with and without neurological disorders compared., Results: The tool was administered to 392 participants, 48% female, 33% people with HIV, average age 35.1 ± 8.5 years. 33% of the study cohort screened positive for neurologic disorders. These participants were older [mean (SD): 38.3 (9.7) vs. 33.5 (7.1) years, p < 0.001], had a lower Karnofsky score [89.8 (8.4) vs. 93.9 (7.5), p < 0.001] and had a lower body mass index [21.8 (3.3) vs. 22.8 (3.7), p = 0.007] than those who screened negative. Amongst the validation cohort, 54% had a neurological abnormality of which 46% were symptomatic. The tool was 57% sensitive and 74% specific for detecting any neurological abnormality and 80% sensitive and 69% specific for symptomatic abnormalities., Conclusions: We found a lower sensitivity and similar specificity for the screening tool compared with two previous studies. The lower validity in this study was likely due in part to the high percentage of asymptomatic neurological abnormalities detected. This screening tool will require further refinement and cultural contextualization before it can be widely implemented across new populations., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: HIV-associated neurocognitive disorders remain prevalent despite effective antiretroviral therapy (ART), but there are limited longitudinal data on people living with HIV (PLWH) in sub-Saharan Africa. We examined neuropsychological (NP) performance in PLWH in a longitudinal study in Uganda., Methods: Participants enrolled through the Rakai Community Cohort Study (400 ART-naive PLWH and 400 matched HIV-negative persons) were administered NP assessments. In 2017, PLWH who had initiated ART underwent a 2-year follow-up assessment. Demographically adjusted Z-scores for each NP test were established using data from the HIV- controls. Multivariable linear and logistic regressions were conducted to examine group differences in NP performance. Mixed-effects regressions were conducted to examine ART-related changes in NP outcomes., Results: Of 333 PLWH who returned for their 2-year follow-up visit, 312 (94%) had initiated ART. Those on ART had a mean age of 35.6 years (SD ± 8.5 years) and mean education of 5.4 years (SD ± 3.3 years); 49% were women. ART-associated NP improvements occurred in verbal learning and memory (P's < 0.05), motor (P's < 0.01), and some measures of processing speed (P = 0.002), whereas there were declines in attention/working memory (P's < 0.001) and semantic fluency (P < 0.001). Pre-ART CD4 count and efavirenz use were associated with a more impaired change in NP performance., Conclusions: PLWH in this resource-limited setting showed improved neurocognitive performance on most NP tests after ART initiation. However, the declines in attention/working memory and fluency performance, as well as relationship to efavirenz, warrant further study.

The Veterans Aging Cohort Study (VACS) Index has been associated with HIV-associated neurocognitive disorder (HAND) in some populations but has not been studied in sub-Saharan Africa. We investigated whether the VACS Index is associated with HAND in a rural population in Rakai, Uganda. HIV-infected (HIV+) adults on antiretroviral therapy underwent a neurocognitive battery for determination of HAND stage using Frascati criteria. VACS component scores were recorded for all participants. Out of 156 study participants, HAND stages were 49% normal cognition, 15% asymptomatic neurocognitive impairment, 31% minor neurocognitive disorder, and 7% HIV-associated dementia. There was no significant association between VACS Index and any HAND stage. In this first study of the VACS Index in sub-Saharan Africa, we found no association between VACS Index score and HAND.

