CD4 Cell Count Decline Research Articles

Safety of hormonal and intrauterine methods of contraception for women with HIV/AIDS: a systematic review

To determine from the literature whether HIV-infected women who use hormonal or intrauterine contraception are at increased risk of HIV disease progression, other adverse health outcomes, or HIV transmission to uninfected sexual partners. A systematic review. We searched PubMed for articles published in peer-reviewed journals through August 2009 for evidence relevant to all hormonal and intrauterine contraceptive methods and HIV/AIDS. Eight observational studies reported no increased risk of HIV disease progression with hormonal or intrauterine contraceptive use, whereas one randomized controlled trial found increased risks of declining CD4 cell count and death for hormonal contraceptive users compared with intrauterine device users. Women with HIV who used hormonal contraception had increased risks of acquiring sexually transmitted infections compared with women not using hormonal contraception, similar to the risks reported among uninfected women. One study found no association between hormonal or intrauterine contraceptive use and increased risk of HIV transmission to uninfected partners, whereas findings from nine studies examining contraceptive use and viral shedding from the genital tract were inconsistent. Evidence regarding the safety of hormonal and intrauterine contraceptive use among women with HIV remains limited, but generally reassuring regarding adverse health effects, disease transmission to uninfected partners, and disease progression; however, one randomized trial raised concerns about enhanced disease progression among women using hormonal contraception. Preventing unintended pregnancy among women with HIV remains a high priority in public health, both for the health of the woman as well as for the prevention of mother-to-child transmission of HIV.

Accuracy of WHO CD4 cell count criteria for virological failure of antiretroviral therapy

To examine the accuracy of the World Health Organization immunological criteria for virological failure of antiretroviral treatment. Analysis of 10 treatment programmes in Africa and South America that monitor both CD4 cell counts and HIV-1 viral load. Adult patients with at least two CD4 counts and viral load measurements between month 6 and 18 after starting a non-nucleoside reverse transcriptase inhibitor-based regimen were included. WHO immunological criteria include CD4 counts persistently <100 cells/microl, a fall below the baseline CD4 count, or a fall of >50% from the peak value. Virological failure was defined as two measurements > or =10 0000 copies/ml (higher threshold) or > or =500 copies/ml (lower threshold). Measures of accuracy with exact binomial 95% confidence intervals (CI) were calculated. A total of 2009 patients were included. During 1856 person-years of follow up 63 patients met the immunological criteria and 35 patients (higher threshold) and 95 patients (lower threshold) met the virological criteria. Sensitivity [95% confidence interval (CI)] was 17.1% (6.6-33.6%) for the higher and 12.6% (6.7-21.0%) for the lower threshold. Corresponding results for specificity were 97.1% (96.3-97.8%) and 97.3% (96.5-98.0%), for positive predictive value 9.5% (3.6-19.6%) and 19.0% (10.2-30.9%) and for negative predictive value 98.5% (97.9-99.0%) and 95.7% (94.7-96.6%). The positive predictive value of the WHO immunological criteria for virological failure of antiretroviral treatment in resource-limited settings is poor, but the negative predictive value is high. Immunological criteria are more appropriate for ruling out than for ruling in virological failure in resource-limited settings.

African descent is associated with slower CD4 cell count decline in treatment-naive patients of the Swiss HIV Cohort Study

We investigated the effect of descent (African versus European) on the progression of untreated HIV infections in a prospective cohort study of HIV-1-infected individuals. We estimated the linear rate of decline of the CD4 cell count and the setpoint viral load in patients with sufficient data points. The effect of descent was assessed by microltivariate regression models including descent, sex, viral subtype, the earliest date of confirmed infection, age, and the baseline CD4 cell count; the rate of CD4 cell count decline was also analyzed with mixed-effect models and with matched comparisons between patients of African and European descent based on the baseline CD4 cell count. We found that the decline slope of the CD4 cell count was significantly less steep (+26.6 cells/microl per year; 95% confidence interval, 12.3-41.0; P < 0.001) in patients of African descent (n = 123) compared with patients of European descent (n = 463), and this effect was independent of differences in the infecting viral subtypes. Matched comparisons confirmed the effect of African descent (P < 0.001). Remarkably, the rate of CD4 cell count decline depended strongly on the viral setpoint in patients of European descent (-46.3 cells/microl per year/log10 RNA copies/ml; 95% confidence interval, -55.8 to -36.7; P < 0.001) but not in patients of African descent. Slower disease progression in patients of African descent might be related to host factors allowing better tolerance of high virus levels in patients of African descent compared with patients of European descent.

