Start Highly Active Antiretroviral Therapy Research Articles

Cluster of differentiation and renal assessment of reactive HIV subjects in Akure Nigeria

Background: HIV/AIDS is a rapidly growing epidemic in sub-Saharan Africa, Nigeria in particular. The report of the 2012 National Reproductive Health Survey Plus indicated that the prevalence of HIV/AIDS in Nigeria, that is, Nigerians currently living with HIV/AIDS is about 3.4% while Ondo State has a prevalence of 4.3%. HIV is a retrovirus that primarily infects components of the human immune system such as CD4 T-cells, macrophages and dendritic cells. Objectives: To evaluate the CD4+ T cell count, sodium, potassium, urea and creatinine in adult HIV seropositive subjects on Highly Active Antiretroviral Therapy (HAART) and those yet to be started on HAART as well as HIV seronegative control subjects. Materials and Methods: Serum levels of CD4+ count of adult HIV seropositive subjects on HAART, yet to start HAART and seronegative controls were determined using flow cytometry while their serum sodium, potassium, urea and creatinine were determined using enzymatic spectrophotometric method. All data were expressed as Mean ± Standard Deviation (SD) and analysed with Analysis of Variance (ANOVA) while multiple comparisons were done using Post Hoc test. Results: The serum sodium is significantly lower in the subjects in HAART group as compared with that of the other two groups. No significant difference in urea & creatinine was found in the three groups. Conclusion: Despite the fact that it appears the drugs did not have adverse effect on the kidneys, there is need for close monitoring of patients on antiretroviral medications as various drugs over time have adverse effects on various organs.

Cost-effectiveness analysis of antiretroviral therapy in a cohort of HIV-infected patients starting first-line highly active antiretroviral therapy during 6 years of observation.

ObjectivesCosts may play a role in deciding how and when to start highly active antiretroviral therapy (HAART) in a naïve patient. The aim of the present study was to assess the cost- effectiveness of treatment with HAART in a large clinical cohort of naïve adults to determine the potential role of single-tablet regimens in the management of patients with human immunodeficiency virus (HIV). An incremental cost-effectiveness ratio analysis was performed, including a quality-adjusted life year approach.ResultsIn total, 741 patients (females comprising 25.5%) were retrospectively included. The mean age was 39 years, the mean CD4 cell count was 266 cells/μL, and the mean viral load was 192,821 copies/mL. The most commonly used backbone was tenofovir + emtricitabine (77.6%); zidovudine + lamivudine was used in 10%, lamivudine + abacavir in 3%, and other nucleoside reverse transcriptase inhibitor (NRTI) or NRTI-free regimens in 9.4% of patients. NNRTIs were used in 52.8% of cases, boosted protease inhibitors in 44.1%, and unboosted protease inhibitors and integrase inhibitors in 0.7% and 2.4%, respectively. Starting therapy at CD4 >500 cells/μL and CD4 351–500 cells/μL rather than at <201 cells/μL was the more cost-effective approach. The same consideration was not true comparing current indications with the possibility to start HAART at any CD4 value (eg, >500 cells per μL); in this case, the incremental cost-effectiveness ratio value was €199,130 per quality-adjusted life year gained, a higher value than the one suggested in guidelines. The single-tablet regimen (STR) invariably dominated any other therapeutic approach. Sensitivity analysis was performed, and starting right away with an STR was cost-effective even when compared with therapeutic strategies contemplating STR as simplification.ConclusionBy integrating clinical data with economic variables, our study offers an estimate of the cost-effectiveness of the various first-line treatment strategies for patients infected with HIV and provides significant evidence to be used in future prospective pharmacoeconomic evaluations.

