Excessive early mortality in the first year of treatment in HIV type 1-infected patients initiating antiretroviral therapy in resource-limited settings

The response to treatment and risk factors for early mortality following initiation of combination antiretrovirals(ARVs) in a cohort of African patients are described in a retrospective cohort design. Medical history, laboratory parameters, and mortality data were reviewed for patients initiating ARVs in 12 clinical centers in Mozambique, Tanzania, and Malawi. Among 3456 HIV-1-infected patients who received ARVs for more than 6 months, at baseline 72% had WHO clinical stages 3/4, 7% had a viral load 400 copies/ml, and 38% had a CD4 cell count >200/microl. One year later, 78% had undetectable virus loads and 79% had CD4 cell counts >200 cells/mm3. In the first year of HAART 260 deaths occurred (97 per 1000 person/years) with mortality peaking in the first 3 months. The highest mortality was observed in patients with low BMI, low hemoglobin levels, and CD4 values <200 cells/microl at baseline. Mortality rates following initiation of HAART are higher in patients in resource-limited areas, particularly in the first 90 days following treatment initiation.HAART initiated at higher CD4 cell count levels, especially among malnourished and/or anemic patients, will carry significant public health impact.     

Impact of genotypic drug resistance mutations on clinical and immunological outcomes in HIV-infected adults on HAART in West Africa

OBJECTIVES: To analyse the association between the presence of resistance mutations and treatment outcomes. The impact of HIV-1 drug resistance mutations in African adults on HAART has so far never been reported. METHODS: In 2004 in Abidjan, C?te d'Ivoire, 106 adults on HAART had plasma viral load measurements. Patients with detectable viral loads had resistance genotypic tests. Patients were followed until 2006. Main outcomes were serious morbidity and immunological failure (CD4 cell count < 200 cells/microl). RESULTS: At study entry, the median previous time on HAART was 37 months and the median CD4 cell count was 266 cells/microl; 58% of patients had undetectable viral loads, 20% had detectable viral loads with no major resistance mutations, and 22% had detectable viral loads with one or more major mutations. The median change in CD4 cell count between study entry and study termination was +129 cells/microl in patients with undetectable viral loads, +51 cells/microl in those with detectable viral loads with no mutations and +3 cells/microl in those with detectable viral loads with resistance mutations. Compared with patients with undetectable viral loads, those with detectable viral loads with resistance mutations had adjusted hazard ratios of immunological failure of 4.32 (95%CI 1.38-13.57, P = 0.01). One patient died. The 18-month probability of remaining free of morbidity was 0.79 in patients with undetectable viral loads and 0.69 in those with resistance mutations (P = 0.19). CONCLUSION: In this setting with restricted access to second-line HAART, patients with major resistance mutations had higher rates of immunological failure, but most maintained stable CD4 cell counts and stayed alive for at least 20 months.     

Impact of baseline viral load and adherence on survival of HIV-infected adults with baseline CD4 cell counts > or = 200 cells/microl

BACKGROUND: Baseline plasma HIV RNA levels > 100 000 copies/ml have been associated with elevated mortality rates after the initiation of HAART. There is uncertainty regarding the optimal strategy for patients with high plasma HIV RNA but CD4 cell count > or = 200 cells/microl. OBJECTIVE: To evaluate the impact of baseline plasma HIV RNA on survival among patients with CD4 cell counts > or = 200 cells/microl. METHODS: Patients were stratified by plasma HIV RNA, CD4 cell count and adherence level. Mortality rates were evaluated using Kaplan-Meier methods and Cox regression. RESULTS: Among 1166 patients initiating HAART with a CD4 cell count > or = 200 cells/microl, a baseline HIV RNA > or = 100 000 copies/ml was statistically associated with elevated mortality among non-adherent patients (log-rank P = 0.032), but not for adherent patients (log-rank P = 0.690). In a multivariate Cox model comparing patients with a baseline CD4 cell count > or = 200 cells/microl and a baseline plasma HIV RNA < 100 000 copies/ml, the mortality rate was statistically similar among patients with a baseline CD4 cell count > or = 200 cells/microl and a baseline plasma HIV RNA > or = 100 000 copies/ml (relative hazard, 1.21; 95% confidence interval, 0.89-1.65; P = 0.232). CONCLUSION: HIV RNA > or = 100 000 copies/ml was only associated with mortality among HIV-infected patients initiating HAART with CD4 cell counts > or= 200 cells/microl if the patients were non-adherent.     

