The association of race, sociodemographic, and behavioral characteristics with response to highly active antiretroviral therapy in women

OBJECTIVE: To determine the association of race with clinical and laboratory outcomes after initiation of highly active antiretroviral therapy (HAART) in HIV-1-infected women in the United States. STUDY DESIGN: Prospective cohort study. PARTICIPANTS: A total of 961 HIV-1-infected women participating in the Women's Interagency HIV Study initiating HAART between July 1, 1995 and September 30, 2003. RESULTS: Over a median of 5.1 years of follow-up, in univariate Cox regression analyses, white women were more likely than African American women to attain a virologic response (relative hazard [RH]=1.34, P=0.005), less likely to experience viral rebound (RH=0.76, P=0.051), and less likely to die (RH=0.63, P=0.040). There were no significant differences, however, among racial groups in outcomes after adjustment for pre-HAART CD4, HIV-1 RNA, history of AIDS-defining illness, age, antiretroviral therapy use, baseline HIV-1 exposure category, and post-HAART behavioral and clinical variables associated with poorer response (discontinuation of HAART, lower income, smoking, current drug use, and depression). Continuous HAART use and lack of depression differed by race and were the strongest predictors of favorable outcomes. CONCLUSION: No significant differences by race were found in virologic, immunologic, or clinical outcomes after adjustment for continued HAART use and depression. These findings suggest that strategies to enhance HAART continuation, including assessing pharmacogenetic influences that may result in greater toxicity and discontinuation rates, and treating depression can improve individual and population-based effects of treatment and potentially mitigate racial disparities in AIDS-related outcomes.     

Self-reported adherence to antiretroviral therapy for HIV-1 infection and virologic treatment response: a meta-analysis

BACKGROUND: Adherence to highly active antiretroviral therapy (HAART) for HIV-1 infection is essential for plasma HIV-1 RNA suppression. Self-report is the most frequently used measure of adherence to HAART, but its validity is controversial. Studies on the relation between self-reported adherence and virologic treatment response have shown inconsistent results. We investigated whether this variability between studies about the effect of self-reported adherence on virologic treatment response could be attributed to study design features. METHODS: We searched for studies reporting on adult nonpregnant patients prescribed antiretroviral therapy for chronic HIV-1 infection using a self-reported adherence measure and providing information about the relation between adherence and plasma HIV-1 RNA concentrations. Meta-analysis with random effects modeling was used to pool data and to investigate sources of heterogeneity. RESULTS: Sixty-five studies fulfilled inclusion criteria, containing data from 15,351 patients. The pooled odds ratio (95% confidence interval) of detectable plasma viral load in nonadherent patients was 2.31 (1.99-2.68). There was significant heterogeneity among studies (P < 0.001). Not ascertaining confidentiality of responses, use of actual viral load measurements, an adherence threshold lower than 95%, higher percentages of patients on their initial antiretroviral regimen, and higher percentages of patients with a history of intravenous drug use within a study were associated with higher point estimates. CONCLUSIONS: Overall, we observed that self-reported adherence measures can distinguish between clinically meaningful patterns of medication-taking behavior. Distinct study characteristics were significantly associated with the relation between adherence and virologic response. These characteristics should be taken into consideration when interpreting results from studies on self-reported adherence.     

Surrogate markers for disease progression in treated HIV infection.

OBJECTIVE: To characterize the relationships among highly active antiretroviral therapy (HAART), HIV-1 RNA levels, immune system markers, and clinical outcome in a cohort of HIV-1-infected homosexual men. PATIENTS: A total of 123 men enrolled in the Amsterdam cohort study of HIV-1 infection and AIDS with a documented seroconversion for HIV-1 antibodies and known date of seroconversion were included in this study. METHODS: CD4 + /CD8 + T-cell counts and HIV-1 RNA levels in plasma were measured approximately every 6 months. Dates of starting and stopping antiretroviral therapy were also recorded. The relationship between HIV-1 RNA in plasma, CD4 + /CD8 + T-cell counts and HAART and their influence on clinical outcome were examined using a graphical chain modeling approach. Generalized estimating equations were used to examine correlations among the three disease markers. Hazards models with time-dependent covariates were used to examine the influence of HAART and the disease markers on progression to AIDS. RESULTS: HAART was significantly associated with reduced disease progression (relative hazard [RH] of AIDS, 0.20;, 95% confidence interval [CI], 0.05-0.85). The most recent HIV-1 RNA measurement and CD4 + T-cell count are independently associated with disease progression (adjusted RH for HIV-1 RNA 1.8 per log 10 increase; 95% CI, 1.2-2.6, p =.002; adjusted RH for CD4 + 0.48 per 100 x 10(6)/L increase; 95% CI, 0.40-0.58; p <.001). Depending on these measurements, HAART was no longer significantly associated with AIDS (adjusted RH, 0.81; 95% CI, 0.18-3.6; p =.78). CONCLUSIONS: HIV-1 RNA levels in plasma and CD4 + T-cell counts are currently considered as effective surrogate markers for the effect of HAART on disease progression in this cohort.     

Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission

CONTEXT: The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989. OBJECTIVE: To evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level. DESIGN: Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000. MAIN OUTCOME MEASURE: HIV-1 status of the infant. RESULTS: HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for <400; 5.3% for 400 to 3499; 9.3% for 3500 to 9999; 14.7% for 10,000 to 29,999; and 23.4% for >30,000 copies/mL (p =.0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. CONCLUSION: Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.     

Antiretroviral-associated toxicity among HIV-1-seropositive pregnant women in Mozambique receiving nevirapine-based regimens

OBJECTIVE: To assess toxicities associated with highly active antiretroviral therapy (HAART) among HIV-1-infected pregnant women treated with nevirapine-based regimens according to Mozambican national guidelines. STUDY DESIGN: Prospective cohort study. METHODS: HIV-1-infected antiretroviral-naive pregnant women with CD4 counts < or =350 cells/microL were initiated on nevirapine, lamivudine, and stavudine or zidovudine and followed monthly. Severe hepatotoxicity was defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels > or =5-fold the upper limit of normal. Analyses were stratified by baseline CD4 count (<250 vs. 250-350 cells/microL). RESULTS: Among 146 pregnant women, 75 (52%) began nevirapine, lamivudine, and zidovudine and 71 (48%) began nevirapine, lamivudine, and stavudine. Overall, 79 (54%) women had CD4 counts <250 cells/microL, 7 (5%) had grade II hepatotoxicity, and 4 (3%) had severe (grade III or IV) hepatotoxicity. All 4 women with severe hepatotoxicity had baseline CD4 counts > or =250 cells/microL (P = 0.02). Rates of skin toxicity, anemia, and peripheral neuropathy did not differ by CD4 cell count group. Overall, 12 (8%) women changed or discontinued HAART as a result of drug toxicity. CONCLUSIONS: Severe hepatotoxicity from nevirapine-containing HAART in this cohort of pregnant women was more common at higher CD4 counts (6% vs. 0% among women with CD4 counts > or =250 cells/microL and CD4 counts <250 cells/microL, respectively), suggesting that laboratory monitoring is necessary when administering nevirapine-containing regimens to pregnant women with CD4 counts > or =250 cells/microL.     

Effects of depression and selective serotonin reuptake inhibitor use on adherence to highly active antiretroviral therapy and on clinical outcomes in HIV-infected patients

OBJECTIVES: To determine the impact of depression on highly active antiretroviral therapy (HAART) adherence and clinical measures and investigate if selective serotonin reuptake inhibitors (SSRIs) improve these measures. DESIGN: Retrospective cohort study. METHODS: In 2 large health maintenance organizations, we measured the effects of depression (with and without SSRI use) on adherence and changes in viral and immunologic control among HIV-infected patients starting a new HAART regimen. HAART adherence, HIV RNA levels, and changes in CD4 T-cell counts through 12 months were measured. RESULTS: A total of 3359 patients were evaluated; 42% had a depression diagnosis, and 15% used SSRIs during HAART. Depression without SSRI use was associated with significantly decreased odds of achieving > or =90% adherence to HAART (odds ratio [OR] = 0.81, 95% confidence interval [CI]: 0.70 to 0.98; P = 0.03). Depression was associated with significantly lower odds of an HIV RNA level <500 copies/mL (OR = 0.77, 95% CI: 0.62 to 0.95; P = 0.02). Depressed patients compliant with SSRI medication (>80% adherence to SSRI) had HAART adherence and viral control statistically similar to nondepressed HIV-infected patients taking HAART. Comparing depressed with nondepressed HIV-infected patients, CD4 T-cell responses were statistically similar; among depressed patients, those compliant with SSRI had statistically greater increases in CD4 cell responses. CONCLUSIONS: Depression significantly worsens HAART adherence and HIV viral control. Compliant SSRI use is associated with improved HIV adherence and laboratory parameters.     