Immunological and Virological Outcomes at 5 Years in HIV Infected Adults Who Start HAART at a CD4 Cell Count of Less Than 200 in Barbados

Objective: To assess the immunologic and virological response after 5 years of highly active antiretroviral therapy (HAART) in treatment naive HIV-1 infected adults presenting late in the course of their disease. Design: Prospective long term observational study. The response to HAART is described in HIV-1 infected ARV naive adults initiating treatment at CD4+ cell counts < 200 during June 2005 through December 2005 in Barbados, West Indies. Baseline values as well as 5 years post-HAART values for CD4+ cell counts and viral load were recorded for the cohort. Results: 50 ARV naive HIV-1 infected adults initiated treatment when their CD4+ cell count was, 200. Most received Combivir plus Nevirapine or Efavirenz. At the baseline, their median CD4+count was 36 cells/μL (IQ Range:15-82) and their median viral load was at 75,000 (4.87 log10) with an IQ Range of 52,700-226,000. After 5 years of therapy, the median increase in the CD4+ cell count was 122 cell/μL (IQ Range, 45-185). Twenty three (46%) patients had achieved CD4+ cell counts of >200 cells/μL. 36 (72%) patients had an undetectable viral load (<50 copies/mL). The median decline in viral load at 5 years of therapy was 74,950 (4.87 log10) copies/mL with an IQ Range of 52,700 -226,000. Conclusion: In this relatively small cohort of treatment naive patients presenting late in the course of HIV disease, there was good immunological and virological response after 5 years of initiating HAART irrespective of their baseline CD4+ counts and viral load, age or gender.

Effect of antiretroviral therapy on survival of HIV/TB-infected patients in Ukraine

Introduction: There is little information from Ukraine about the effect of highly active antiretroviral therapy (HAART) on survival of HIV/ TB-infected patients. We evaluated the survival and the effect of HAART on mortality on these patients. Methods: Prospective cohort study of HIV patients who developed TB from January 2005 to December 2006 in a Zaporizhzhya AIDS Center, and were tracked for 60 months after start HAART. Survival was determined by Kaplan-Meier method and effect of HAART on survival was evaluated using Cox proportional hazards models. Results: Eighty patients were studied (mean age 34 years, 50% male, median CD4 count 103 cell/μL). In 60 months of HAART 14 patients died. The probability of survival was 82%. In multivariate analysis, patients with a CD4 cell count <100 μL had a 5-fold higher risk of mortality (HR 5, 2; 95% CI 1.4-19, 4) and those with extra pulmonary tuberculosis a 2, 2-fold increased risk (HR 2, 2, 95% CI 1, 1-8, 3). Conclusions: HAART significantly increased probability of survival and reduced the risk of death for HIV/TB-infected patients in Ukraine.

Linking women who test HIV‐positive in pregnancy‐related services to long‐term HIV care and treatment services: a systematic review

To quantify attrition between women testing HIV-positive in pregnancy-related services and accessing long-term HIV care and treatment services in low- or middle-income countries and to explore the reasons underlying client drop-out by synthesising current literature on this topic. A systematic search in Medline, EMBASE, Global Health and the International Bibliography of the Social Sciences of literature published 2000-2010. Only studies meeting pre-defined quality criteria were included. Of 2543 articles retrieved, 20 met the inclusion criteria. Sixteen (80%) drew on data from sub-Saharan Africa. The pathway between testing HIV-positive in pregnancy-related services and accessing long-term HIV-related services is complex, and attrition was usually high. There was a failure to initiate highly active antiretroviral therapy (HAART) among 38-88% of known-eligible women. Providing 'family-focused care', and integrating CD4 testing and HAART provision into prevention of mother-to-child HIV transmission services appear promising for increasing women's uptake of HIV-related services. Individual-level factors that need to be addressed include financial constraints and fear of stigma. Too few women negotiate the many steps between testing HIV-positive in pregnancy-related services and accessing HIV-related services for themselves. Recent efforts to stem patient drop-out, such as the MTCT-Plus Initiative, hold promise. Addressing barriers and enabling factors both within health facilities and at the levels of the individual woman, her family and society will be essential to improve the uptake of services.

Dietary Intervention Prevents Dyslipidemia Associated With Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus Type 1–Infected Individuals: A Randomized Trial