Polymorphisms of Cx(3)CR1 and CXCR6 receptors in relation to HAART therapy of HIV type 1 patients

The chemokine polymorphisms CXCR6-3E/K, In1.1T/C, H7 haplotype, CX(3)CR1-V249I, and CX(3)CR1-T280M have been shown to affect the course of HIV infection. We studied their influence on immunologic and virologic response to HAART in a group of 143 HIV-1 patients. We performed Kaplan-Meier analysis using the following end-point criteria: (1) time from HAART initiation to undetectable viral load (VL < 50 copies/ml), (2) maximum duration of viral suppression, (3) time from HAART administration until CD4 elevation above 200 cells/microl for patients with baseline CD4 below 200 cells/microl and above 500 cells/microl for patients with baseline CD4 between 200 and 500 cells/microl, respectively, and (4) time from HAART initiation until CD4 reduction below baseline values. Our results revealed an improved immunologic response to HAART in patients with the CX(3)CR1-249I or CX(3)CR1-280M allele. On the contrary, patients with initial VL suppression due to HAART showed a faster virologic failure in the presence of the CXCR6-3K allele. The In1.1T/C polymorphism and H7 haplotype did not reveal any specific effect on HAART response.     

Improved outcomes with earlier initiation of highly active antiretroviral therapy among human immunodeficiency virus-infected patients who achieve durable virologic suppression: longer follow-up of an observational cohort study

On the basis of studies with relatively short follow-up, treatment guidelines currently recommend that highly active antiretroviral therapy (HAART) be initiated in asymptomatic human immunodeficiency virus-infected patients when the CD4+ lymphocyte count is < or =200 cells/mm3. We assessed the development of a new opportunistic infection or death among 1173 patients initiating HAART. Durable virologic suppression was defined as having more undetectable (<400 copies/mL) than detectable virus loads after the initiation of therapy. The median durations of therapy and follow-up were 29 and 36 months, respectively. Among patients who achieved durable virologic suppression, those with baseline CD4+ lymphocyte counts of <200 cells/mm3 tended to progress faster than those with baseline CD4+ lymphocyte counts of 201-350 cells/mm3 (P=.09) and progressed faster than those with baseline CD4+ lymphocyte counts of >350 cells/mm3 (P=.01). Among those with durable virologic suppression, there was no difference in disease progression between those with baseline CD4+ lymphocyte counts of 201-350 cells/mm3 and those with durable virologic suppression with baseline CD4+ lymphocyte counts of >350 cells/mm3 (P=.40). Initiating HAART with a CD4+ lymphocyte count of <200 cells/mm3 was associated with a higher risk of disease progression, even with durable virologic suppression. HAART should be initiated at CD4+ lymphocyte counts of >200 cells/mm3.     

Disease progression in patients with virological suppression in response to HAART is associated with the degree of immunological response

OBJECTIVE: To determine if immunological response is associated with disease progression in patients with virological suppression after initiating HAART. DESIGN: A cohort study of 1084 treatment-naive participants in the British Columbia HIV/AIDS Drug Treatment Program who had achieved viral loads < 500 copies/ml at 3-9 months after initiating triple-drug therapy. METHODS: Cox proportional hazards was used to model the association with disease progression of baseline variables, change in CD4 cell counts and CD4 cell count strata at 6 months. Logistic regression analysis was used to examine associations with two definitions of poor immunological response. RESULTS: Patients were followed for a median of 51.4 months. In univariate analyses, increases in CD4 cell counts of < 25 cells/microl and absolute CD4 cell counts of < 200 cells/microl were associated with an increased risk of death or new AIDS events. Two mulitivariate models, one including baseline CD4 cell count and change in CD4 cell count from baseline and the other including only absolute CD4 cell counts at 6 months, were found to predict disease progression in this setting. Increases in CD4 cell count of < 25 cells/microl were associated with increasing age and inversely associated with low baseline CD4 cell counts, high baseline viral loads and good adherence to therapy. CD4 cell counts of < 200 cells/microl at 6 months were associated with low baseline CD4 cell counts and having AIDS at baseline. CONCLUSION: Patients with virological suppression are still at risk for HIV disease progression if adequate immunological responses are not achieved.     