The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy

Over 150,000 Malawians have started antiretroviral therapy (ART), in which first-line therapy is stavudine/lamivudine/nevirapine. We evaluated drug resistance patterns among patients failing first-line ART on the basis of clinical or immunological criteria in Lilongwe and Blantyre, Malawi. Patients meeting the definition of ART failure (new or progressive stage 4 condition, CD4 cell count decline more than 30%, CD4 cell count less than that before treatment) from January 2006 to July 2007 were evaluated. Among those with HIV RNA of more than 1000 copies/ml, genotyping was performed. For complex genotype patterns, phenotyping was performed. Ninety-six confirmed ART failure patients were identified. Median (interquartile range) CD4 cell count, log10 HIV-1 RNA, and duration on ART were 68 cells/microl (23-174), 4.72 copies/ml (4.26-5.16), and 36.5 months (26.6-49.8), respectively. Ninety-three percent of samples had nonnucleoside reverse transcriptase inhibitor mutations, and 81% had the M184V mutation. The most frequent pattern included M184V and nonnucleoside reverse transcriptase inhibitor mutations along with at least one thymidine analog mutation (56%). Twenty-three percent of patients acquired the K70E or K65R mutations associated with tenofovir resistance; 17% of the patients had pan-nucleoside resistance that corresponded to K65R or K70E and additional resistance mutations, most commonly the 151 complex. Emergence of the K65R and K70E mutations was associated with CD4 cell count of less than 100 cells/microl (odds ratio 6.1) and inversely with the use of zidovudine (odds ratio 0.18). Phenotypic susceptibility data indicated that the nucleoside reverse transcriptase inhibitor backbone with the highest activity for subsequent therapy was zidovudine/lamivudine/tenofovir, followed by lamivudine/tenofovir, and then abacavir/didanosine. When clinical and CD4 cell count criteria are used to monitor first-line ART failure, extensive nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance emerges, with most patients having resistance profiles that markedly compromise the activity of second-line ART.

Estimating the public health impact of the effect of herpes simplex virus suppressive therapy on plasma HIV-1 viral load

Trials of herpes simplex virus (HSV) suppressive therapy among HSV-2/HIV-1-infected individuals have reported an impact on plasma HIV-1 viral loads (PVLs). Our aim was to estimate the population-level impact of suppressive therapy on female-to-male HIV-1 sexual transmission. By comparing prerandomization and postrandomization individual-level PVL data from the first two HSV suppressive therapy randomized controlled trials in sub-Saharan Africa, we estimated the effect of treatment on duration of asymptomatic infection and number of HIV-1 transmission events for each trial. Assuming that a reduction in PVL is accompanied by an increased duration of HIV-1 asymptomatic infection, 4-6 years of HSV suppressive therapy produce a 1-year increase in the duration of this stage. To avert one HIV-1 transmission requires 8.8 [95% confidence interval (CI), 5.9-14.9] and 11.4 (95% CI, 7.8-27.5) women to be treated from halfway through their HIV-1 asymptomatic period, using results from Burkina Faso and South African trials, respectively. Regardless of the timing of treatment initiation, 51.6 (95% CI, 30.4-137.0) and 66.5 (95% CI, 36.7-222.6) treatment-years are required to avert one HIV-1 infection. Distributions of set-point PVL values from sub-Saharan African populations suggest that unintended adverse consequences of therapy at the population level (i.e. increased HIV-1 transmission due to increased duration of infection) are unlikely to occur in these settings. HSV suppressive therapy may avert relatively few HIV-1 transmission events per person-year of treatment. Its use as a prevention intervention may be limited; however, further research into its effect on rate of CD4 cell count decline and the impact of higher dosing schedules is warranted.

