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PubMed2003

Clinical and immunologic progression in HIV-infected US women before and after the introduction of highly active antiretroviral therapy.

OBJECTIVE: To examine factors associated with clinical and immunologic HIV disease progression in a cohort of US women. DESIGN: Analysis of data from a prospective, longitudinal, case-control study of HIV-infected women followed every 6 months for 7 years. SETTING: Four urban clinical centers in the United States. PARTICIPANTS: 648 HIV-infected women who did not have AIDS at time of entry into the study. MEASUREMENTS: Structured clinical and behavioral interviews; protocol-directed physical examinations; CD4 lymphocyte counts; plasma HIV RNA; infectious pathogen serologies. RESULTS With 2304 women-years of follow-up, 46.1% of the women developed AIDS; however, 93.3% of the diagnoses were based on CD4 counts dropping to <200 cells/mm(3). Only 10.6% of the women with CD4 counts <200 cells/mm(3) developed an opportunistic infection. Baseline CD4 count was the strongest predictor of subsequent clinical progression. Illicit substance use, multiple pregnancies, demographic variables, and other infections were not associated with progression. Among women with CD4 counts >500 cells/mm(3) at baseline, those who were anemic or had hepatitis C were more likely to progress to AIDS. By the end of the study, only 52% of the participants were on highly active antiretroviral therapy (HAART). CONCLUSIONS: Despite underutilization of HAART in this multicenter cohort of urban women, opportunistic infections were uncommon, despite CD4 declines.

AIDS-Related Opportunistic Infections↗

PubMed1998

Effects of IL-2 therapy in asymptomatic HIV-infected individuals on proliferative responses to mitogens, recall antigens and HIV-related antigens.

The effects of IL-2 therapy on lymphoproliferative responses to mitogens, recall antigens and HIV epitopes were studied in asymptomatic HIV-infected patients enrolled in a phase II study of intermittent continuous intravenous (Ci.v.) IL-2 and subcutaneous infusions of polyethylene glycol-modified (PEG) IL-2. Sixteen consecutive patients randomized to receive Ci.v. IL-2 (n = 5), PEG IL-2 (n = 7) or anti-viral therapy alone (n = 4) were studied. All patients were vaccinated with tetanus toxoid (TT) before receiving therapy. Proliferative responses to phytohaemagglutinin (PHA), soluble anti-CD3, TT, streptokinase/streptodornase (SK/SD) and 11 previously described HIV-specific T-helper epitopes from gag and env were studied at weeks 0, 16, 30 and 48. Median CD4+ lymphocyte increases of 272 and 255CD4+ cells/microl were observed in the Ci.v. IL-2 and PEG IL-2 groups at week 48, while decreasing by 104 cells/microl in the anti-retroviral therapy alone group. At each time point proliferative responses to PHA, anti-CD3, TT and SK/SD were not different between treatment arms. Similarly, no differences in responses to HIV epitopes were found between the groups and no new responses to HIV epitopes were detected. IL-2 therapy results in a significant increase in peripheral blood CD4+ lymphocyte count, but this increase is not associated with quantifiable improvements in lymphoproliferative responses to mitogens, recall or HIV antigens.

Adult↗

PubMed1995

Relationship of oral disease to the presence of cytomegalovirus DNA in the saliva of AIDS patients.

Cytomegalovirus is an important pathogen in persons infected with human immunodeficiency virus. In this study a thorough oral examination was done and blood and urine cultures for cytomegalovirus were obtained from a group of 31 patients with acquired immunodeficiency syndrome with CD4 lymphocyte counts less than 150 cells/mm3. Whole saliva was also collected for detection of cytomegalovirus deoxyribonucleic acid (DNA) via the polymerase chain reaction. The presence of cytomegalovirus DNA in the saliva specimens was not related to the presence of cytomegalovirus in the urine, which suggests a local source of cytomegalovirus from salivary gland and kidney parenchyma. There was also a strong statistical relationship between salivary cytomegalovirus DNA and xerostomia (p = 0.0004), which suggests that cytomegalovirus may be a cause of salivary gland dysfunction in patients with acquired immunodeficiency syndrome with low CD4 counts.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Effect of hormonal contraceptive use on plasma HIV-1-RNA levels among HIV-infected women.

We compared the HIV-1-RNA and CD4 lymphocyte counts from users and non-users of hormonal contraception cross-sectionally upon entry into the Women's Interagency HIV Study, and again longitudinally. There did not appear to be an association between hormonal contraception use and HIV-1-RNA levels in our study. There was a small increase in CD4 cell counts among hormonal users of doubtful clinical significance.