Efficacy of interventions in improving highly active antiretroviral therapy adherence and HIV-1 RNA viral load. A meta-analytic review of randomized controlled trials

Adherence to highly active antiretroviral therapy (HAART) is generally suboptimal, limiting the effectiveness of HAART. This meta-analytic review examined whether behavioral interventions addressing HAART adherence are successful in increasing the likelihood of a patient attaining 95% adherence or an undetectable HIV-1 RNA viral load (VL). We searched electronic databases from January 1996 to September 2005, consulted with experts in the field, and hand searched reference sections from relevant articles. Nineteen studies (with a total of 1839 participants) met the selection criteria of describing a randomized controlled trial among adults evaluating a behavioral intervention with HAART adherence or VL as an outcome. Random-effects models indicated that across studies, participants in the intervention arm were more likely than those in the control arm to achieve 95% adherence (odds ratio [OR] = 1.50, 95% confidence interval [CI]: 1.16 to 1.94); the effect was nearly significant for undetectable VL (OR = 1.25; 95% CI: 0.99 to 1.59). The intervention effect for 95% adherence was significantly stronger in studies that used recall periods of 2 weeks or 1 month (vs. 相似文献   

Interruption and discontinuation of highly active antiretroviral therapy in the multicenter AIDS cohort study

OBJECTIVE: Identify the determinants and consequences of interrupting and discontinuing highly active antiretroviral therapy (HAART) among a population-based cohort of HIV-infected men. METHODS: Longitudinal analyses were applied to 2916 person-visit pairs (589 men) of continuous HAART use, 243 person-visit pairs (154 men) during which HAART was interrupted, and 151 person-visit pairs (130 men) in which HAART was discontinued by the second visit. HIV RNA increase was defined as > or =1 log10 copies/mL across the visit pairs. RESULT:: Younger age, black race, geographic location, higher HIV RNA level, depression, shorter time on HAART, lower medication adherence, and not taking a lamivudine-containing regimen predicted interrupting HAART use. Younger age, higher HIV RNA level, depression, and taking an abacavir- or lopinavir-containing regimen predicted discontinuing HAART. Among men with < or =1000 HIV RNA copies/mL, approximately 5% of those who interrupted HAART for < or =7 days and those who continued HAART had an HIV RNA increase. Men with longer interruptions and HAART discontinuers had significantly higher rates of HIV RNA increases (35.7% and 70.5%, respectively). Discontinuation and long interruptions resulted in lower CD4 cell counts. CONCLUSIONS: Host characteristics play a role in short interruptions, whereas longer interruptions may be clinically indicated. These longer stoppages had further virologic and immunologic consequences, however.     

Oral mucosal reactivation rates of herpesviruses among HIV-1 seropositive persons

Herpes simplex virus, cytomegalovirus and Epstein-Barr virus infections are prevalent among HIV-1 infected persons. The relationships between salivary shedding of these herpesviruses have not been characterized. Salivary samples were collected on a median of 61 consecutive days from 41 HIV-1 seropositive persons and tested for HSV-1, HSV-2, CMV and EBV. HSV was detected on 5%, CMV on 19% and EBV on 71% of the days of sampling. HSV shedding was not related to CMV or EBV shedding rates. Persons with EBV shedding rates >40% had CMV DNA detected in their saliva significantly more often than those with EBV shedding rates 200 cells/mm(3) were associated with lower frequency (P=0.02) and quantity (P=0.03) of CMV compared with CD4 counts 相似文献   

Why are baseline HIV RNA levels 100,000 copies/mL or greater associated with mortality after the initiation of antiretroviral therapy?