Immunological and virological responses to highly active antiretroviral therapy in a non-clinical trial setting in a developing Caribbean country

OBJECTIVE: Few data exist on the efficacy of antiretroviral therapy in individuals infected with HIV in the Caribbean. We evaluated the virological and immunological responses of HIV-infected adults starting highly active antiretroviral therapy (HAART). DESIGN: This was a prospective observational cohort study. METHODS: A total of 158 antiretroviral-naive patients who initiated HAART between January 2002 and March 2003, and completed at least 6 months of treatment and follow up, were included in the analysis. The response to therapy was assessed by changes in CD4 cell counts and viral loads from baseline. The mean increase in CD4 cell count, the rate of virological success (a viral load of <50 HIV-1 RNA copies/mL) and the rate of immunological success (an increase in CD4 cell count of > or =50 cells/microL over the baseline value) after commencing HAART were measured. RESULTS: In total, 82% of patients (123 of 150) achieved viral loads of <50 copies/mL after 6 months of therapy. Viral success rate after 6 months of HAART was similar irrespective of gender, pre-HAART CD4 cell count and pre-HAART viral load. However, patients older than 40 years were significantly more likely to achieve virological success than those younger than 40 years. At 6 months after starting HAART, 79.5% of patients were estimated to have achieved immunological success and 17.9% had an increase in CD4 cell count of > or =200 cells/microL over the baseline value. The median increase in CD4 cell count for the 156 patients who had CD4 cell counts at baseline and at 6 months of therapy was 122 cells/microL. CONCLUSION: In this cohort of antiretroviral-naive HIV-infected adults, there was a high rate of virological and immunological success after 6 months of HAART, irrespective of the pre-HAART viral load and CD4 cell count.     

Immunologic and virologic responses to HAART in severely immunocompromised HIV-1-infected children

OBJECTIVE: To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS. DESIGN: A prospective observational study. SETTING: Two pediatric HIV clinics. PARTICIPANTS: Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4 < or =6%). INTERVENTION: HAART (one protease inhibitor and one or more nucleoside analogs). Diphtheria and tetanus immunization in six patients after 18 months of therapy. MAIN OUTCOME MEASURES: Changes in percentage of CD4 cells and plasma HIV-1 RNA levels; post-treatment assays of lymphoproliferative responses to recall antigens; CD4 cell memory phenotype. RESULTS: Median duration of follow-up was 18.8 months (range, 7.5-28 months). At baseline the CD4 cell percentage was 2% (range, 0-6%), this increased significantly to 16% (range, 3-48%) above baseline at 12 months (P = 0.002). The mean maximum CD4 cell increase was 20.7% (range 4-48%) which corresponds to 657x10(6) cells/l (range, 30-2240x10(6) cells/l) above baseline. By contrast, the median viral load was not significantly lower at 12 months than at baseline (P = 0.34), and only 25% of the patients had sustained undetectable viral load. Of the reconstituted CD4 cells 70% were naive, and none of the subjects had lymphoproliferative responses to tetanus and diphtheria although 40% did develop responses to Candida, an environmental antigen. A single immunization with diphtheria and tetanus toxoid produced lymphoproliferative responses to tetanus in three out of six patients. CONCLUSIONS: HAART was associated with sustained increases in CD4 cell counts, despite a high incidence of 'virologic failure'. CD4 counts and the proportion of naive cells were higher than have been reported in adults, which may be a reflection of greater thymic activity in children. Memory cell clones for antigens encountered in the past which are not prevalent before therapy could not be expanded without additional antigenic exposure.     

