Paula Braitstein

Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries

BACKGROUND Highly active antiretroviral therapy (HAART) is being scaled up in developing countries. We compared baseline characteristics and outcomes during the first year of HAART between HIV-1-infected patients in low-income and high-income settings. METHODS 18 HAART programmes in Africa, Asia, and South America (low-income settings) and 12 HIV cohort studies from Europe and North America (high-income settings) provided data for 4810 and 22,217, respectively, treatment-naïve adult patients starting HAART. All patients from high-income settings and 2725 (57%) patients from low-income settings were actively followed-up and included in survival analyses. FINDINGS Compared with high-income countries, patients starting HAART in low-income settings had lower CD4 cell counts (median 108 cells per muL vs 234 cells per muL), were more likely to be female (51%vs 25%), and more likely to start treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (70%vs 23%). At 6 months, the median number of CD4 cells gained (106 cells per muL vs 103 cells per muL) and the percentage of patients reaching HIV-1 RNA levels lower than 500 copies/mL (76%vs 77%) were similar. Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20,532 person-years). The adjusted hazard ratio (HR) of mortality comparing low-income with high-income settings fell from 4.3 (95% CI 1.6-11.8) during the first month to 1.5 (0.7-3.0) during months 7-12. The provision of treatment free of charge in low-income settings was associated with lower mortality (adjusted HR 0.23; 95% CI 0.08-0.61). INTERPRETATION Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries. Timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART, might reduce this excess mortality.

Antiretroviral therapy in resource-limited settings 1996 to 2006: patient characteristics, treatment regimens and monitoring in sub-Saharan Africa, Asia and Latin America

Objectives  To describe temporal trends in baseline clinical characteristics, initial treatment regimens and monitoring of patients starting antiretroviral therapy (ART) in resource‐limited settings.

Gender and the use of antiretroviral treatment in resource-constrained settings: findings from a multicenter collaboration.

AIMS To compare the gender distribution of HIV-infected adults receiving highly active antiretroviral treatment (HAART) in resource-constrained settings with estimates of the gender distribution of HIV infection; to describe the clinical characteristics of women and men receiving HAART. METHODS The Antiretroviral Therapy in Lower-Income Countries, ART-LINC Collaboration is a network of clinics providing HAART in Africa, Latin America, and Asia. We compared UNAIDS data on the gender distribution of HIV infection with the proportions of women and men receiving HAART in the ART-LINC Collaboration. RESULTS Twenty-nine centers in 13 countries participated. Among 33,164 individuals, 19,989 (60.3%) were women. Proportions of women receiving HAART in ART-LINC centers were similar to, or higher than, UNAIDS estimates of the proportions of HIV-infected women in all but two centers. There were fewer women receiving HAART than expected from UNAIDS data in one center in Uganda and one center in India. Taking into account heterogeneity across cohorts, women were younger than men, less likely to have advanced HIV infection, and more likely to be anemic at HAART initiation. CONCLUSIONS Women in resource-constrained settings are not necessarily disadvantaged in their access to HAART. More attention needs to be paid to ensuring that HIV-infected men are seeking care and starting HAART.

Discordant Immunologic and Virologic Responses to Highly Active Antiretroviral Therapy Are Associated With Increased Mortality and Poor Adherence to Therapy

Objective:To examine the independent association of discordant virologic and immunologic responses to highly active antiretroviral therapy (HAART) with mortality. Methods:A population-based study of 1527 treatment-naive individuals initiating HAART used Cox proportional hazards modeling to determine the independent association of treatment response at 3 to 9 months with nonaccidental mortality. Logistic regression was used to examine associations with discordant responses. Results:Viral load (VL)+/CD4− discordant responses were seen in 235 (15.4%) of subjects, and VL−/CD4+ responses were seen in 179 (11.7%) of subjects. In adjusted Cox regression models, discordant responses were found to be independently associated with an increased risk of mortality (VL+/CD4−: relative hazard [RH] = 1.87, 95% confidence interval [CI]: 1.15 to 3.04; VL−/CD4+: RH = 2.47, 95% CI: 1.54 to 3.95). VL+/CD4− discordance was found to be associated with increasing age, baseline HIV RNA load <100,000 copies/mL, baseline CD4 counts <50 cells/μL, the use of lamivudine (3TC)/zidovudine (ZDV), and poor adherence to therapy. VL−/CD4+ discordance was associated with younger age; injection drug use; baseline HIV RNA load >100,000 copies/mL; the use of 3TC/ZDV, didanosine (ddI)/3TC, or ddI/stavudine; and poor adherence to therapy. Conclusion:Discordant responses are independently associated with an increased risk of mortality and are, in turn, associated with poor adherence to therapy.