The purpose of this study was to evaluate the efficacy of dietary intervention on blood lipids of human immunodeficiency virus (HIV)-1-infected patients who are started on highly active antiretroviral therapy (HAART). Current guidelines recommend diet as first-step intervention for HIV-1-infected individuals with HAART-related dyslipidemia, but there is no evidence from randomized trials to support this recommendation. Eighty-three HIV-1-infected patients, naive from HAART, were randomly assigned to HAART with dietary intervention (diet group, n = 43) or HAART without dietary intervention (control group, n = 40) for 12 months. Diet, according to the National Cholesterol Education Program, was given every 3 months. Before and after intervention, 24-h food records and lipid profile were obtained. Data were analyzed by intention to treat, using mixed-effects models. Diet resulted in reduction of percentage of fat intake (from 31 ± 7% to 21 ± 3% of calories), while controls presented no change in percentage of fat intake. Plasma cholesterol (from 151 ± 29 mg/dl to 190 ± 33 mg/dl) and low-density lipoprotein cholesterol (from 85 ± 24 mg/dl to 106 ± 31 mg/dl) increased in the control group and were unchanged in the diet group. Plasma triglycerides were reduced by diet (from 135 ± 67 mg/dl to 101 ± 42 mg/dl) and increased in the control group (from 134 ± 70 mg/dl to 160 ± 76 mg/dl). After 1-year follow-up, 21% of patients who received diet had lipid profile compatible with dyslipidemia compared with 68% (p < 0.001) of controls. Among HIV-1-positive individuals naive of previous treatment, diet prevents dyslipidemia associated with HAART. (Effect of Nutritional Intervention on the Lipid Profile of HIV-Positive Patients Who Start HAART: a Randomized Trial; NCT00429845).

Disparities in Antiretroviral Treatment: A Comparison of Behaviorally HIV-Infected Youth and Adults in the HIV Research Network

Increasing numbers of youth are becoming HIV-infected and need highly active antiretroviral therapy (HAART). We hypothesized that behaviorally HIV-infected youth (BIY) ages 18 to 24 years are less likely than adults (25 years or older) to receive HAART and, once initiated, more likely to discontinue their first HAART regimen. Longitudinal analysis of treatment-naïve patients (age 18 years or older) meeting criteria for HAART and followed at HIV Research Network sites (2002-2008). Time from meeting criteria to HAART initiation and duration on first regimen were assessed using Cox proportional hazards regression. A total of 3127 (268 youth, 2859 adult) treatment-naïve, HIV-infected patients met criteria. BIY were more likely to be black (66.8% vs 51.1%; P < 0.01) and less likely to identify injection drug use HIV risk (1.1% vs 8.8%; P < 0.01) than adults 25 years of age or older. Nearly 69% of BIY started HAART versus 79% of adults (P < 0.001). Adults 25 to 29 years of age (adjusted hazards ratio [AHR], 1.39; 95% confidence interval [CI], 1.12-1.73) and 50 years of age or older (AHR, 1.24; 95% CI, 1.00-1.54), but not 30 to 49 years (AHR, 1.19; 95% CI, 0.99-1.44) were more likely to initiate HAART than BIY. Attending four or more HIV provider visits within 1 year of meeting criteria was associated with HAART initiation (AHR, 1.91; 1.70-2.14). CD4 200 to 350 versus less than 200 cells/mm (AHR, 0.57; 95% CI, 0.52-0.63), and injection drug use (AHR, 0.80; 95% CI, 0.69-0.92) were associated with a lower likelihood of HAART initiation. There were no age-related differences in duration of the first regimen. BIY are less likely to start HAART when meeting treatment criteria. Addressing factors associated with this disparity is critical to improving care for youth.

Presentation of HIV-associated nephropathy and outcome in HAART-treated patients

Among the numerous renal diseases observed in human immunodeficiency virus (HIV) patients, HIV-associated nephropathy (HIVAN) is a major cause of end-stage renal disease (ESRD). The purpose of our study was to describe the presentation and outcome of HIVAN in the era of highly active antiretroviral therapy (HAART). We analysed clinical features and outcome of 57 patients with histologically proven HIVAN diagnosed between 2000 and 2009 in four teaching hospitals in Paris, France. This series was characterized by median age of 41 years (18-58), frequent African origin (87%), severe renal dysfunction [estimated glomerular filtration rate (eGFR) 20 mL/min/1.73m(2) (1-68)], high-grade proteinuria [4.1 g/day (0.6-16.8)], high proportion of sclerotic glomeruli [31.5% (0-95)], high HIV load [4.5 log copies/mL (0-6.7)] and low CD4+ count [127/mm(3) (3-713)]. Nevertheless, a non-negligible proportion of patients did not present with these typical features. Follow-up data were available for 51 patients. ESRD occurred in 30 patients (58.8%). Median renal survival was 40 months. Baseline characteristics significantly associated with ESRD were as follows: severity of renal dysfunction, percentage of sclerotic glomeruli, time from HIV infection to HIVAN diagnosis longer than 1 year and prior exposure to antiretroviral drugs. There was an insignificant trend towards better renal outcome being associated with viral suppression during follow-up. Use of renin-angiotensin system (RAS) blockers was associated with higher renal survival (P < 0.05). Despite HAART, HIVAN led to ESRD in more than half of the cases. Early recognition of the disease is crucial to start HAART and RAS blockers before irreversible renal injury.