Impact of 5 years of maximally successful highly active antiretroviral therapy on CD4 cell count and HIV-1 DNA level

OBJECTIVES: To evaluate the impact on CD4 cell count and HIV-1 DNA level in peripheral blood mononuclear cells (PBMC) of long-term highly active antiretroviral therapy (HAART) in the setting of maximal success, i.e., constant plasma HIV-1 RNA load suppression. DESIGN: Retrospective analysis of patients selected for a constantly undetectable plasma HIV-1 RNA load since HAART initiation. METHODS: HIV-1 DNA was measured in PBMC using a real-time polymerase chain reaction assay. Loess estimates and regression analysis were used for modelling the variations of the CD4 cell count and HIV DNA level over time. RESULTS: The study included 41 patients chronically infected with HIV-1 who had been taking HAART for a median duration of 60.4 months and had an undetectable plasma HIV RNA load ever since the first 6 months of HAART; 25 were tested for HIV-1 DNA. The mean CD4 cell count increase was high during the first 18 months on therapy (168 x 10 cells/l per year), much lower afterwards (38 x 10 cells/l per year), independently of the baseline CD4 cell count. Most of the patients (73.2%) reached a CD4 cell count constantly > or = 400 x 10/l during follow-up. HIV-1 DNA showed a mean decrease of 0.48 log10 copies/10 PBMC during the first year, of 0.18 log10 copies/10 PBMC per year during the 2nd and 3rd years, but no significant decrease afterwards. CONCLUSIONS: These results question the benefit of very long-term maintenance of HAART in terms of CD4 gain and HIV-1 DNA reduction.     

Predictive factors for immunological and virological endpoints in Thai patients receiving combination antiretroviral treatment

BACKGROUND: Routine CD4 count and HIV viral load monitoring is a financial barrier in developing countries. METHODS: We assessed factors associated with CD4 counts < or =200 cells/microL and detectable viral load in Thai HIV-infected patients receiving antiretroviral therapy (ART) at the HIV Netherlands Australia Thailand Research Collaboration and the Thai Red Cross AIDS Research Centre (HIV-NAT). Univariate and multivariate Cox proportional hazards models for multiple treatment failures were used to determine factors related to CD4 counts < or =200 cells/microL and detectable viral load. Multivariate Cox proportional hazards models for CD4 counts < or =200 cells/microL were developed with and without viral load in order to build models applicable to contexts in which viral load is not available. RESULTS: Four hundred and seventeen patients were included in the study. Fifty-four per cent were male, and the median CD4 count and log(10) viral load at baseline were 283 cells/microL and 4.3 log(10) HIV-1 RNA copies/mL, respectively. Independent factors related to CD4 count < or =200 cells/microL were CD4 count at baseline [hazards ratio (HR) 0.20/100 cells/microL; 95% confidence interval (CI) 0.17-0.23] and changes in CD4 count (HR 0.22/100 cells/microL; 95% CI 0.17-0.28). Factors in multivariate models (in which viral load was considered for inclusion) were CD4 count at baseline (HR 0.21/100 cells/microL; 95% CI 0.18-0.24), changes in CD4 count (HR 0.25/100 cells/microL; 95% CI 0.19-0.32) and detectable viral load (HR 1.94; 95% CI 1.20-3.13). Predictive factors (independent of viral load) were triple ART or highly active antiretroviral therapy (HAART) (HR 0.28; 95% CI 0.22-0.36) and detectable viral load at baseline (HR 2.96; 95% CI 2.24-3.91). Conclusions CD4 count at baseline and changes in CD4 count were important in predicting CD4 counts < or =200 cells/microL. Triple ART and detectable viral load at baseline were important in predicting detectable viral load.     

CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study

BACKGROUND: Highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-1 infection allows recovery of CD4 T lymphocytes. Few studies have explored the long-term T-lymphocyte responses to HAART. METHODS: Plasma HIV-1 RNA levels and CD4 and CD8 T-lymphocyte counts were longitudinally analyzed over 4 years in 2235 participants of the Swiss HIV Cohort, commencing HAART between 1996 and 1997. The CD4 T-lymphocyte count increase, the percentage of individuals with a CD4 T-lymphocyte count of 500/microL or greater and less than 200/microL, and the determinants of CD4 T-lymphocyte recovery were evaluated in individuals treated with continuous (CONT; n = 985) and discontinuous (DISCONT; n = 1250) HAART. RESULTS: At 4 years, 69.5% of subjects (CONT, 84.5%; DISCONT, 53.6%; P<.001) showed HIV-1 RNA levels below 400 copies/mL, while the median CD4 T-lymphocyte count increased from 190/microL to 423/microL (CONT, 486/microL; DISCONT, 343/microL; P<.001). Of the 2235 participants, 38.8% (CONT, 47.7%; DISCONT, 29.4%; P<.001) reached a CD4 T-lymphocyte count of 500/microL or greater, but in 15.6%, CD4 T-lymphocyte count remained below 200/microL (CONT, 5.9%; DISCONT, 25.9%; P<.001). Larger increases in CD4 T-lymphocyte count were associated with higher baseline HIV-1 RNA, a larger percentage of undetectable HIV-1 RNA levels, lower baseline CD8 T-lymphocyte count, and younger age. Individuals reaching a CD4 T-lymphocyte count of 500/microL or greater at 4 years were characterized by higher nadir and baseline CD4 T-lymphocyte counts and a more sustained reduction of HIV-1 RNA levels. CONCLUSIONS: At 4 years, only 39% of individuals treated with HAART reached a CD4 T-lymphocyte count of 500/microL or greater, and 16% with CD4 T-lymphocyte counts less than 200/microL remained susceptible to opportunistic infections. Treatment interruptions, a poor virologic response, and older age were the major factors negatively affecting the recovery of CD4 T lymphocytes.     