Cohort Profile: The international epidemiological databases to evaluate AIDS (IeDEA) in sub-Saharan Africa

In response to the HIV/AIDS pandemic in sub-Saharan Africa the African networks of IeDEA (International epidemiologic databases to Evaluate AIDS) aim to inform the scale-up of ART in the region through clinical and epidemiologic research. Funded by the National Institutes of Allergy and Infectious Diseases (NIAID) the objectives across the four African IeDEA regions (West Africa Central Africa East Africa and Southern Africa) are similar and cover all populations including pregnant women infants children adolescents and adult patients. They can be summarized as follows: (1) To prove robust evaluation of the delivery of ART in children adolescents and adults in sub-Saharan Africa with a focus on long-term program effectiveness and outcomes; (2) to describe the long-term temporal trends in regimen durability and tolerability and to examine monitoring strategies; (3) to describe important comorbidities and co-infections of HIV infection including malaria tuberculosis and cancer; (4) to examine the pregnancy- and HIV-related outcomes of women initiating ART during pregnancy and of infants exposed to HIV or ART in utero; (5) to develop and apply novel statistical methods to deal with missing data loss to follow-up competing risks and time-dependent confounding; (6) to establish procedures to link the HIV cohort data with other databases at local or national level. The present report provides an indicative summary of some of the major research themes and key findings as well as a discussion of the program’s strengths and weaknesses.

Impairments, activity limitations and participation restrictions: Prevalence and associations among persons living with HIV/AIDS in British Columbia

BackgroundTo measure the prevalence of and associations among impairments, activity limitations and participation restrictions in persons living with HIV in British Columbia to inform support and care programs, policy and research.MethodsA cross-sectional population-based sample of persons living with HIV in British Columbia was obtained through an anonymous survey sent to members of the British Columbia Persons With AIDS Society. The survey addressed the experience of physical and mental impairments, and the experience and level of activity limitations and participation restrictions. Associations were measured in three ways: 1) impact of types of impairment on social restriction; 2) impact of specific limitations on social restriction; and 3) independent association of overall impairments and limitations on restriction levels. Logistic regression was used to measure associations with social restriction, while ordinal logistic regression was used to measure associations with a three-category measure of restriction level.ResultsThe survey was returned by 762 (50.5%) of the BCPWA participants. Over ninety percent of the population experienced one or more impairments, with one-third reporting over ten. Prevalence of activity limitations and participation restrictions was 80.4% and 93.2%, respectively. The presence of social restrictions was most closely associated with mental function impairments (OR: 7.0 for impairment vs. no impairment; 95% CI: 4.7 – 10.4). All limitations were associated with social restriction. Among those with ≤ 200 CD4 cells/mm3, odds of being at a higher restriction level were lower among those on antiretrovirals (OR: 0.3 for antiretrovirals vs. no antiretrovirals; 95% CI: 0.1–0.9), while odds of higher restriction were increased with higher limitation (OR: 3.6 for limitation score of 1–5 vs. no limitation, 95%CI: 0.9–14.2; OR: 24.7 for limitation score > 5 vs. no limitation, 95%CI: 4.9–125.0). Among those with > 200 CD4 cells/mm3, the odds of higher restriction were increased with higher limitation (OR: 2.7 for limitation score of 1–5 vs. no limitation, 95%CI: 1.4–5.1; OR: 8.6 for limitation score > 5 vs. no limitation, 95%CI: 3.9–18.8), as well as by additional number of impairments (OR:1.2 for every additional impairment; 95% CI:1.1–1.3).ConclusionsThis population-based sample of people living with HIV has been experiencing extremely high rates of impairments, activity limitations and participation restrictions. Furthermore, the complex inter-relationships identified amongst the levels reveal lessons for programming, policy and research in terms of the factors that contribute most to a higher quality of life.

Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.

Background:In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia. Design and methods:Multicohort study of 17 ART programmes. All sites monitored CD4 cell count and had access to second-line ART and 10 sites monitored viral load. We compared times to switching, CD4 cell counts at switching and obtained adjusted hazard ratios for switching (aHRs) with 95% confidence intervals (CIs) from random-effects Weibull models. Results:A total of 20 113 patients, including 6369 (31.7%) patients from 10 programmes with access to viral load monitoring, were analysed; 576 patients (2.9%) switched. Low CD4 cell counts at ART initiation were associated with switching in all programmes. Median time to switching was 16.3 months [interquartile range (IQR) 10.1–26.6] in programmes with viral load monitoring and 21.8 months (IQR 14.0–21.8) in programmes without viral load monitoring (P < 0.001). Median CD4 cell counts at switching were 161 cells/μl (IQR 77–265) in programmes with viral load monitoring and 102 cells/μl (44–181) in programmes without viral load monitoring (P < 0.001). Switching was more common in programmes with viral load monitoring during months 7–18 after starting ART (aHR 1.38; 95% CI 0.97–1.98), similar during months 19–30 (aHR 0.97; 95% CI 0.58–1.60) and less common during months 31–42 (aHR 0.29; 95% CI 0.11–0.79). Conclusion:In resource-limited settings, switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with viral load monitoring compared with programmes without viral load monitoring.