Effect of anemia on hepatotoxicity of HAART in HIV patients in Benin city

Background:Hepatotoxicity is a relevant adverse effect of highly active antiretroviral Treatment owing to its frequency, and it can cause interruption of therapy, hepatitis, and death. There is dearth of information on hepatotoxicity arising from highly active antiretroviral therapy (HAART) in anemic patients. Anemia is the most common symptom in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. We studied the effect of anemia on hepatotoxicity in HIV patients who were about to start HAART, attending clinic, or in the medical wards.Materials and Methods:This was a prospective study in which patients were recruited consecutively and followed up for 24 weeks.Results:In all, 84 patients were recruited and 42 were enrolled as controls. The mean ages of the cases and controls were 35.2±9.9 and 35.5±9.0 years, respectively. The age range of the cases was 18-68 years with a median age of 31.5 years, whereas the mean age of the controls was 20-57 years with a median age of 33.5 years. There was no difference (t=0.197, df=124, and P=0.844). There were 61 females (72.6%) and 23 males (27.4%) in the cases, whereas in the controls, there were 34 females (81.0%) and 8 males (19.0%). Among the cases, 30 (35.7%) were anemic, while 54 (64.3%) were not anemic. Six (20%) of the anemic patients had hepatotoxicity, and 9 (16.7%) of the patients with normal packed cell volume had hepatotoxicity. Among the controls, all 42 (100%) patients had normal packed cell volume. Four (9.5%) of the patients had hepatotoxicity. There was no association between hepatotoxicity and anemia (χ2 =3.243, df=2, P=0.198).Conclusion:Anemia did not affect hepatotoxicity of HAART in this study.

Progressive human immunodeficiency virus-associated vasculopathy: time to revise antiretroviral therapy guidelines?

Cardiovascular abnormalities were appreciated early in the epidemic of the acquired immunodeficiency syndrome (AIDS), even before the aetiological agent, human immunodeficiency virus (HIV) was isolated and characterised. The aetiology and pathogenesis of cardiovascular disease in HIV infection is still the subject of intense speculation, and is likely multi-factorial. HIV affects every aspect of the cardiac axis, causing pericarditis, myocarditis, cardiomyopathy, coronary artery disease and microvascular dysfunction, valvular heart disease, pulmonary vascular disease and pulmonary hypertension, stroke and peripheral vascular disease. HIV-associated vasculopathy is an increasingly recognised clinical entity, causing high morbidity and increasing mortality in southern Africa, particularly from stroke and cardiovascular disease. HIV causes disease of the vascular tree, either by a direct effect on vascular or perivascular tissue, or indirectly via immune complex-mediated mechanisms, associated opportunistic infections and malignancies. As a result, highly active antiretroviral therapy (HAART) may have an important role in controlling disease progression. We report a case of histologically defined primary HIV vasculopathy in which the chance to start HAART was initially missed and in which the patient progressed to require bilateral amputations, but obtained disease quiescence upon commencement of HAART.

Long-term clinical and surrogate marker effects of subcutaneous intermittent interleukin-2 without antiretroviral therapy in HIV-infected patients