Serum interleukin-6 (IL-6) and D-dimer have been associated with multiple adverse outcomes in HIV-infected (HIV+) individuals, but their association with neuropsychiatric outcomes, including HIV-associated neurocognitive disorder (HAND) and depression, headaches, and peripheral neuropathy have not been investigated. Three hundred ninety-nine HIV+ antiretroviral therapy (ART)-naïve adults in Rakai, Uganda, were enrolled in a longitudinal cohort study and completed a neurological evaluation, neurocognitive assessment, and venous blood draw. Half of the participants had advanced immunosuppression (CD4 count < 200 cells/μL), and half had moderate immunosuppression (CD4 count 350-500 cells/μL). All-cause mortality was determined by verbal autopsy within 2 years. HAND was determined using Frascati criteria, and depression was defined by the Center for Epidemiologic Studies-Depression (CES-D) scale. Neuropathy was defined as the presence of > 1 neuropathy symptom and > 1 neuropathy sign. Headaches were identified by self-report. Serum D-dimer levels were determined using ELISA and IL-6 levels using singleplex assays. Participants were 53% male, mean age 35 + 8 years, and mean education 5 + 3 years. Participants with advanced immunosuppression had significantly higher levels of IL-6 (p < 0.001) and a trend toward higher D-dimer levels (p = 0.06). IL-6 was higher among participants with HAND (p = 0.01), with depression (p = 0.03) and among those who died within 2 years (p = 0.001) but not those with neuropathy or headaches. D-dimer did not vary significantly by any outcome. Systemic inflammation as measured by serum IL-6 is associated with an increased risk of advanced immunosuppression, all-cause mortality, HAND, and depression but not neuropathy or headaches among ART-naïve HIV+ adults in rural Uganda.

Considerable heterogeneity exists in patterns of neurocognitive change in people with HIV (PWH). We examined heterogeneity in neurocognitive change trajectories from HIV diagnosis to 1-2 years post-antiretroviral therapy (ART). In an observational cohort study in Rakai, Uganda, 312 PWH completed a neuropsychological (NP) test battery at two-time points (ART-naïve, 1-2 years post-ART initiation). All NP outcomes were used in a latent profile analysis to identify subgroups of PWH with similar ART-related neurocognitive change profiles. In a subset, we examined subgroup differences pre-ART on cytokine and neurodegenerative biomarkers CSF levels. We identified four ART-related change subgroups: (1) decline-only (learning, memory, fluency, processing speed, and attention measures), (2) mixed (improvements in learning and memory but declines in attention and executive function measures), (3) no-change, or (4) improvement-only (learning, memory, and attention measures). ART-related NP outcomes that are most likely to change included learning, memory, and attention. Motor function measures were unchanged. Subgroups differed on eight of 34 pre-ART biomarker levels including interleukin (IL)-1β, IL-6, IL-13, interferon-γ, macrophage inflammatory protein-1β, matrix metalloproteinase (MMP)-3, MMP-10, and platelet-derived growth factor-AA. The improvement-only and mixed subgroups showed lower levels on these markers versus the no-change subgroup. These findings provide support for the need to disentangle heterogeneity in ART-related neurocognitive changes, to focus on higher-order cognitive processes (learning, memory, attention) as they were most malleable to change, and to better understand why motor function remained unchanged despite ART treatment. Group differences in pre-ART CSF levels provide preliminary evidence of biological plausibility of neurocognitive phenotyping.

Assessment of an individual's functional status, as measured by activities of daily living (ADL), is an essential element in the diagnosis of HIV-associated neurocognitive disorders (HAND) but individuals with cognitive impairment may not accurately report ADL. We assessed agreement between self- and caregiver-reported ADL in HIV-positive persons. Antiretroviral therapy (ART)-naïve HIV-positive persons (n = 321) and HIV-negative controls (n = 134) in Rakai, Uganda, completed neurocognitive tests and an ADL questionnaire. Co-resident relatives ("caregivers") were independently administered the ADL questionnaire to determine their perception of the participant's ADL. The relationship between neurocognitive impairment and participant-caregiver agreement was assessed using kappa statistics. Regression was used to estimate adjusted prevalence ratios (AdjPR) of participant-caregiver agreement on disability scores. Relative to HIV-negative adults, HIV-positive participants scoring at least 1 standard deviation (SD) below the norm on 2 or more neurocognitive tests were classified as having mild neurocognitive impairment and those scoring at least 2 SD below the norm on 2 or more neurocognitive tests were classified as having moderate-to-severe. Mean age was 36 years (SD 8.9), and 53% of participants were male. The rate of ADL agreement between participants and caregivers was 77% for HIV-positive and 87% for HIV-negative participants (AdjPR = 0.89, 95% CI 0.81-0.97, p = .01). Among HIV-positive participants, 41% had moderate neurocognitive impairment, 15% had severe neurocognitive impairment, and 44% were normal. For moderate neurocognitive impairment, the rate of ADL agreement was 69% and for severe neurocognitive impairment, it was 66%. Compared to non-impaired HIV-positive participants (86% ADL agreement), ADL agreement was lower with moderate impairment (AdjPR = 0.89, 95%CI 0.81-0.98, p = .023) and severe impairment (AdjPR = 0.77, 95%CI 0.63-0.95, p = .014). Gender, education and CD4 count were not associated with ADL agreement. HIV-positive persons with neurocognitive impairment have lower agreement with caregivers' reports of ADL than HIV-positive persons without cognitive impairment.