Immunologic and virologic consequences of temporary antiretroviral treatment interruption in clinical practice

To determine the long-term immunologic and virologic effects of antiretroviral treatment interruptions, a retrospective analysis of an ongoing observational database was performed at a university HIV clinic. All patients who began highly active antiretroviral therapy (HAART) after January 1, 1996 and (1) were HAART experienced for >/=90 days, (2) had a treatment interruption (TI) for >/=30 days, (3) resumed HAART for >/=30 days, and (4) had CD4(+) cell counts performed pre- and post-TI were included. Main outcome measures included the following: Immunologic success was defined as a post-TI CD4(+) cell count >90% of the pre-TI CD4(+) cell count (post-TI/pre-TI, >90%). Virologic success was defined as a post-TI viral load (VL) less or equal to twice the pre-TI VL (post-TI/pre-TI, 相似文献   

Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy

OBJECTIVE: To assess hepatitis C virus (HCV) antibody prevalence in the EuroSIDA cohort, along with survival, human immunodeficiency virus (HIV)-1 disease progression, virologic response (plasma HIV-1 RNA load of < 500 copies/mL), and CD4 cell count recovery by HCV serostatus in patients initiating highly active antiretroviral therapy (HAART). RESULTS: HCV serostatus at or before enrollment was available for 5957 patients; 1960 (33%) and 3997 (67%) were HCV seropositive and seronegative, respectively. No association between an increased incidence of acquired immunodeficiency syndrome-defining illnesses or death and HCV serostatus was seen after adjustment for other prognostic risk factors known at baseline (adjusted incidence rate ratio [IRR], 0.97 [95% confidence interval {CI}, 0.81-1.16]). However, there was a large increase in the incidence of liver disease-related deaths in HCV-seropositive patients in adjusted models (IRR, 11.71 [95% CI, 6.42-21.34]). Among 2260 patients of known HCV serostatus initiating HAART, after adjustment, there was no significant difference between HCV-seropositive and -seronegative patients with respect to virologic response (relative hazard [RH], 1.13 [95% CI, 0.84-1.51]) and immunologic response, whether measured as a > or = 50% increase (RH, 0.94 [95% CI, 0.77-1.16]) or a > or = 50 cells/microL increase (RH, 0.92 [95% CI, 0.77-1.11]) in CD4 cell count after HAART initiation. CONCLUSIONS: HCV serostatus did not affect the risk of HIV-1 disease progression, but the risk of liver disease-related deaths was markedly increased in HCV-seropositive patients. The overall virologic and immunologic responses to HAART were not affected by HCV serostatus.     