Subcutaneous administration of interleukin-2 (IL-2) has been shown to increase CD4 counts in HIV-infected patients. It remains unclear whether this effect is associated with a clinical benefit. We conducted a long-term follow-up in the cohort of the UK-Vanguard study in which three groups of 12 antiretroviral-naive subjects with CD4 cell counts >350 cells/mm(3) received no treatment or IL-2 at either 4.5 or 7.5 MIU twice daily in 5 day cycles, respectively. Mean follow-up was 376 weeks. IL-2 therapy was associated with a higher area under the curve of CD4 cell count change from baseline at week 48 but not thereafter. HIV-RNA levels were unaffected. Highly active antiretroviral therapy (HAART) was initiated after a mean of 172, 175 and 152 weeks in the control group, low-dose and high-dose IL-2 treatment group, respectively, a statistically non-significant difference. There was a tendency to start HAART soon after discontinuation of IL-2 therapy which may have been triggered by the steep decay of CD4 counts. There were two serious adverse events in the control group, seven in the low-dose IL-2 group and eight in the high-dose IL-2 group. No pattern of disease was detected, making an association with IL-2 therapy unlikely. We could detect neither a benefit of IL-2 therapy after week 48 nor delayed initiation of HAART. This is currently the longest follow-up data comparing IL-2 therapy with no therapy in antiretroviral-naive HIV-infected patients and does not show a persistent benefit of the intervention.

Determinants of HIV Progression and Assessment of the Optimal Time to Initiate Highly Active Antiretroviral Therapy

We analyze the factors related to progression to AIDS or death in HIV-infected patients from the Proyecto para la Informatización del Seguimiento Clínico epidemiológico de los pacientes con Infección por VIH/SIDA (PISCIS) Cohort and we assess the optimal time to initiate highly active antiretroviral therapy (HAART) taking lead time into account. We selected naive patients who were AIDS-free and initiated HAART after January 1998. Statistical analyses were performed using Cox proportional hazards models. Lead time was defined as the time it took the deferred group with an early disease stage to reach the later stage. The analysis accounting for lead time was performed using multiple imputation methods based on estimates from the pre-HAART period as described elsewhere. Multivariate analysis on 2035 patients (median follow-up = 34.3 months) showed significantly higher hazard ratios (HRs) for a CD4 count <200 cells/microL (HR = 3.79, 95% confidence interval [CI]: 2.18 to 6.57), HIV-1 RNA level >100,000 copies/mL (HR = 1.84, 95% CI: 1.26 to 2.69), and hepatitis C virus (HCV) coinfection (HR = 2.40, 95% CI: 1.65 to 3.49), whereas a lower risk was found for those who started HAART between January 2001 and June 2004 (HR = 0.55, 95% CI: 0.30 to 0.90). When lead time and unseen events were included, we found a higher risk of progression to AIDS among patients who deferred treatment when the CD4 count reached <200 cells/microL (HR = 2.97, 95% CI: 1.91 to 4.63) and 200 to 350 cells/microL (HR = 1.85, 95% CI: 1.03 to 3.33) compared with those who started treatment with CD4 counts from 200 to 350 cells/microL and >350 cells/microL, respectively. Advanced HIV disease, HCV coinfection, and early HAART period were determinants of AIDS progression or death. Lead-time analysis in asymptomatic HIV-infected patients suggests that the best time to start HAART is before the CD4 count falls to lower than 350 cells/microL.

CD4+ Cell Count 6 Years after Commencement of Highly Active Antiretroviral Therapy in Persons with Sustained Virologic Suppression

Sustained suppression of the human immunodeficiency virus (HIV) type 1 RNA load with the use of highly active antiretroviral therapy (HAART) results in immunologic improvement, but it is not clear whether the CD4(+) cell count increases to normal levels or whether it reaches a less-than-normal plateau. We characterized the increase in the CD4(+) cell count in patients in clinical practice who maintained sustained viral suppression for up to 6 years. All patients were from the Johns Hopkins HIV Clinical Cohort, a longitudinal observational study of patients receiving primary HIV care in Baltimore, Maryland, who were observed for >1 year while receiving HAART and who had sustained suppression of the HIV RNA load at <400 copies/mL. We analyzed annual change in the CD4(+) cell count for up to 6 years after the start of HAART, stratified by baseline CD4(+) cell counts of < or =200, 201-350, >350 cells/microL, and we assessed the development of clinical events (death and new acquired immunodeficiency syndrome-defining illness) by Kaplan-Meier analysis. A total of 655 patients were observed for a median of 46 months (range, 13-72 months). The median change from baseline to most recent CD4(+) cell count was +274 cells/microL, with 92% of patients having an increase in CD4(+) cell count. By 6 years, the median CD4(+) cell count was 493 cells/microL among patients with baseline CD4(+) cell counts < or =200 cells/microL, 508 cells/microL among those with baseline CD4(+) cell counts of 201-350 cells/microL, and 829 cells/microL among those with baseline CD4(+) cell counts >350 cells/microL. In addition to baseline CD4(+) cell count, injection drug use and older age were associated with a lesser CD4(+) cell count response, and duration of therapy was associated with a greater CD4(+) cell count response. Only patients with baseline CD4(+) cell counts >350 cells/microL returned to nearly normal CD4(+) cell counts after 6 years of follow-up. Significant increases were observed in all CD4(+) cell count strata during the first year, but there was a lower plateau CD4(+) cell count at lower baseline CD4(+) cell strata. These data suggest that waiting to start HAART at lower CD4(+) cell counts will result in the CD4(+) cell count not returning to normal levels.