Rapid CD4+ Cell Decrease After Transient cART Initiated During Primary HIV Infection (ANRS PRIMO and SEROCO Cohorts)

To modelize the rate of CD4 cell count decline and its determinants after cessation of combination antiretroviral therapy (cART) started during primary HIV infection (PHI) and compare it with never-treated patients. Kinetics of CD4 counts were analyzed on the square root scale by using a mixed-effects model in 170 patients who received cART during PHI from the Primary Infection (PRIMO) cohort and 123 never-treated patients from the Seroconverters (SEROCO) cohort. After cART interruption in the PRIMO cohort, the CD4 cell count fell rapidly during the first 5 months and more slowly thereafter. The timing of treatment initiation had no influence on the rate of CD4 cell decline. In contrast, a larger increase in CD4 cell counts during cART was associated with a steeper decline and a larger loss of CD4 cells after treatment interruption. The mean CD4 cell loss 3 years postinterruption was 383 cells per microliter. In the SEROCO cohort, the CD4 T-cell decline was less steep (3-year CD4 loss 239 cells/microL). As a result, the mean CD4 cell counts were similar (416 cells/microL) 3 years after cART interruption (PRIMO) or after infection (SEROCO). These data question the benefit of a limited course of cART even when initiated within 3 months after PHI diagnosis.

HIV-1 viral rebound dynamics after a single treatment interruption depends on time of initiation of highly active antiretroviral therapy

An important pending question is whether temporary highly active antiretroviral therapy during primary HIV infection can influence viral rebound dynamics and the subsequently established viral setpoint, through preservation and enhancement of HIV-1-specific immune responses, or through other mechanisms. We included all patients from two prospective studies who underwent a single treatment interruption while being well suppressed on highly active antiretroviral therapy. One group started highly active antiretroviral therapy during primary HIV infection, and the other group started it during chronic HIV infection with CD4 cell counts above 350 cells/microl. Data were collected up to 48 weeks from treatment interruption. The median time to viral rebound was analysed for three levels of viraemia: 50, 500 and 5000 copies HIV-RNA/ml plasma. The median time to viral rebound was significantly longer in primary HIV infection patients (n = 24) than in chronic HIV infection patients (n = 46): 8 versus 4 weeks (P < 0.001 for all three endpoints). In two primary HIV infection patients, no rebound of plasma HIV-1 RNA over 50 copies/ml occurred. In the first 4 weeks after treatment interruption, CD4+ T-cell counts declined with a median of -5.0 cells/microl blood per week in the primary HIV infection group and -45 cells/microl blood per week in the chronic HIV infection group (P < 0.05). From week 4 to 48, the decline in CD4+ T-cell count was similar in both groups. Plasma viral load and CD4 dynamics after a single interruption of highly active antiretroviral therapy were different for primary HIV infection and chronic HIV infection patients. Viral rebound is delayed or absent and early CD4 cell count decline after treatment interruption is less pronounced in primary HIV infection patients.

British HIV Association guidelines for HIV‐associated malignancies 2008

British HIV Association guidelines for HIV‐associated malignancies 2008

Anemia and Decline of CD4 Cell Count in HIV+ Drug Users in Miami

Objective:This study investigates the association of anemia with HIV disease progression and survival over 30 months in HIV+ drug users in Miami.Methods:After obtaining consent, demographic and medical questionnaires were completed every 6 months for 30 months in HIV+ drug users. Blood was drawn for CD4 cell count, viral load, and CBC. Anemia was defined as hemoglobin &lt;12g/dL in women and &lt;14g/dL in men, and hematocrit&lt;37% in women and &lt;42% in men. Kaplan Meier Estimation was used to evaluate the rate of decline of CD4 cell count and mortality over 30 months.Results:Of 231 participants, 77% were black, and 73% were men. Mean age was 42 years ± 7.1. The prevalence of anemia was 46% (n=106). Of those with anemia, only 19% had macrocytic/normochromic anemia and 0.05% microcytic/hypochromic anemia, suggesting nutritional deficiency. Anemia was significantly associated with a more rapid decline of CD4 cell count to below 200 cells/μL (p&lt;0.001) when compared to participants without anemia. There was also a trend in decreased survival overtime in those who had anemia compared to those without anemia, (80% vs. 94%, p=0.094).Conclusions:Nutritional etiologies of anemia do not seem to be the predominant cause of anemia in this cohort. Anemia in our cohort was strongly related to advanced HIV disease and efforts to identify the cause and provide treatment may help to delay disease progression.Funded by NIDA

CCR5 or CXCR4 use influences the relationship between CD4 cell depletion, NKp44L expression and NK cytotoxicity in SHIV-infected macaques