Background: Combination antiretroviral therapy (ART) improves HIV-associated neurocognitive disorder (HAND) stage in the United States where subtype B predominates, but the effect of ART and subtype on HAND stage in individuals in Uganda with subtypes D and A is largely unknown., Setting: A community-based cohort of participants residing in Rakai, Uganda., Methods: Three hundred ninety-nine initially ART-naive HIV-seropositive (HIV+) individuals were followed up over 2 years. Neurological and neuropsychological tests and functional assessments were used to determine HAND stage. Frequency and predictors of HAND and HIV-associated dementia (HAD) were assessed at baseline and at follow-up after ART initiation in 312 HIV+ individuals. HIV subtype was determined from gag and env sequences., Results: At 2-year follow-up, HAD frequency among HIV+ individuals on ART (n = 312) decreased from 13% to 5% (P < 0.001), but the overall frequency of HAND remained unchanged (56%-51%). Subtype D was associated with higher rates of impaired cognition (global deficit score ≥ 0.5) compared with HIV+ individuals with subtype A (55% vs. 24%) (P = 0.008). Factors associated with HAD at baseline were older age, depression, and plasma HIV viral load >100,000 copies/mL. At follow-up, age and depression remained significantly associated with HAD., Conclusions: HIV+ individuals on ART in rural Uganda had a significant decrease in the frequency of HAD, but HAND persists after 2 years on ART. The current guideline of immediate ART initiation after HIV diagnosis is likely to greatly reduce HAD in sub-Saharan Africa. Further studies of the effect of HIV subtype and neurocognitive performance are warranted.

We investigated whether vitamin D is associated with HIV-associated neurocognitive disorder (HAND). HIV-infected (HIV+) antiretroviral therapy (ART)-naïve adults in rural Uganda underwent a neurocognitive battery for determination of HAND stage at baseline and after 2 years. Baseline serum 25-hydroxyvitamin D (25OH-D) and serum and cerebrospinal fluids (CSF) vitamin D-binding protein (VDBP) were obtained. Of the 399 participants, 4% (n = 16) were vitamin D deficient (25OH-D < 20 ng/mL). There was no association between 25OH-D, serum or CSF VDBP, and HAND stage at baseline or follow-up. Future studies in a population with higher levels of vitamin D deficiency may be warranted.

Headache is common, but its prevalence and impact in sub-Saharan Africa and especially in HIV+ individuals is relatively unknown. We sought to determine the prevalence and functional impact of headache among HIV-infected (HIV+) adults in a cross-sectional observational cohort study in rural Rakai District, Uganda. Participants completed a sociodemographic survey, depression screen, functional status assessments, and answered the headache screening question, "Do you have headaches?" Participants responding affirmatively were assessed with the ID Migraine tool for diagnosis of migraine and Headache Impact Test-6 to determine functional impact of headache. Characteristics of participants with and without headaches and with and without functional impairment were compared using t tests for continuous variables, chi-square tests for categorical variables, and multivariate logistic regression. Of 333 participants, 51% were males, mean age was 37 (SD 9) years, 94% were on antiretroviral therapy (ART) and mean CD4 count was 403 (SD 198) cells/μL. Headache prevalence was 28%. Among those reporting headache, 19% met criteria for migraine, 55% reported functional impairment, and 37% reported substantial or severe impact of headache. In multivariate analyses, female sex (odds ratio (OR) 2.58) and depression (OR 2.49) were associated with increased odds and ART (OR 0.33) with decreased odds of headache. Participants with substantial/severe functional impact were more likely to meet criteria for depression (32% vs 9%). In conclusion, headache prevalence in HIV+ rural Ugandans was lower than global averages but still affected more than one quarter of participants and was associated with significant functional impairment.