Effects of highly active antiretroviral therapy (HAART) on psychomotor performance in children with HIV disease

This study assesses the effects of HAART on psychomotor performance of symptomatic HIV-infected children. It is one of the first studies to look at neurobehavioral functioning in children infected with HIV in resource-limited countries. A longitudinal pilot study of vertically HIV-infected children at the HIV Netherlands Australia Thailand Research Collaboration Center in Bangkok, Thailand. A total of 34 children participated in the study of whom 16 had never received antiretroviral (ARV) therapy and were about to start HAART (Newly treated children), 7 did not receive antiretroviral therapy (Untreated children) and 11 had been treated with HAART for more than one year (HAART experienced children). All children were administered 4 psychomotor tasks at baseline and after 4 months. The Newly treated and the Untreated children were also evaluated after 12 months. In general, the children performed similarly on all psychomotor tasks at baseline. After 12 months of HAART, there was a significant increase in CD4% in the Newly treated group. Overall, psychomotor performance did not change at the 4-month evaluation in all groups. At the 12-month evaluation psychomotor performance had deteriorated substantially on all tasks in both the Newly treated and the Untreated children. There was no significant difference in psychomotor functioning between children newly treated, previously treated and untreated with HAART over the course of one year. Psychomotor performance deteriorated after 12 months of HAART, which provides important indications concerning the lack of benefits of HAART on psychomotor functions in children despite immunologic reconstitution. Further research with larger sample sizes is needed to confirm these findings.

First national guidelines will help better control HIV/AIDS in China

获得的免疫不全症候群(爱滋病)首先在 1981 的夏天在 UnitedStates 被认出，当 US 疾病控制和预防中心( CDC )在 5 种情况和 Kaposi 中报导了 Pneumocystis carinii 肺病( PCP )的 unexplained 出现时“在在洛杉机和纽约的 previouly 健康的同性恋人的 26 种情况中的 s 肉瘤。在月以内，疾病变得在血或 IDV 输送的接受者并且在 hemophiliacs 在男、女的静脉内的药用户(IDU ) 并且此后不久认出了。

Patients’ Preferences regarding the Timing of Highly Active Antiretroviral Therapy Initiation for Chronic Asymptomatic HIV-1 Infection

In patients with a chronic asymptomatic HIV-1 infection and >200 CD4+ T-cells/microl, the optimal timing of highly active antiretroviral therapy (HAART) initiation is unclear. It involves a trade-off between a potentially reduced risk of mortality, when started earlier in the course of infection, and an earlier exposure to pill burden and potential toxicities. We investigated patients' preferences for immediate HAART initiation relative to delaying HAART for 1 year. Consecutive patients were asked for their preference during an interview. A hypothetical difference in 3-year mortality risk between both options was systematically varied between 0% and 10% to determine the threshold at which preference would switch to HAART initiation. About 30% of patients preferred HAART initiation even if the mortality risk would be equal for both options. Almost 25% always preferred delaying HAART even if this would result in a 10% greater mortality risk. Most treatment guidelines recommend delaying HAART >350 CD4+ T-cells/microl. However, at a risk difference between starting and delaying HAART that corresponds with this CD4+ T-cell count, about 50% would prefer to start HAART immediately. Most guidelines recommend starting HAART below 200 CD4+ T-cells/microl. However, at a risk difference between both options corresponding with this CD4+ T-cell count, about 40% preferred delaying HAART. We found large variation in patients' preferences. Some patients were more inclined to initiate HAART earlier than the recommended guidelines, whereas others were more inclined to delay HAART. These findings emphasize the need for shared decision-making when deciding on the most optimal timing of HAART initiation in chronic asymptomatic HIV-1 infection.