BACKGROUND: There is conflicting evidence regarding the impact of baseline plasma HIV RNA on virologic responses after the initiation of triple-drug antiretroviral therapy (highly active antiretroviral therapy [HAART]). This has made it difficult to interpret the recently reported association between baseline plasma HIV RNA and mortality. We evaluated whether baseline CD4 cell count and plasma HIV RNA predicted virologic suppression (<500 copies/mL) and rebound (> or =500 copies/mL) among adherent HIV-infected patients. METHODS: Antiretroviral-naive HIV-infected patients were stratified by baseline CD4 cell count, plasma HIV RNA, and adherence level. Cox and logistic regression were used to evaluate the time to suppression and rebound and the odds of ever achieving HIV RNA suppression. RESULTS: A total of 1422 individuals initiated HAART between August 1, 1996 and July 31, 2000 and were followed to March 31, 2002. Adherent patients with HIV RNA levels > or =100,000 copies/mL and 50 to 99,999 copies/mL were slower to suppress HIV RNA than patients with baseline HIV RNA <50,000 copies/mL in Kaplan-Meier analyses. Although the odds of RNA suppression among adherent patients with baseline RNA levels <50,000 copies/mL and 50 to 99,999 copies/mL were similar (P = 0.197), patients with baseline HIV RNA > or =100,000 copies/mL were markedly less likely ever to achieve suppression during follow-up (adjusted odds ratio: 0.27 [95% confidence interval: 0.13-0.54]; P < 0.001). No differences in the rate of virologic rebound were observed between adherent patients in the various baseline HIV RNA strata, and CD4 cell count was not associated with suppression or rebound. CONCLUSIONS: Baseline HIV RNA > or =100,000 copies/mL was associated with a significantly lower likelihood of ever achieving HIV RNA suppression during follow-up. These findings likely explain the association between baseline HIV RNA levels and mortality and have important implications for the development of therapeutic guidelines.     

HIV-1蛋白酶和逆转录酶抗药基因变异检测方法的建立及临床应用

目的 应用现有ＤＮＡ序列分析技术对人类免疫缺陷病毒１型（ＨＩＶ－１）的蛋白酶（ＰＲ）和逆转录酶（ＲＴ）基因进行简便、快速、准确的序列分析,在临床上为ＨＩＶ－１患者治疗方案的确定提供可靠依据。方法 从ＨＩＶ－１感染者血清中提取ＲＮＡ,用套管式逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）扩增ＨＩＶ－１的ＰＲ和ＲＴ基因片段,并对此片段进行核苷酸序列分析。结果 本方法对血清中ＨＩＶ－１ＲＮＡ含量约２０００拷贝／ｍｌ以上的样品都能有效扩增。在序列分析时背景干扰少,对２５％左右的混合序列均能准确反映。通过对临床治疗病人进行动态序列分析观察,发现在药物治疗过程中,病人血浆中ＨＩＶ－１ＲＮＡ含量变化与ＰＲ和ＲＴ基因抗药性变异具有很大相关性。结论 ＰＲ和ＲＴ基因序列分析方法能够及时、准确地反映ＨＩＶ－１患者在抗病毒药物治疗过程中病毒的变     

Adherence to highly active antiretroviral therapy assessed by pharmacy claims predicts survival in HIV-infected South African adults

It is unclear how adherence to highly active antiretroviral therapy (HAART) may best be monitored in large HIV programs in sub-Saharan Africa where it is being scaled up. We aimed to evaluate the association between HAART adherence, as estimated by pharmacy claims, and survival in HIV-1-infected South African adults enrolled in a private-sector AIDS management program. Of the 6288 patients who began HAART between January 1999 and August 2004, 3805 (61%) were female and 6094 (97%) were black African. HAART adherence was >or=80% for 3298 patients (52%) and 100% for 1916 patients (30%). Women were significantly more likely to have adherence>or=80% than men (54% vs 49%, P<0.001). The median (interquartile range) follow-up time was 1.8 (1.37-2.5) years. As of 1 September 2004, 222 patients had died-a crude mortality rate of 3.5%. In a multivariate Cox regression model, adherence<80% was associated with lower survival (relative hazard 3.23; 95% confidence interval: 2.37-4.39). When medication adherence was divided into 5 strata with a width of 20% each, each stratum had lower survival rates than the adjacent, higher-adherence stratum. Among other variables tested, only baseline CD4+ T-cell count was significantly associated with decreased survival in multivariate analysis (relative hazard 5.13; 95% confidence interval: 3.42-7.72, for CD4+ T-cell count200 cells/microL). Pharmacy-based records may be a simple and effective population-level tool for monitoring adherence as HAART programs in Africa are scaled up.     