Adult↗

PubMed2004

Antibodies reactive with C-terminus of the second conserved region of HIV-1gp120 as possible prognostic marker and therapeutic agent for HIV disease.

It has been reported that antibodies reactive with peptide RSANFTDNAKTIIVQLNQSVEIN (peptide NTM) derived from the C-terminus of the second conserved domain of HIV-1 envelope glycoprotein gp120 could represent an important factor in control of the HIV disease. In order to check this notion we (i) tested reactivity with peptide NTM serum samples collected from 310 consecutive HIV-1 infected patients with a CD4(+) lymphocyte count ranging from 10 to 800/microL and (ii) performed the longitudinal study that included 107 sera samples collected from 29 HIV patients. Results of these studies demonstrated correlation between presence of anti-NTM antibodies in sera of HIV patients and disease progression measured by the CD4(+) cell count. Based on these findings we proposed the anti-NTM antibodies as useful prognostic marker for HIV disease.

Biomarkers↗

PubMed1999

Therapeutic immunisation with recombinant gp160 in HIV-1 infection: a randomised double-blind placebo-controlled trial. Nordic VAC-04 Study Group.

BACKGROUND: The immune system's ability to scavenge and destroy detrimental HIV-1 products has an important effect on virion production and the course of infection. In earlier trials of therapeutic immunisation with envelope protein recombinant gp160 (rgp160) we observed a transient positive effect on CD4-lymphocyte counts. This randomised placebo-controlled study investigated whether our preliminary findings represented a potential for a more benign clinical course. METHODS: 835 HIV-seropositive patients from 20 centres in Sweden, Norway, and Finland with CD4-cell counts above 200/microL were randomly assigned to receive 160 microg rgp160 or placebo (alum adjuvant alone) every 3 months for 3 years after an induction period, as well as optimum available treatment. Analyses were by intention to treat. FINDINGS: 63 of 416 vaccine-group patients and 61 of 419 placebo-group patients reached a primary clinical endpoint (AIDS-defining event or death); the time to first clinical endpoint did not differ between the groups (p=0.864). Significantly fewer vaccine-group patients than placebo-group patients reached the primary immunological endpoint of a decrease of more than 30% from baseline CD4-cell count (157 vs 189, p=0.03). A higher proportion of the vaccine group had CD4-cell counts higher than baseline at 6 months (167 vs 133, p=0.014). HIV-1-specific T-cell immune reactivity was induced in all vaccine recipients studied. No severe adverse events associated with the vaccine were noted during the study. There were significantly fewer deaths among the vaccine recipients than among the placebo-group patients at 2 years, but not at the end of the study. INTERPRETATION: Therapeutic immunisations with rgp160 have a modest effect on CD4-cell counts, but this treatment alone did not lead to clinical benefit when given in addition to best clinical practice at the time of the trial. Immunisation in conjunction with antiretroviral therapy was also effective, which strongly suggests that a combination with highly active therapy would improve the total effect.

AIDS Vaccines↗

PubMed2005

Prevention of cryptococcosis in HIV-infected patients with limited access to highly active antiretroviral therapy: evidence for primary azole prophylaxis.

Despite advances in the treatment of HIV disease, the incidence and mortality of invasive cryptococcal disease remain significant. A matched, case-control study was performed to examine the impact of highly active antiretroviral therapy (HAART) and azole use on the incidence of invasive cryptococcal disease in HIV-infected patients. The study was performed at a metropolitan hospital with a large indigent population and an incidence of seven cases of cryptococcal disease per 1000 persons with AIDS. Bivariate analysis, matched on CD4 count, revealed that both HAART use [odds ratio (OR) 0.43; 95% confidence interval (CI) 0.23-0.99] and azole use (OR 0.14; 95% CI 0.06-0.34) had a protective effect. Conditional logistic regression stratified on CD4 lymphocyte count revealed a protective role for azole use (OR 0.15; 95% CI 0.06-0.40) but not for HAART use (OR 0.47; 95% CI 0.18-1.26). Of note, the prevalence of HAART use was low in both cases and controls, with only 12% of cases and 23% of controls on HAART. The results of this study support previous evidence that azole use prevents invasive cryptococcal disease. Although current guidelines for the prophylaxis of opportunistic infections do not suggest routine prophylaxis for cryptococcal infection, this issue should be reconsidered, especially in populations that have a low prevalence of HAART use.

AIDS-Related Opportunistic Infections↗

PubMed2001

Improving the fit of bivariate smoothing splines when estimating longitudinal immunological and virological markers in HIV patients with individual antiretroviral treatment strategies.