HIV-associated neurocognitive disorders (HAND) are a common neurological manifestation of HIV infection. A previous study suggested that HIV dementia may be more common among patients with subtype D virus than among those with subtype A virus among HIV+ individuals with advanced immunosuppression. We conducted a study to evaluate the frequency of HIV dementia, and the association of HIV dementia with HIV subtype and compartmentalization among HIV+ individuals with moderate and advanced immunosuppression (CD4 lymphocyte count >150 cells/μL and <250 cells/μL). The study enrolled 117 antiretroviral naïve HIV+ individuals in Kampala, Uganda. HIV+ individuals received neurological, neuropsychological testing, and functional assessments, and gag and gp41 regions were subtyped. Subjects were considered infected with a specific subtype if both regions analyzed were from the same subtype. 41% of the HIV+ individuals had HIV dementia (mean CD4 lymphocyte count = 233 cells/μL). 67 individuals had subtype A, 25 individuals had subtype D, 24 individuals were classified as A/D recombinants, and one individual had subtype C. There was no difference in the frequency of HIV dementia when stratified by HIV subtype A and D and no association with compartmentalization between the cerebrospinal fluid and peripheral blood. These results suggest that HIV dementia is common in HIV+ individuals in Uganda. There was no association between HIV subtype and dementia among HIV+ individuals with moderate and advanced immunosuppression. Future studies should be performed to confirm these results.

This study was conducted to evaluate longitudinal neuropsychological testing performance over a 12-month period among HIV+individuals, and to evaluate the impact of antiretroviral therapy (ART) initiation on neuropsychological test changes in Uganda. The study examined 77 HIV+individuals recruited from the Infectious Diseases Clinic at Makerere University, Uganda. They underwent detailed sociodemographic, medical history, immune status, functional, neurologic, and neuropsychological evaluations at baseline and 12 months later. Thirty-one individuals initiated ART (ART group) after their baseline visit, whereas 46 individuals were not placed on ART (no-ART group) during those 12 months. Paired samples t-tests were used to evaluate longitudinal changes in neuropsychological test performance for the entire sample, as well as for groups defined by ART initiation and baseline neurocognitive status. The study evaluated 77 HIV individuals (62 % women, mean age=37 years, mean education=8 years, mean CD4 count=235 cells/μl). Both the ART and no-ART groups showed significant improvements in tests of verbal memory, executive functioning, motor, and psychomotor speed performance, as well as depression symptoms. The ART group had significant improvements in CD4 count over the 12-month period (p<0.001), whereas the no-ART group had no CD4 count improvement. ART use is associated with improvements in cognitive functioning among HIV+individuals in Uganda. However, these improvements did not appear to be higher than those seen among HIV+individuals who did not initiate ART. Possible reasons for this include practice effects among the no-ART group as well as improvements in their mood and overall quality of life.

Objective: To evaluate the efficacy and safety of minocycline in the management of HIV-associated cognitive impairment., Methods: We enrolled HIV-positive participants with a CD4 count of 250 to 500 cells/μL in a randomized, double-blind, placebo-controlled study. They received 100 mg of minocycline or matching placebo orally every 12 hours for 24 weeks. Cognitive function was measured using the Uganda neuropsychological test battery summary measure (U NP Sum) and the Memorial Sloan-Kettering (MSK) scale. The primary efficacy measure was the 24-week change in an average of 9 standardized U NP Sum z scores., Results: Seventy-three participants were enrolled. Of these, 90% were female, 49% were between the ages 30 and 39 years, and 74% had 6 or more years of education. One participant had MSK score of stage 1 (i.e., mild HIV dementia), and 72 participants had MSK stage 0.5 (i.e., equivocal or subclinical dementia) at the baseline evaluation. The minocycline effect on the 24-week change of the U NP Sum compared with placebo was 0.03 (95% confidence interval -0.51, 0.46; p = 0.37)., Conclusion: Minocycline was safe and well tolerated in HIV-positive individuals. However, it did not improve HIV-associated cognitive impairment., Classification of Evidence: This study provides Class II evidence that 100 mg of minocycline given orally every 12 hours for 24 weeks had no significant effect compared with placebo in the improvement of cognitive function in antiretroviral therapy-naive, HIV-positive patients.