Field adherence to highly active antiretroviral therapy in HIV-infected adults in Abidjan, Côte d'Ivoire

OBJECTIVES: To estimate adherence to highly active antiretroviral therapy (HAART) and its determinants in HIV-infected adults followed in field conditions in Abidjan. METHODS: A standardized questionnaire was administered to all consecutive adults on HAART who attended 3 urban HIV outpatient clinics. Patients were asked to self-report their pill intake during the previous 7 days, and, when necessary, to explain the reason(s) why they missed at least 1 intake. The adherence rate was estimated as the number of pills actually taken divided by the number of pills that should have been taken. The association of incomplete adherence (adherence rate<90%) with patients' characteristics was studied using multivariate logistic regression. RESULTS: Three hundred eight patients (male/female ratio: 1:1, mean time on HAART: 22 months) were interviewed. The median self-reported adherence rate was 78% (interquartile range: 65%-90%), with 76% of patients considered as incompletely adherent (adherence rate<90%). The most frequent self-reported reasons for missing at least 1 intake were an antiretroviral drug being out of stock in the clinic pharmacy (28%), the fear of drug side effects (27%), the impossibility of paying the drug's price (20%), and the intervention of traditional practitioners (18%). The only variables significantly independently associated with incomplete adherence were a school level>or=secondary (odds ratio [OR]=1.88; P=0.03) and the absence of a patient's long-term formal commitment to adhere to HAART (OR=3.08; P=0.01). CONCLUSIONS: These data illustrate the difficulty in obtaining high levels of adherence in field conditions in Abidjan. Sustainable access to treatment should be promoted by combating access barriers such as running out of drugs and costs that are too high.     

Gender and long-term metabolic toxicities from antiretroviral therapy in HIV-1 infected persons

Gender differences in a large population-based cohort of HIV-1 infected patients (245 women and 723 men) were examined with respect to the incidence of metabolic and morphologic alterations after initiation of highly active antiretroviral therapy (HAART). Patients initiated HAART between January 1996 and December 2003. The outcome measures were the incidence of hyperglycemia, hypercholesterolemia, symptomatic lactic acidosis, treatment-limiting lipodystrophy, and hypersensitivity reaction. Cox proportional hazards models were used to estimate the crude and adjusted hazard ratios of reaching the endpoints for exposures and covariates. Women were younger than men (35 +/- 9.8 vs. 40 +/- 8.2 years, P < 0.001) and more frequently from Haiti or Africa (59%), whereas 76% of men were Canadian-born. Type of initial HAART regimen did not differ between women and men. There were no gender differences in the overall incidence of hyperglycemia, hypercholesterolemia, or treatment-limiting lipodystrophy, even after adjusting for age, CD4 cell count, viral load, time since HIV diagnosis, history of AIDS-defining illness and year of HAART initiation. In contrast, women had significantly higher risk of developing lactic acidosis than men (P = 0.0009). Hypersensitivity reactions were also more frequent in women than men (adjusted hazard ratio = 4.4 (95% CI: 2.1-9.3)). Collectively, these data suggest that metabolic toxicities after HAART do not differ by gender but that lactic acidosis and hypersensitivity reactions are more frequent in women than men.     

A once-daily lopinavir/ritonavir-based regimen provides noninferior antiviral activity compared with a twice-daily regimen

OBJECTIVE: To evaluate the safety and noninferiority and to explore the efficacy of administration of once-daily versus twice-daily lopinavir/ritonavir (LPV/r) in antiretroviral-naive HIV-1-infected subjects. DESIGN: Randomized, open-label, multicenter, comparative study. METHODS: One hundred ninety antiretroviral-naive subjects with plasma HIV-1 RNA level >1000 copies/mL and any CD4 cell count were randomized to lopinavir/ritonavir at a dose of 800/200 mg administered once daily (n = 115) or lopinavir/ritonavir at a dose of 400/100 mg administered twice daily (n = 75). Subjects also received tenofovir disoproxil fumarate (TDF) at a dose of 300 mg and emtricitabine (FTC) at a dose of 200 mg administered once daily. RESULTS: The median baseline plasma HIV-1 RNA level and CD4 count were 4.8 log10 copies/mL and 216 cells/mm, respectively. Before week 48, 20% (once daily) and 29% (twice daily) subjects discontinued. Virologic responses of the subjects through 48 weeks were comparable; 70% (once daily) and 64% (twice daily) achieved an HIV-1 RNA level <50 copies/mL by intent-to-treat, noncompleter = failure analysis. No subject demonstrated LPV or TDF resistance, but 3 subjects (2 in the once-daily group, 1 in the twice-daily group) demonstrated FTC resistance. Mean increases in CD4 count were similar. Diarrhea (16% in the once-daily group, 5% in the twice-daily group; P = 0.036) was the most common moderate or severe study drug-related adverse event. CONCLUSIONS: Through 48 weeks, a once-daily regimen of lopinavir/ritonavir + TDF + FTC appears to have similar virologic and immunologic responses in antiretroviral-naive subjects as the same regimen with lopinavir/ritonavir administered twice daily. Both regimens were relatively well tolerated, and no LPV or TDF resistance was observed.     