Can highly active antiretroviral therapy reduce the spread of HIV?: A study in a township of South Africa.

Calls have been made for the large-scale delivery of highly active antiretroviral therapy (HAART) to people infected with HIV in developing countries. If this is to be done, estimates of the number of people who currently require HAART in high HIV prevalence areas of sub-Saharan Africa are needed, and the impact of the widespread use of HAART on the transmission and, hence, spread of HIV must be assessed. To estimate the proportion of people eligible for combination antiretroviral therapy and to evaluate the potential impact of providing HAART on the spread of HIV-1 under World Health Organization (WHO) guidelines in a South African township with a high prevalence of HIV-1. A community-based cross-sectional study in a township near Johannesburg, South Africa, of a random sample of approximately 1000 men and women aged 15 to 49 years. Background characteristics and sexual behavior were recorded by questionnaire. Participants were tested for HIV-1, and their CD4 cell counts and plasma HIV-1 RNA loads were measured. The proportion of people whose CD4 cell count was less than 200 cells/mm and who would be eligible to receive HAART under WHO guidelines was estimated. The potential impact of antiretroviral drugs on the spread of HIV-1 in this setting was determined by estimating among the partnerships engaged in by HIV-1-positive individuals the proportion of spousal and nonspousal partnerships eligible to receive HAART and then by calculating the potential impact of HAART on the annual risk of HIV-1 transmission due to sexual contacts with HIV-1-infected persons. The results were compared with those obtained using United States Department of Health and Human Services (USDHHS) guidelines. The overall prevalence of HIV-1 infection was 21.8% (19.2%-24.6%), and of these people, 9.5% (6.1%-14.9%) or 2.1% (1.3%-3.3%) of all those aged 15 to 49 years would be eligible for HAART (ranges are 95% confidence limits). In each of the next 3 years 6.3% (4.6%-8.4%) of those currently infected with HIV-1 need to start HAART. Among the partnerships in which individuals were HIV-1-positive, only a small proportion of spousal partnerships (7.6% [3.4%-15.6%]) and nonspousal partnerships (5.7%, [3.0%-10.2%]) involved a partner with a CD4 cell count below 200 cells/mm and would have benefited from the reduction of transmission due to the decrease in plasma HIV-1 RNA load under HAART. Estimates of the impact of HAART on the annual risk of HIV-1 transmission show that this risk would be reduced by 11.9% (7.1%-17.0%). When using USDHHS guidelines, the proportion of HIV-1-positive individuals eligible for HAART reached 56.3% (49.1%-63.2%) and the impact of HAART on the annual risk of HIV-1 transmission reached 71.8% (64.5%-77.5%). The population impact of HAART on reducing sexual transmission of HIV-1 is likely to be small under WHO guidelines, and reducing the spread of HIV-1 will depend on further strengthening of conventional prevention efforts. A much higher impact of HAART is to be expected if USDHHS guidelines are used.

Mortality and progression to AIDS after starting highly active antiretroviral therapy.

To examine survival and progression to AIDS among HIV-infected patients after starting highly active antiretroviral therapy (HAART). The study population consisted of 3724 patients from the ATHENA observational cohort who initiated HAART. We considered progression to either an AIDS-defining disease or death, distinguishing HIV-related and non-related (including therapy-related) deaths. A time-dependent multivariate hazards model was fitted to the patient data and 5-year survival probabilities under various therapy scenarios estimated. A total of 459 patients developed AIDS and 346 died during 12 503 person-years of follow-up. HIV-related mortality decreased from 3.8 to 0.7 per 100 person-years between 1996 and 2000 whereas non-HIV-related mortality did not change (0.4 and 0.9, respectively, P = 0.25). For asymptomatic and symptomatic therapy naive patients younger than 50 years with CD4 counts above 10 x 10(6) and 150 x 10(6) cells/l, respectively, predicted 5-year survival probabilities were above 90% when HAART was used continuously. This limit was 450 x 10(6) cells/l when HAART was used during 20 weeks in each 24 week-period of follow-up, and 110 x 10(6) cells/l when patients delayed initiation of HAART for 1 year after becoming eligible for treatment. Survival probabilities were high among HIV-infected patients initiating HAART at an early stage of infection. The best therapy strategy is therefore to start HAART at this stage of infection. However, deferring HAART in patients with high CD4 cell counts may be clinically more appropriate given toxicity and adherence problems. The lack of any change in non-HIV-related mortality suggests that toxicity has not yet become a major risk factor for death.