Background: Among patients with HIV infection, depression is the most frequently observed psychiatric disorder. The presence of depressive symptoms and cognitive dysfunction among HIV patients has not been well studied in Sub-Saharan Africa. Initiation of highly active antiretroviral therapy (HAART) may have an effect on the prevalence and the change over time of depression symptoms and cognitive impairment among HIV-positive individuals., Methods: We recruited 102 HIV-positive individuals at risk of cognitive impairment who were initiating HAART and 25 HIV-negative individuals matched for age and education. Depression was assessed using the Centre for Epidemiologic Studies Depression Scale (CES-D). Neurocognitive assessment included the International HIV Dementia Scale (IHDS), an 8 test neuropsychological battery and the Memorial Sloan Kettering scale. Assessments were carried out at 0, 3 and 6 months., Results: The HIV-positive group had more respondents with CES-D score > 16 than the HIV-negative group at all 3 clinic visits (54%Vs 28%; 36% Vs 13%; and 30% Vs 24% respectively; all p < 0.050 OR 2.86, 95% CI: 1.03, 7.95, p = 0.044). The HIV positive group had higher likelihood for cognitive impairment (OR 8.88, 95% CI 2.64, 29.89, p < 0.001). A significant decrease in the mean scores on the CES-D (p = 0.002) and IHDS (p = 0.001) occurred more in the HIV-positive group when compared to the HIV-negative group. There was no association between clinical Memorial Sloan Kettering score and depression symptoms (p = 0.310) at baseline., Conclusion: Depression symptomatology is distinct and common among cognitively impaired HIV patients. Therefore individuals in HIV care should be screened and treated for depression.

Background: In the United States, clade B is the predominant human immunodeficiency virus (HIV) subtype, whereas in sub-Saharan Africa, clades A, C, and D are the predominant subtypes. HIV subtype may have an impact on HIV disease progression. The effect of HIV subtype on the risk of dementia has, to our knowledge, not been examined. The objective of this study was to examine the relationship between HIV subtype and the severity of HIV-associated cognitive impairment among individuals initiating antiretroviral therapy in Uganda., Methods: Sixty antiretroviral-naive HIV-infected individuals with advanced immunosuppression who were at risk of HIV-associated cognitive impairment underwent neurological, neuropsychological, and functional assessments, and gag and gp41 regions were subtyped. Subtype assignments were generated by sequence analysis using a portion of the gag and gp41 regions., Results: Thirty-three HIV-infected individuals were infected with subtype A, 2 with subtype C, 9 with subtype D, and 16 with A/D recombinants. Eight (89%) of 9 HIV-infected individuals with subtype D had dementia, compared with 7 (24%) of 33 HIV-infected individuals with subtype A (P = .004)., Conclusions: These results suggest that, in untreated HIV-infected individuals with advanced immunosuppression who are at risk of developing HIV-associated cognitive impairment, HIV dementia may be more common among patients infected with subtype D virus than among those infected with subtype A virus. These findings provide the first evidence, to our knowledge, to demonstrate that HIV subtypes may have a pathogenetic factor with respect to their capacity to cause cognitive impairment. Additional studies are needed to confirm this observation and to define the mechanism by which subtype D leads to an increased risk of neuropathogenesis.