Randomized control trial of peer-delivered, modified directly observed therapy for HAART in Mozambique

OBJECTIVE: To assess the efficacy of a peer-delivered intervention to promote short-term (6-month) and long-term (12-month) adherence to HAART in a Mozambican clinic population. DESIGN: A 2-arm randomized controlled trial was conducted between October 2004 and June 2006. PARTICIPANTS: Of 350 men and women (> or = 18 years) initiating HAART, 53.7% were female, and 97% were on 1 fixed-dose combination pill twice a day. INTERVENTION: Participants were randomly assigned to receive 6 weeks (Monday through Friday; 30 daily visits) of peer-delivered, modified directly observed therapy (mDOT) or standard care. Peers provided education about treatment and adherence and sought to identify and mitigate adherence barriers. OUTCOME: Participants' self-reported medication adherence was assessed 6 months and 12 months after starting HAART. Adherence was defined as the proportion of prescribed doses taken over the previous 7 days. Statistical analyses were performed using intention-to-treat (missing = failure). RESULTS: Intervention participants, compared to those in standard care, showed significantly higher mean medication adherence at 6 months (92.7% vs. 84.9%, difference 7.8, 95% confidence interval [CI]: 0.0.02, 13.0) and 12 months (94.4% vs. 87.7%, difference 6.8, 95% CI: 0.9, 12.9). There were no between-arm differences in chart-abstracted CD4 counts. CONCLUSIONS: A peer-delivered mDOT program may be an effective strategy to promote long-term adherence among persons initiating HAART in resource-poor settings.     

Virologic and immunologic response to highly active antiretroviral therapy in indigenous and nonindigenous HIV-1-infected patients in the Netherlands

OBJECTIVE: To compare the results of antiretroviral treatment (highly active antiretroviral therapy [HAART]) in indigenous Dutch (ID) and nonindigenous HIV-1-infected patients in Amsterdam, the Netherlands. We focused on the largest groups of nonindigenous people visiting our outpatient clinic: patients from other industrialized countries (western), from Surinam/Netherlands Antilles (SNA), and from sub-Saharan Africa (SSA). DESIGN: Retrospective cohort analysis of 692 therapy-naive HIV-1-positive individuals who visited our outpatient clinic for the first time between July 1, 1996 and December 31, 2001. METHODS: We compared the groups at the time of their first visit to our clinic; at the start of HAART; and according to the virological, immunologic, and clinical treatment response during the 96 weeks after the start of HAART. RESULTS: Of the patients starting antiretroviral therapy, 362 were ID, 84 were western, 72 were from SNA, and 110 were from SSA. SNA and SSA patients had a lower CD4 cell count at first visit (ID = 330 cells/mm(3), western = 330 cells/mm(3), SNA = 250 cells/mm(3), and SSA = 170 cells/mm(3); P = 0.0002). Treatment in SNA and SSA patients was also started at a lower CD4 cell count, but the plasma HIV-1 RNA level was comparable. After the start of HAART, a similar rise in CD4 cell count was seen in the 4 groups (P = 0.33), but the baseline difference in CD4 cell count remained present during the follow-up period of 96 weeks. After adjusting for variables potentially influencing treatment outcome, the proportion of patients not reaching a plasma HIV-1 RNA level <400 copies/mL was not different for the 4 groups in contrast to the percentage not reaching a plasma HIV-1 RNA level <50 copies/mL (at 48 weeks: ID = 4.8%, western = 27.5%, SNA = 23.1%, and SSA = 24.2%; P = 0.017 over the 96-week time period). After the start of HAART, nonindigenous patients also more often had progression to Centers for Disease Control and Prevention (CDC) stage C or died (P = 0.006). CONCLUSIONS: In nonindigenous patients, treatment with HAART was equally successful in terms of the increase in CD4 cell count but was substantially less effective in achieving a plasma HIV-1 RNA level below 50 copies/mL. Further investigations should explore differences in adherence and pharmacokinetics in these patient groups.