The naive CD4+ count in HIV-1-infected patients at time of initiation of highly active antiretroviral therapy is strongly associated with the level of immunological recovery

Current antiretroviral therapy can induce considerable, sustained viral suppression followed by immunological recovery, in which naive CD4 + cells are important. Long-term immunological recovery was investigated during the first 3 y of highly active antiretroviral therapy (HAART) in 210 HIV-1-infected patients. The focus was on the naive CD4 + cell time course and associations between naive CD4 + cell counts and established prognostic markers. Total and naive CD4 + cell counts were measured using flow cytometry. The HIV-RNA detection limit was 20 copies/ml. During 36 months of HAART, the total CD4 + count followed a triphasic pattern, reflecting an initial phase of rapid redistribution from lymphoid tissues, followed by a slow increase, partially due to an increase in naive CD4+ cell count. From Month 18 onwards, both naive and total CD4 + cell counts stabilized, although viral suppression was sustained. There was no association between plasma viral load and the increase in naive CD4 + cell count. Importantly, baseline naive CD4 + cell count was significantly associated with the change in naive CD4 + cell count, suggesting that the naive cell count at baseline does influence the immunological recovery that can be obtained from treatment. Surprisingly, the naive CD4 + cell count tended to stabilize at a subnormal level after 18 months of HAART. This finding merits further investigation.     

Comparative response of African HIV-1-infected individuals to highly active antiretroviral therapy

OBJECTIVE: Few data exist on the virological response to antiretroviral therapy of individuals infected with African HIV-1 subtypes. Our objective was to compare the response, in our clinic, of African HIV-1-infected patients with their British and European contemporaries treated with the same regimes. DESIGN: The St Mary's Hospital HIV database was used to identify drug-naive African and European patients starting a highly active antiretroviral therapy (HAART) regimen. METHODS: HIV-1 subtype was determined by phylogenetic analysis of pol sequences. Kaplan-Meier survival analysis was used to estimate the proportion of patients achieving undetectable viral loads (< 500 copies/ml). The longer-term response to therapy was assessed by changes in CD4 cell counts and viral loads from baseline. RESULTS: A total of 265 patients were classified as 'European' and 97 as 'African', confirmed by sequence. The time to first undetectable viral load was similar for the two groups (P = 0.9). Although there were no statistically significant differences in the CD4 cell count responses (P = 0.11), there was evidence of an increase in viral load after 9 months for the African group, resulting in a widening viral load gap between the two cohorts; the effect of ethnic group was statistically significant (P < 0.001). CONCLUSION: The initial virological and immunological responses of the African and European cohorts to HAART were similar; although the longer-term virological response was poorer in the African cohort, which may be related to adherence. On the basis of these findings, there is no justification for withholding HAART from Africa on virological grounds.     

Long-term observation of adolescents initiating HAART therapy: three-year follow-up

The PACTG 381 cohort included 120 adolescents infected via high-risk behaviors and treated with at least two NRTIs plus either a protease inhibitor or an efavirenz-containing HAART regimen. After 24 weeks of therapy, only 69 of 118 (59%) evaluable subjects had undetectable viral loads. We now present findings of the study after 3 years of follow-up. Virologic, immunologic, and treatment information were collected from subjects every 12 weeks beyond the first 24 weeks of therapy through 156 weeks. Of the 120 subjects starting HAART, 44 (37%) stayed on study treatment for the 3 years of observation. Twenty-nine (24%) subjects reached and maintained undetectable viral loads. Poorer adherence (p = 0.016), higher baseline viral load (p = 0.010), and CD8 naive counts (p = 0.034) predicted virologic failure. Immunologic measurements improved from entry to the end of follow-up in the subjects with undetectable viral loads. CD4 counts at the end of study were not significantly different from HIV-uninfected youth, but CD4%, CD8 counts and percent, and CD8 activation markers remained significantly different. Adolescents infected with HIV via high-risk behaviors have less than optimal responses to HAART therapy with only 24% achieving and maintaining undetectable viral loads over 3 years. Immunologic improvement was demonstrated and CD4 counts in subjects with virologic control reached levels in HIV-uninfected adolescents. Interventions, especially those focused on adherence, are necessary to improve HAART outcomes in adolescents.     