A Comparison of Exposure Groups in the EuroSIDA Study: Starting Highly Active Antiretroviral Therapy (HAART), Response to HAART, and Survival

Background: Concerns have been raised that intravenous drug users may be less likely to start highly active antiretroviral therapy (HAART) and that adherence to therapy may be poor among this group of patients. Given the decreased mortality and incidence of AIDS-defining illnesses among patients with HIV who start HAART, this may lead to a poorer prognosis among intravenous drug users. Purpose: To compare homosexual men, intravenous drug users, and heterosexuals in EuroSIDA, a prospective European cohort of 7331 patients with HIV in terms of starting a HAART treatment regimen, immunologic and virologic response to therapy, and survival. Methods: 6645 patients were included in this analysis. Logistic regression and Cox proportional hazards models were used to investigate the factors associated with use of HAART regimens and survival following recruitment to the EuroSIDA study. Results: In a multivariate logistic regression model, intravenous drug users were significantly less likely to be receiving HAART at recruitment to EuroSIDA (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.37-0.62; p < .0001) when compared with homosexual men. Similarly, during follow-up, intravenous drug users were at a 27% reduced risk of starting HAART, after adjustment for other factors related to starting HAART (relative hazard [RH], 0.73; 95% CI, 0.64-0.82; p < .0001). There were no differences between heterosexual and homosexual patients, and similar results were found within regions of Europe (South, Central and Northern). Among those patients who started HAART, there were no significant differences between exposure groups in CD4 lymphocyte count response to HAART or virologic response to HAART. After adjustment for factors related to survival, intravenous drug users were at a small, but nonsignificant increased risk of death compared with homosexuals (RH 1.16; 95% CI, 0.99-1.38; p = .074). Conclusions: Intravenous drug users were significantly less likely to start HAART, but among those who did, response to therapy was similar to that of other exposure groups. There were no differences in risk of death. If intravenous drug users continue to use HAART less commonly than other exposure groups, it may result in a poorer prognosis, a different spectrum of AIDS-defining illnesses, and differential long-term clinical needs.

Uniform risk of clinical progression despite differences in utilization of highly active antiretroviral therapy: Swiss HIV Cohort Study.

To compare the initiation of highly active antiretroviral therapy (HAART) in HIV-infected patients according to sex, route of HIV acquisition and education, and to assess the impact of differences in utilization on the probability of progression to AIDS. Swiss HIV Cohort Study, a national prospective multi-centre study. A total of 3342 patients, including 1007 (30%) women. HIV was acquired through injection drug use in 1155 (35%) cases and through sex between men in 1172 (35%). Twenty-eight per cent (957) of participants had attained only the minimum level of schooling. At baseline, the median CD4 cell count was 269x10(6)/l cells, median HIV-1 RNA was 4.3 log10 copies/ml and 2917 (87%) were free of AIDS. Kaplan-Meier life tables and Cox proportional hazards regression. During 7007 person-years of follow-up 2285 (69%) patients started HAART and 318 (10%) developed a new AIDS event. In multivariable analysis controlling for CD4 cell count, viral load and disease stage at baseline, the probability of starting HAART was lower in injection drug users compared with men who have sex with men, hazard ratio 0.63 (95% confidence intervals 0.56-0.70) and in patients with minimum schooling compared with those with vocational training, hazard ratio 0.82 (0.75-0.91). The risk of progression to AIDS was similar among men and women, patients with a history of injecting drug use, and patients with lower educational attainment in both univariable and multivariable analysis. HIV-infected injecting drug users and those with lower levels of educational attainment start HAART later than other patient groups. The deferred initiation of therapy in these patients does not, however, appear to translate into an increased risk of clinical disease progression. This observation has important implications for treatment policy and the design of future clinical trials.