Sexual violence among a cohort of injection drug users.

The objective of this study was to determine the prevalence of, and factors associated with, sexual violence in childhood, adolescence and adulthood, among injection drug using men and women. The Vancouver Injection Drug User Study is a prospective cohort of injection drug users (IDU) begun in 1996. The analysis included all individuals who completed the baseline questionnaire who responded to a question about sexual assault. Multivariate modeling was used to determine and to what extent a history of sexual violence at different ages is predictive of HIV risk and other health risk behaviors. HIV prevalence was calculated as the total current number of HIV-positive individuals in the cohort. Of the 1437 eligible individuals, 36% reported a lifetime history of sexual violence; 68% of women, and 19% of men (p<0.001). After adjusting for fixed sociodemographics, these individuals were more likely to have ever been in the sex trade, to knowingly share needles/rigs with HIV-positive people, to have attempted suicide, to have ever accidentally overdosed, to binge on alcohol, and to have been diagnosed with a mental disorder/disability. The prevalence of child sexual abuse in this cohort is 21%; 33% for women, and 13% for men. The data show a dose-response relationship between age at first sexual violence and most risk behaviors examined. These relationships are further mediated by gender. The prevalence of HIV among individuals who ever experienced sexual violence was 25%, compared to 19% among those who never experienced sexual violence (p=0.006). Sexual violence, and especially child sexual abuse, is highly prevalent among this cohort, particularly among women. Child sexual abuse has worse consequences for both genders than sexual violence later in life. Nevertheless, women and men are affected differently by sexual violence at different ages, and this has significant implications for health promotion programs, and specifically HIV prevention.

Discordant Responses to Potent Antiretroviral Treatment in Previously Naive HIV-1-Infected Adults Initiating Treatment in Resource-Constrained Countries The Antiretroviral Therapy in Low-Income Countries (ART-LINC) Collaboration

Objectives:To assess the frequency of and risk factors for discordant responses at 6 months on highly active antiretroviral therapy (HAART) in previously treatment-naive HIV patients from resource-limited countries. Methods:The Antiretroviral Therapy in Low-Income Countries Collaboration is a network of clinics providing care and treatment to HIV-infected patients in Africa, Latin America, and Asia. Patients who initiated therapy between 1996 and 2004, were aged 16 years or older, and had a baseline CD4 cell count were included in this analysis. Responses were defined based on plasma viral load (PVL) and CD4 cell count at 6 months as complete virologic and immunologic (VR+IR+), virologic only (VR+IR−), immunologic only (VR−IR+), and nonresponse (VR−IR−). Multinomial logistic regression was used to assess the association between therapy responses and clinical and demographic variables. Results:Of the 3111 patients eligible for analysis, 1914 had available information at 6 months of therapy: 1074 (56.1%) were VR+IR+, 364 (19.0%) were VR+IR−, 283 (14.8%) were (VR−IR+), and 193 (10.1%) were VR−IR−. Compared with complete responders, virologic-only responders were older, had a higher baseline CD4 cell count, had a lower baseline PVL, and were more likely to have received a nonstandard HAART regimen; immunologic-only responders were younger, had a lower baseline CD4 cell count, had a higher baseline PVL, and were more likely to have received a protease inhibitor-based regimen. Conclusions:The frequency of and risk factors for discordant responses were comparable to those observed in developed countries. Longer follow-up is needed to assess the long-term impact of discordant responses on mortality in these resource-limited settings.

Extent to which low-level use of antiretroviral treatment could curb the AIDS epidemic in sub-Saharan Africa

BACKGROUND Despite growing international pressure to provide HIV-1 treatment to less-developed countries, potential demographic and epidemiological impacts have yet to be characterised. We modelled the future impact of antiretroviral use in South Africa from 2000 to 2005. METHODS We produced a population projection model that assumed zero antiretroviral use to estimate the future demographic impacts of the HIV-1 epidemic. We also constructed four antiretroviral-adjusted scenarios to estimate the potential effect of antiretroviral use. We modelled total drug cost, cost per life-year gained, and the proportion of per-person health-care expenditure required to finance antiretroviral treatment in each scenario. FINDINGS With no antiretroviral use between 2000 and 2005, there will be about 276,000 cumulative HIV-1-positive births, 2,302,000 cumulative new AIDS cases, and the life expectancy at birth will be 46.6 years by 2005. By contrast, 110,000 HIV-1-positive births could be prevented by short-course antiretroviral prophylaxis, as well as a decline of up to 1 year of life expectancy. The direct drug costs of universal coverage for this intervention would be US