CD4+ lymphocyte count and HIV RNA plasma viral load are longitudinally monitored in patients with HIV infection. Because data collection intervals may be unequally spaced and these markers experience high within-patient variability, they may be smoothed before use in subsequent models. Estimation strategies must be able to accommodate the drastic changes in viral load which may occur when an individual's treatment strategy is updated. Because these treatment changes are not regimented, these dynamics cannot be modelled using standard methods. We propose univariate and bivariate cubic smoothing splines to fit CD4+ count and viral load over time. The method is developed using state space equations, and the Kalman filter is used to calculate the log-likelihood. Non-linear optimization is used to obtain the maximum likelihood estimates. A modification of the Kalman filter allows non-informative or diffuse priors at the initial observation. Since treatment changes are expected to alter the shape of the curve, we further extend the Kalman filter to permit greater flexibility in the smoothing spline at these time points. The method produces smoothed estimates of the viral load and CD4+ count curves over time.

Anti-HIV Agents↗

PubMed2000

Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men.

Standard methods for survival analysis, such as the time-dependent Cox model, may produce biased effect estimates when there exist time-dependent confounders that are themselves affected by previous treatment or exposure. Marginal structural models are a new class of causal models the parameters of which are estimated through inverse-probability-of-treatment weighting; these models allow for appropriate adjustment for confounding. We describe the marginal structural Cox proportional hazards model and use it to estimate the causal effect of zidovudine on the survival of human immunodeficiency virus-positive men participating in the Multicenter AIDS Cohort Study. In this study, CD4 lymphocyte count is both a time-dependent confounder of the causal effect of zidovudine on survival and is affected by past zidovudine treatment. The crude mortality rate ratio (95% confidence interval) for zidovudine was 3.6 (3.0-4.3), which reflects the presence of confounding. After controlling for baseline CD4 count and other baseline covariates using standard methods, the mortality rate ratio decreased to 2.3 (1.9-2.8). Using a marginal structural Cox model to control further for time-dependent confounding due to CD4 count and other time-dependent covariates, the mortality rate ratio was 0.7 (95% conservative confidence interval = 0.6-1.0). We compare marginal structural models with previously proposed causal methods.

Anti-HIV Agents↗

PubMed1996

The role of immunologic and viral markers in predicting clinical outcome in HIV infection.

OBJECTIVE: In an ideal world, one clinical marker would explain all the variance in a disease system. In reality, however, this is rarely the case and HIV disease is no exception. This review considers several specific markers that have demonstrated some use in clinical trials and/or epidemiologic studies of antiretroviral therapy. DISCUSSION: CD4 lymphocyte count, HIV viral load and perhaps immune activation markers can be used to measure the activity of antiretroviral therapy. Some recent studies are presented and the results discussed. CONCLUSION: Sustained improvements in several markers (particularly HIV viral load and CD4 cell count) in combination appear to be the most predictive of clinical benefit. No current viral or immunologic markers adequately reflect toxicities attributable to antiretroviral therapy. Lamivudine/zidovudine combination therapy leads to sustained changes in several markers, and appears to be well tolerated. This may translate into significant clinical benefit but the duration of such benefit remains unknown.

Biomarkers↗

PubMed1993

CD4+ lymphocyte level and rate of decline as predictors of AIDS in intravenous drug users with HIV infection.

OBJECTIVE: To examine the relationship between rate of loss of CD4+ T lymphocytes and risk of AIDS in HIV-infected intravenous drug users (IVDU) enrolled in a methadone program in the Bronx, New York. DESIGN: Serial CD4 percentages (CD4%) among lymphocytes before AIDS diagnosis were recorded at approximately 6-month intervals for 190 HIV-antibody-positive subjects. METHODS: A nested case-control study was performed, in which all subjects who developed AIDS were compared with those who remained AIDS-free. The relationship between CD4% decline and AIDS risk was evaluated using proportional-hazards regression. RESULTS: Analyses that used a single baseline CD4% measurement to adjust for CD4+ lymphocyte count suggested that both low (1-5 CD4% per semester) and high (> 5 CD4% per semester) rates of decline might be related to AIDS risk: relative risks were 1.83 and 1.44, although the 95% confidence intervals (Cl) included 1.0 in each case. Adjustment for current level of CD4% eliminated the association between low rates of CD4% decline and AIDS risk, but not that between high rates of decline and AIDS risk (adjusted relative risk, 1.80; 95% Cl, 0.57-5.70). Serial observations showed that a rate of decline of CD4% > 5 per semester was a significant predictor of AIDS risk after controlling for level of CD4% achieved (adjusted relative risk, 3.58; 95% Cl, 1.07-11.95). CONCLUSIONS: IVDU who develop AIDS have a greater rate of CD4 cell loss than subjects who remain AIDS-free. A low rate of CD4+ lymphocyte depletion is not an important predictor of the immediate onset of AIDS in HIV-infected IVDU, compared with CD4+ lymphocyte level, but a high rate of CD4+ decline can be.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Joint effects of HIV-1 RNA levels and CD4 lymphocyte cells on the risk of specific opportunistic infections.

