Early mortality and AIDS progression despite high initial antiretroviral therapy adherence and virologic suppression in Botswana.

BACKGROUND: Adverse outcomes occurring early after antiretroviral therapy (ART) initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana. METHODS: This prospective cohort study of 402 ART-naïve, HIV-infected adults initiating ART at a public HIV clinic in Gaborone, Botswana evaluated the relationship between suboptimal early ART adherence and HIV treatment outcomes in the initial months after ART initiation. Early adherence during the interval between initial ART dispensation and first ART refill was calculated using pill counts. In the primary analysis patients not returning to refill and those with adherence <0.95 were considered to have suboptimal early adherence. The primary outcome was death or loss to follow-up during the first 6 months of ART; a secondary composite outcome included the primary outcome plus incident opportunistic illness (OIs) and virologic failure. We also calculated the percent of early adverse outcomes theoretically attributable to suboptimal early adherence using the population attributable risk percent (PAR%). RESULTS: Suboptimal early adherence was independently associated with loss to follow-up and death (adjusted OR 2.3, 95% CI 1.1-4.8) and with the secondary composite outcome including incident OIs and virologic failure (adjusted OR 2.6, 95% CI 1.4-4.7). However, of those with early adverse outcomes, less than one-third had suboptimal adherence and approximately two-thirds achieved virologic suppression. The PAR% relating suboptimal early adherence and primary and secondary outcomes were 14.7% and 17.7%, respectively. CONCLUSIONS: Suboptimal early adherence was associated with poor outcomes, but most early adverse outcomes occurred in patients with optimal early adherence. Clinical care and research efforts should focus on understanding early adverse outcomes that occur despite optimal adherence.

Depression among HIV-positive individuals in Botswana: a behavioral surveillance.

This study examined incidence of depression in HIV-positive individuals in Botswana. One hundred and twenty HIV-positive individuals were administered a measure of daily activities and two measures of depression. Twenty four to 38% were diagnosed with depression, suicidal ideation ranged from 9 to 12%, with a positive correlation between scores on the two depression measures. Depression was associated with greater impairment in activities of daily living, especially the ability to take medication. These instruments can diagnose depression in persons living with HIV in developing countries, which will help to target those at risk for poor adherence, and will enable better allocation of limited resources.

In-hospital mortality of HIV-infected cryptococcal meningitis patients with C. gattii and C. neoformans infection in Gaborone, Botswana.

The clinical presentations and outcomes of cryptococcal meningitis (CM) may be associated with the cryptococcal species causing the infections. To evaluate clinical differences between CM caused by C. neoformans and Cryptococcus gattii, we examined outcomes in HIV-infected adults with CM admitted to Princess Marina Hospital in Gaborone, Botswana. Among HIV-infected adults with CM, we found that 29 of 96 (30%) patients were infected with C. gattii, but species type was not associated with in-hospital mortality [mortality for C. gattii: 5 of 29 (17%) vs C. neoformans: 13 of 67 (19%); OR = 0.87 (95% CI 0.28 to 2.70)]. The proportion of C. gattii infection among this HIV-infected cohort in Botswana is the highest reported to date, but we found no difference between C. gattii and C. neoformans in clinical presentation or in-hospital mortality.

Neurocognitive impairment among HIV-positive individuals in Botswana: a pilot study.

BACKGROUND: The primary objective of this study was to determine the prevalence of neurocognitive impairment among HIV-positive individuals in Botswana, using the International HIV Dementia Scale (IHDS). We also compared performance on the IHDS with performance on tests of verbal learning/memory and processing speed, and investigated the association between performance on the IHDS and such variables as depression, age, level of education and CD4 count. METHODS: We conducted a cross-sectional study of 120 HIV-positive individuals randomly selected from an outpatient HIV clinic in Gaborone, Botswana. Patients provided a detailed clinical history and underwent neuropsychological testing; measures of depression, daily activities and subjective cognitive complaints were recorded. RESULTS: Despite the fact that 97.5% of subjects were receiving highly active antiretroviral therapy (HAART), 38% met criteria for dementia on the IHDS, and 24% were diagnosed with major depressive disorder. There was a significant association between neurocognitive impairment as measured by the IHDS and performance on the other two cognitive measures of verbal learning/memory and processing speed. Level of education significantly affected performance on all three cognitive measures, and age affected processing speed and performance on the IHDS. Depression and current CD4 count did not affect performance on any of the cognitive measures. CONCLUSIONS: The prevalence of neurocognitive impairment in HIV-positive individuals in Botswana is higher than expected, especially since almost all of the subjects in this study were prescribed HAART. This suggests the need to reconsider the timing of introduction of antiretroviral therapy in developing countries where HAART is generally not administered until the CD4 cell count has dropped to 200/mm3 or below. The contribution of other factors should also be considered, such as poor central nervous system penetration of some antiretrovirals, drug resistance, potential neurotoxicity, and co-morbidities. Memory impairment and poor judgment may be underlying causes for behaviours that contribute to the spread of HIV and to poor adherence. It is important to identify these neurobehavioural complications of HIV so that effective treatments can be developed.