HIV-1 infection is characterized by a progressive decline of CD4 cell count, the underlying mechanisms of which are still debated. We recently found that during HIV-1 infection, CD4 T cells overexpress a ligand of the NK activating receptor NKp44 (NKp44L) and are sensitized to NK cytolytic activity. The expression of NKp44L is triggered by a highly conserved motif of gp41 (3S) and is inhibited by anti-3S antibodies. To assess whether viral tropism can affect NKp44L expression, NK cytotoxicity, and anti-3S antibodies production, 10 macaques were infected either with the CCR5 tropic SHIV162P3 or with a CXCR4/CCR5 dual-tropic SHIV89.6P. In SHIV162P3-infected macaques, expression of NKp44L was inversely correlated with anti-3S antibodies, in relation to CD4 depletion and NK cytotoxicity. By contrast, no such correlation was found in macaques infected with SHIV89.6P which, induced a rapid decline of CD4 T cells. These results highlight the key role played by NK cells in CD4 cell count decline with respect to coreceptor usage, and provided the setting to investigate new strategies for preventive and/or therapeutic immunization to stimulate anti-3S antibodies.

HIV infection in ageing population Case report of three patients over 75 years old

Epidemiological data shows, that among HIV infected patients population of persons older then 50 years is steadily growing. This group consists of patients treated successfully with ART and growing older on treatment, and of patients diagnosed with HIV in older age. Data shows, that older age is connected with faster progression to AIDS, faster decline in CD4 cell count and that response to ART is poorer in this group when compare with younger population. Age is a risk factor of developing cardiovascular disease, liver, kidneys and bone disorders. It become apparent, that medical standard of care for older HIV patients needs adjustment. This paper describes three cases of patients age 75 years or more, the oldest patients under care in the clinic in the year 2008.

Prevalence of Cryptosporidium, Cyclospora cayetanensis and Isospora belli infection among diarrheal patients in South India

The emerging protozoan parasites Cryptosporidium, Cyclospora cayetanensis and Isospora belli have altered the etiological spectrum of diarrhea. The progressive decline in CD4 cell count in AIDS patients and lack of active immunity in the face of exposure to contaminated food and water in young children make these groups of persons particularly susceptible to protracted and severe diarrhea caused by the above parasites. Cryptosporidiosis is caused by human as well as several zoonotic species. The present study was undertaken to examine the prevalence of Cryptosporidium species, C. cayetanensis and I .belli among these two susceptible populations in comparison with adult immunocompetent individuals with diarrhea and to identify the Cryptosporidium species prevalent in these populations. A total of 447 children under the age of 5 years, 175 HIV-seropositive adults and 200 HIV seronegative adults with diarrhea attending tertiary care hospitals located in the twin cities of Secunderabad and Hyderabad in South India were included in the study. Single fecal samples were collected. Wet mounts and modified Ziehl Neelsen stained smears made from concentrated fecal specimens were screened microscopically for oocysts of Cryptosporidium, Cyclospora cayetanensis and Isospora belli. DNA extracted from fecal samples positive for Cryptosporidium was subjected to PCR RFLP for species identification. Cryptosporidium was detected in all the three groups, I.e. children (8.7%), HIV-seropositive adults (6.85%), and HIV-seronegative adults (1%). Isospora and Cyclospora were detected only among HIV- seropositive persons at a frequency of 16% and 1% respectively. C. hominis (71.7%) and C. parvum (18.9%) were the only 2 species of Cryptosporidium detected.

Effects of Cotrimoxazole on Hematologic Parameters in HIV-Infected Adults in a Community-Based Clinic in Entebbe, Uganda

We and others have previously reported reduced mortality and malaria incidence with cotrimoxazole prophylaxis for HIV-1-infected adults in Uganda and elsewhere. This evidence has led to widespread implementation of cotrimoxazole prophylaxis for HIV-1-infected persons in sub-Saharan Africa. The World Health Organization (WHO) recommends that implementation at the country level should be carefully monitored and that this monitoring should evaluate rates of toxicity including hematologic toxicity through the measurement of blood cell counts every 6 months. Cotrimoxazole interferes with folate metabolism and there have been several reports of hematologic abnormalities associated with its use. These abnormalities could potentially worsen if cotrimoxazole is used in conjunction with myelosuppressive or antifolate drugs such as zidovudine. There is scanty evidence of these abnormalities associated with cotrimoxazole use in Uganda however. Cotrimoxazole prophylaxis was introduced in August 2000 in an open cohort of HIV-1-infected participants in EntebbeUganda. Here we report hematologic changes in participants before and after the introduction of cotrimoxazole. (excerpt)