OBJECTIVES: To evaluate the predictive value of baseline plasma HIV-1 RNA levels and CD4 lymphocyte counts and early changes in these markers after initiating antiretroviral therapy on the risk of development of specific opportunistic infections (OIs). DESIGN: Patient data from four antiretroviral therapy studies were combined for a retrospective analysis. The analysis included 842 participants from the virology substudies of these trials who had baseline measurements for both HIV-1 RNA levels and CD4 cell counts. METHODS: Cox proportional hazards models were used to assess the joint effects of baseline CD4 cell count and HIV-1 RNA level and early treatment-associated changes in these values on the risk of development of Pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV), or Mycobacterium avium complex (MAC). The effects of potential confounders such as prior prophylaxis and previous OIs were also addressed. RESULTS: Baseline CD4 cell counts and HIV-1 RNA measurements showed significant associations with the risk of PCP, CMV, and MAC. Patients with higher levels of HIV-1 RNA were estimated to have three to six times the risk of these OIs than those with lower levels. Reductions in viral load were linked to significantly reduced risks of PCP, CMV, and MAC. Early decreases in RNA were generally more predictive of risk than were early increases in CD4 cell counts. CONCLUSIONS: Baseline viral load and reductions in viral load during therapy appeared to influence the risk of these OIs independently of the CD4 cell count. Future guidelines for the initiation of prophylaxis for these OIs may be improved by incorporating information on viral load.

AIDS-Related Opportunistic Infections↗

PubMed1994

Factors associated with initiation of primary medical care for HIV-infected persons.

PURPOSE: To examine the degree of immune dysfunction of human immunodeficiency virus (HIV)-infected patients at the time of presentation and to identify factors associated with early and late initial primary medical care for HIV infection as measured by CD4+ lymphocyte count. PATIENTS AND METHODS: Two hundred fifty-one consecutive outpatients without prior primary care for HIV infection were assessed at a municipal hospital HIV intake clinic (derivation group). Sociodemographic and clinical variables were examined for their association with CD4+ cell count on presentation in bivariate and stepwise linear regression analyses. Variables of interest were examined in 123 similar patients at a second site to assess the generalizability of our findings (validation group). RESULTS: In the derivation group, 30% of patients presented for initial primary care with CD4+ cell counts less than 200/mm3, 51% had counts from 201/mm3 to 500/mm3, and only 19% had counts greater than 500/mm3. Twenty-seven percent of patients had delayed seeking medical care for longer than 1 year and 12%, for more than 2 years after an initial positive HIV serologic evaluation. Three variables were significant and independent predictors of CD4+ cell count on presentation: Haitian ethnicity (P = 0.05) and HIV-related symptoms (P = 0.005) were associated with lower CD4+ cell counts; and female sex (P = 0.009) was associated with higher CD4+ cell counts. With HIV-related symptoms excluded from the model, a history of cocaine use was also a significant predictor for higher CD4+ cell count (P = 0.02). In the validation group, which included few Haitians, results for female sex and HIV-related symptoms showed a similar association. CONCLUSIONS: Most HIV-infected patients presented for primary care with advanced immune dysfunction. A substantial percentage of patients waited over a year to initiate medical care after testing positive for HIV. Haitian patients presented later for primary HIV care as measured by CD4+ cell count. Women presented with significantly higher CD4+ cell counts than did men. Since few characteristics examined could clearly identify the majority of late-presenting HIV-infected patients, improved general and targeted efforts are needed to link all HIV-infected people with primary medical care before the development of advanced disease.

Adult↗

PubMed1999

The value of patient-reported adherence to antiretroviral therapy in predicting virologic and immunologic response. California Collaborative Treatment Group.