Factors associated with poor immunologic response to virologic suppression by highly active antiretroviral therapy in HIV-infected women

Virologic response to highly active antiretroviral therapy (HAART) typically results in a substantial rise in CD4 cell counts. We investigated factors associated with poor CD4 response among HIV-infected women followed at 6-monthly intervals in the Women's Interagency HIV Study. Women with nadir CD4 counts < 350 cells/mm3 who achieved at least 6 months of plasma HIV RNA < 400 copies/ml were studied. Demographic, clinical, and treatment factors were compared between immunologic nonresponders, defined as the lower quartile of CD4 count change after two visits with virologic suppression (< 56 cell/mm3; n = 38), and the remaining group of responders (n = 115). Immunologic nonresponders had lower baseline HIV RNA levels and higher CD4 counts, more frequently used HAART 6 months prior to achieving consistent viral suppression, and more commonly had HIV RNA levels > 80 but < 400 copies/mL at both suppressive visits (21 vs. 7.8%, p = 0.024). In multivariate analysis, higher CD4 count and lower HIV RNA level at the last presuppressive visit were associated with immune nonresponse. We conclude that higher baseline CD4 count and lower HIV RNA level were associated with poor immunologic response to HAART in women with virologic suppression for at least 6 months. Persistent low level viremia may also contribute.     

Long-term evolution of CD4 count in patients with a plasma HIV RNA persistently <500 copies/mL during treatment with antiretroviral drugs

BACKGROUND: The increase in CD4 count may reach a plateau after some duration of virological response to highly active antiretroviral therapy (HAART). METHODS: A total of 1281 HIV-infected patients initiating HAART were enrolled in the AntiPROtease (APROCO) cohort. We investigated determinants of increase in CD4 count using longitudinal mixed models in patients who maintained a plasma HIV RNA <500 HIV-1 RNA copies/mL. RESULTS: A total of 870 patients had a virological response at month 4. The median follow-up time was 57 months. Mean estimated increases in CD4 count in patients with persistent virological response were 29.9 cells/muL/month before month 4, 6.4 cells/microL/month between months 4 and 36, and 0.7 cells/microL/month (not significantly different from 0) after month 36. Three factors were associated with a significantly positive CD4 count slope after month 36: male gender (+0.9), no history of antiretroviral therapy at baseline (+1.7) and baseline CD4 count <100 cells/microL (+2.6). In patients who maintained a virological response after 5 years of HAART, a CD4 count >500 cells/microL was achieved in 83% of those with a baseline CD4 count >or=200 cells/microL and in 45% of those with a baseline CD4 count <200 cells/microL. CONCLUSION: The increase in CD4 count reaches a plateau after 3 years of virological response. Even if patients initiating HAART with low CD4 counts still show a CD4 count increase after 3 years, it remains insufficient to overcome immune deficiency in all patients.     

Effect of highly active antiretroviral therapy on cervicovaginal HIV-1 RNA

OBJECTIVES: To determine the frequency of cervicovaginal lavage and plasma HIV-1 RNA levels that are below detectable levels (< 400 copies/ml) among women on highly active antiretroviral therapy (HAART), non-HAART and on no therapy. To compare the effect of initiating HAART on the timing of HIV-1 RNA suppression in the blood plasma and genital tract among antiretroviral-na?ve women. METHODS: Data were obtained from 205 HIV-infected women with paired plasma and cervicovaginal lavage viral load measurements. Seven antiretroviral-na?ve women starting HAART had viral load measurements performed daily for one week, at 2 weeks and at 1 month after initiating therapy. Viral load quantification was carried out by nucleic acid sequence-based amplification assay. The lower limit of detection was 400 copies/ml. RESULTS: Plasma and cervicovaginal HIV-1 RNA was detectable in 71 and 26% of the women, respectively. Among women with plasma viral loads less than 400, 400-9999, and 10,000 copies/ml or over, genital tract HIV-1 RNA was detected in 3, 17 and 48%, respectively (P < 0.001). Fifty-one per cent of the women with CD4 cell counts of less than 200/mm3 had detectable cervicovaginal viral loads compared with 18% among women with CD4 cell counts of 200/mm3 or over (P < 0.001). Cervicovaginal HIV-1 RNA was less than 400 copies/ml in 85% of those on HAART, 69% of those on non-HAART and 69% of those on no therapy (P < 0.045). In seven antiretroviral-na?ve women initiating HAART, cervicovaginal HIV-1 RNA decreased by 0.7-2.1 log10 within 1-14 days of starting therapy. CONCLUSION: The cervicovaginal HIV-1 RNA level was positively correlated with plasma HIV-1 RNA and negatively with the CD4 cell count. The use of HAART was significantly associated with below-detectable levels of HIV-1 RNA in both plasma and the genital tract. HIV-1 RNA suppression in the genital tract may occur rapidly after initiating therapy.