Background: The frequency of HIV dementia in a recent study of HIV+ individuals at the Infectious Disease Institute in Kampala, Uganda, was 31%. Coformulated generic drugs, which include stavudine, are the most common regimens to treat HIV infection in Uganda and many other parts of Africa., Objective: To evaluate the benefits and risks of stavudine-based highly active antiretroviral therapy (HAART) for HIV-associated cognitive impairment and distal sensory neuropathy. The study compared neuropsychological performance changes in HIV+ individuals initiating HAART for 6 months and HIV- individuals receiving no treatment for 6 months. The risk of antiretroviral toxic neuropathy as a result of the initiation of stavudine-based HAART was also examined., Methods: At baseline, 102 HIV+ individuals in Uganda received neurologic, neuropsychological, and functional assessments; began HAART; and were followed up for 6 months. Twenty-five HIV- individuals received identical clinical assessments and were followed up for 6 months., Results: In HIV+ individuals, there was improvement in verbal memory, motor and psychomotor speed, executive thinking, and verbal fluency. After adjusting for differences in sex, HIV+ individuals demonstrated significant improvement in the Color Trails 2 test (p = 0.025) compared with HIV- individuals. Symptoms of neuropathy developed in 38% of previously asymptomatic HIV+ patients after initiation of the stavudine-based HAART., Conclusions: After the initiation of highly active antiretroviral therapy (HAART) including stavudine, HIV+ individuals with cognitive impairment improve significantly as demonstrated by improved performance on a test of executive function. However, peripheral neurotoxicity occurred in 30 patients, presumably because of stavudine-based HAART, suggesting the need for less toxic therapy.

Background: Few studies have examined cognitive functioning of HIV positive patients in sub-Saharan Africa. It cannot be assumed that HIV positive patients in Africa exhibit the same declines as patients in high-resource settings, since there are differences that may influence cognitive functioning including nutrition, history of concomitant disease, and varying HIV strains, among other possibilities. Part of the difficulty of specifying abnormalities in neuropsychological functioning among African HIV positive patients is that there are no readily available African normative databases. The purpose of the current study was to evaluate the pattern of neuropsychological performance in a sample of HIV positive patients in comparison to HIV negative control subjects in Uganda., Methods: The neuropsychological test scores of 110 HIV positive patients (WHO Stage 2, n = 21; WHO Stage 3, n = 69; WHO Stage 4, n = 20) were contrasted with those of 100 control subjects on measures of attention/concentration, mental flexibility, learning/memory, and motor functioning., Results: Analysis of covariance (ANCOVA) revealed significant group differences on measures of verbal learning and memory, speed of processing, attention and executive functioning between HIV seropositive and seronegative subjects., Conclusion: Ugandan patients with HIV demonstrated relative deficits on measures of verbal learning and memory, speed of processing, attention, and executive functioning compared to HIV negative controls. These results from a resource limited region where clades A and D are prevalent are consistent with previous findings in the developed world where clade B predominates.

Objective: To measure the frequency and associated risk factors of HIV dementia in an HIV clinic in Kampala, Uganda., Methods: We systematically sampled 78 HIV-seropositive (HIV+) patients from an ambulatory HIV clinic. Participants underwent detailed sociodemographic, medical history, functional, neurologic, and neuropsychological evaluations. One hundred HIV-negative patients were recruited to provide normative data for the neuropsychological tests. A logistic regression model was constructed to determine risk factors associated with the diagnosis of HIV dementia., Results: Thirty-one percent (24 of 78) of the HIV+ patients had HIV dementia. Advanced age and low CD4(+) T-lymphocyte count (CD4 count) were the only variables identified as significant risk factors in the logistic regression model. Each additional 10 years of age conferred a greater than twofold risk of HIV dementia (OR 2.06, 95% CI: 1.05 to 4.07; p < 0.05). Reduced levels of CD4 count (100 cells/muL decrement) was associated with a 60% increase in the odds of having HIV dementia (OR 1.6, 95% CI: 1.04 to 2.33; p < 0.05)., Conclusion: HIV dementia is common in HIV-seropositive Ugandan individuals attending an AIDS clinic. It is more frequently associated with patients of advanced age and decreased CD4 count.