AIDS-Related Cancer and Severity of Immunosuppression in Persons With AIDS

The incidence of Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer has been declining among persons with AIDS. We investigated the association between cancer risk and CD4 cell count among such persons. Data from US AIDS registries were linked to local cancer registry data. Cancer incidence per 100,000 person-years was determined for the 4-27 months from the onset of AIDS from January 1, 1990, through December 31, 1995--before highly active antiretroviral therapy (HAART) became available--and from January 1, 1996, through December 31, 2002. The relationships between CD4 count at AIDS onset and cancer incidence were assessed by proportional hazards models. Among 325,516 adults with AIDS, the incidence of Kaposi sarcoma was lower in 1996-2002 (334.6 cases per 100,000 person-years) than in 1990-1995 (1838.9 cases per 100,000 person-years), and the incidence of non-Hodgkin lymphoma followed a similar pattern (i.e., 390.1 cases per 100,000 person-years in 1996-2002 and 1066.2 cases per 100,000 person-years in 1990-1995). In 1996-2002, for each decline in CD4 cell count of 50 cells per microliter of blood, increased risks were found for Kaposi sarcoma (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.33 to 1.50), for central nervous system non-Hodgkin lymphoma subtypes (HR = 1.85, 95% CI = 1.58 to 2.16), and for non-central nervous system diffuse large B-cell lymphoma (HR = 1.12, 95% CI = 1.04 to 1.20) but not for non-central nervous system Burkitt lymphoma (HR = 0.93, 95% CI = 0.81 to 1.06). Cervical cancer incidence was higher in 1996-2002 (86.5 per 100,000 person-years) than in 1990-1995 (64.2 per 100,000 person-years), although not statistically significantly so (relative risk [RR] = 1.41, 95% CI = 0.81 to 2.46). After adjustment for age, race, and sex or mode of HIV exposure, the risks for Kaposi sarcoma (RR = 0.22, 95% CI = 0.20 to 0.24) and for non-Hodgkin lymphoma (RR = 0.40, 95% CI = 0.36 to 0.44) were lower in the period of 1996-2002 than in 1990-1995. Similar relationships of these cancers to CD4 count were observed for 1990-1995. Both before and after HAART was available, CD4 count was strongly associated with risks for Kaposi sarcoma and non-Hodgkin lymphoma but not for cervical cancer and Burkitt lymphoma. The decreasing incidences of most AIDS-associated cancers in persons with AIDS during the 1990s are consistent with improving CD4 counts after HAART introduction in 1996.

HIV‐1 Subtype D Infection Is Associated with Faster Disease Progression than Subtype A in Spite of Similar Plasma HIV‐1 Loads

We investigated the effect of human immunodeficiency virus type 1 (HIV-1) subtype on disease progression among 145 Kenyan women followed from the time of HIV-1 acquisition. Compared with those infected with subtype A, women infected with subtype D had higher mortality (hazard ratio, 2.3 [95% confidence interval, 1.0-5.6]) and a faster rate of CD4 cell count decline (P=.003). The mortality risk persisted after adjustment for plasma HIV-1 load. There were no differences in plasma viral load by HIV-1 subtype during follow-up. HIV-1 subtype D infection is associated with a >2-fold higher risk of death than subtype A infection, in spite of similar plasma HIV-1 loads.

Intermittent therapy for the treatment of chronic HIV infection

Intermittent therapy for the treatment of chronic HIV infection

Treatment interruption in advanced failing patients

To discuss the rationale and results of clinical trials examining treatment interruption in HIV-positive patients with advanced disease who are experiencing therapy failure. In the past it was thought that treatment interruptions in patients experiencing therapy failure might bring about an improved virologic response to treatment via drug re-sensitization. All of the major international clinical trials, with the exception of the Giga-HAART trial, however, have found no benefit of treatment interruption in this group of patients. Moreover, most of the trials have shown an increased risk for disease progression or death. It has also been shown that even patients with no or few treatment options, staying on a failing regimen may have some clinical benefit relative to treatment interruption. Treatment interruption in advanced failing patients may be a dangerous course of action due to the increased risk of clinical disease progression and decline in CD4 cell count. Staying on therapy, even a failing therapy, may have some benefit, at least until new drugs become available.

HIV‐1 Disease Progression in Breast‐Feeding and Formula‐Feeding Mothers: A Prospective 2‐Year Comparison of T Cell Subsets, HIV‐1 RNA Levels, and Mortality

There is conflicting evidence regarding the effects of breast-feeding on maternal mortality from human immunodeficiency virus type 1 (HIV-1) infection, and little is known about the effects of breast-feeding on markers of HIV-1 disease progression. HIV-1-seropositive women were enrolled during pregnancy and received short-course zidovudine. HIV-1 RNA levels and CD4 cell counts were determined at baseline and at months 1, 3, 6, 12, 18, and 24 postpartum and were compared between breast-feeding and formula-feeding mothers. Of 296 women, 98 formula fed and 198 breast-fed. At baseline, formula-feeding women had a higher education level and prevalence of HIV-1-related illness than did breast-feeding women; however, the groups did not differ with respect to CD4 cell counts and HIV-1 RNA levels. Between months 1 and 24 postpartum, CD4 cell counts decreased 3.9 cells/ microL/month (P<.001), HIV-1 RNA levels increased 0.005 log(10) copies/mL/month (P=.03), and body mass index (BMI) decreased 0.03 kg/m(2)/month (P<.001). The rate of CD4 cell count decline was higher in breast-feeding mothers (7.2 cells/ microL/month) than in mothers who never breast-fed (4.0 cells/ microL/month) (P=.01). BMI decreased more rapidly in breast-feeding women (P=.04), whereas HIV-1 RNA levels and mortality did not differ significantly between breast-feeding and formula-feeding women. Breast-feeding was associated with significant decreases in CD4 cell counts and BMI. HIV-1 RNA levels and mortality were not increased, suggesting a limited adverse impact of breast-feeding in mothers receiving extended care for HIV-1 infection.

A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised trial

Long-term data from randomised trials on the consequences of treatment with a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or both are lacking. Here, we report results from the FIRST trial, which compared initial treatment strategies for clinical, immunological, and virological outcomes. Between 1999 and 2002, 1397 antiretroviral-treatment-naive patients, presenting at 18 clinical trial units with 80 research sites in the USA, were randomly assigned in a ratio of 1:1:1 to a protease inhibitor (PI) strategy (PI plus nucleoside reverse transcriptase inhibitor [NRTI]; n=470), a non-nucleoside reverse transcriptase inhibitor (NNRTI) strategy (NNRTI plus NRTI; n=463), or a three-class strategy (PI plus NNRTI plus NRTI; n=464). Primary endpoints were a composite of an AIDS-defining event, death, or CD4 cell count decline to less than 200 cells per mm3 for the PI versus NNRTI comparison, and average change in CD4 cell count at or after 32 months for the three-class versus combined two-class comparison. Analyses were by intention-to-treat. This study is registered ClinicalTrials.gov, number NCT00000922. 1397 patients were assessed for the composite endpoint. A total of 388 participants developed the composite endpoint, 302 developed AIDS or died, and 188 died. NNRTI versus PI hazard ratios (HRs) for the composite endpoint, for AIDS or death, for death, and for virological failure were 1.02 (95% CI 0.79-1.31), 1.07 (0.80-1.41), 0.95 (0.66-1.37), and 0.66 (0.56-0.78), respectively. 1196 patients were assessed for the three-class versus combined two-class primary endpoint. Mean change in CD4 cell count at or after 32 months was +234 cells per mm3 and +227 cells per mm3 for the three-class and the combined two-class strategies (p=0.62), respectively. HRs (three-class vs combined two-class) for AIDS or death and virological failure were 1.15 (0.91-1.45) and 0.87 (0.75-1.00), respectively. HRs (three-class vs combined two-class) for AIDS or death were similar for participants with baseline CD4 cell counts of 200 cells per mm3 or less and of more than 200 cells per mm3 (p=0.38 for interaction), and for participants with baseline HIV RNA concentrations less than 100 000 copies per mL and 100,000 copies per mL or more (p=0.26 for interaction). Participants assigned the three-class strategy were significantly more likely to discontinue treatment because of toxic effects than were those assigned to the two-class strategies (HR 1.58; p<0.0001). Initial treatment with either an NNRTI-based regimen or a PI-based regimen, but not both together, is a good strategy for long-term antiretroviral management in treatment-naive patients with HIV.

Structured treatment interruptions (STI) in chronic unsuppressed HIV infection in adults

Structured treatment interruptions (STI) in chronic unsuppressed HIV infection in adults