OBJECTIVE: To correlate self-reported antiretroviral adherence with virologic suppression. DESIGN: Prospective observational study of adherence to therapy nested in a randomized comparative trial of frequent versus infrequent monitoring of plasma HIV RNA. SETTING: Five university-affiliated HIV clinics. PATIENTS: A group of 173 HIV-infected patients with a mean baseline CD4 count of 142 x 10(6) cells/l (range 3-515) of whom 164 and 119 completed adherence questionnaires at 2 and 6 months, respectively. INTERVENTION: Individualized, unrestricted antiretroviral therapy. MEASUREMENTS: Patients were classified into four groups by adherence to therapy in the previous 4 weeks (< 80%, 80-95%, 95-99%, 100%). Plasma HIV RNA levels and CD4 lymphocyte counts were measured bimonthly. RESULTS: Recreational drug or alcohol use was associated with decreased adherence, whereas frequency of HIV RNA monitoring, demographic variables, (age, gender, education, and risk group) and stage of disease had no effect. Greater HIV suppression at 6 months was seen across four categories of increasing adherence (P = 0.009 for linear trend). Patients reporting < 80% adherence at 6 months had a 0.2 log10 copies/ml increase in HIV RNA and a loss of 19 x 10(6) CD4 cells/l compared with a 1.1 log10 copies/ml decrease in HIV RNA and an increase of 72 x 10(6) CD4 cells/l in those reporting 100% adherence (P = 0.02). CONCLUSION: Self-reported poor adherence (< 80%) and drug or alcohol use predicted non-response of HIV RNA at 6 months of antiretroviral therapy.

Adult↗

PubMed1995

Controversies in anti-retroviral therapy of adults.

Much controversy surrounds the use of antiretroviral drugs in HIV-infected patients. The many studies involving large numbers of patients that have been and are being conducted have raised as many questions as they have sought to answer. Given that no cure exists and that all clinically available drugs have only limited activity despite their high toxicity, the question of which drug (or combination of drugs) to use, and in whom, continues to vex both the clinician and the patient. Only three specific antiretroviral agents are currently licensed for use: zidovudine (ZDV), didanosine (dideoxyinosine, ddI) and zalcitabine (dideoxycytidine, ddC). This article reviews the major studies comparing the clinical efficacy of these drugs and the possible benefits of adding acyclovir to zidovudine therapy. The questions of when to begin antiretroviral therapy and the role of combination chemotherapy are discussed. Whenever possible, 'clinical' endpoints (death or clinical progression) are distinguished from 'softer' endpoints (surrogate markers of progression, such as the CD4 lymphocyte count) in the studies reviewed. Recommendations for the use of antiretroviral agents based on currently available published data are made.

AIDS-Related Complex↗

PubMed2004

HIV infection in the era of highly active antiretroviral therapy: the Malaga Study.

We analyse the characteristics of patients diagnosed with HIV infection in the highly active antiretroviral therapy era in the southeast of Spain. Data were collected on 470 HIV patients diagnosed between January 1997 and December 2002. The number of cases fell over recent years and HIV transmission was sexual in 70.5%. The mean CD4 lymphocyte count was 302.1 x 10(6)/L and the mean viral load 4.70 log(10). Diagnosis of HIV coincided with an AIDS-defining opportunistic illness in 30.6% of patients and a late diagnosis (CD4 < 200 x 10(6)/L) was made in 48.3% of patients. A late diagnosis was related to male gender (OR 2.50; 95% CI 1.20-5.12; P < 0.001) and AIDS case (OR 18.80; 95% CI 10.50-33.80; P < 0.00001). These results suggest that there has been a progressive reduction in new cases of HIV-infected patients, with the main route of transmission being sexual and that the diagnosis was late in almost half the patients.

Adult↗

PubMed1999

Cystoid macular oedema and cytomegalovirus retinitis in patients with HIV disease treated with highly active antiretroviral therapy.

BACKGROUND: Although cystoid macular oedema (CMO) is a rare cause of visual loss in AIDS related cytomegalovirus (CMV) retinitis, nine cases are reported of CMO occurring in HIV infected patients with a prior diagnosis of CMV who were receiving highly active antiretroviral therapy (HAART). METHODS: Medical and ophthalmological records of nine AIDS patients with inactive CMV retinitis were retrospectively analysed. Ophthalmic examination data, laboratory findings, and the systemic antiviral treatment were studied. Ophthalmic examination included visual acuity, anterior chamber flare measured with the laser flare cell meter (LCFM), vitreous haze quantification according to the Nussenblatt grading system, and fluorescein angiography. RESULTS: Nine HIV infected patients, eight men and one woman, mean age 39 years (range 29-53 years) presented with inactive CMV retinitis and CMO. On fluorescein angiography, CMO was present only in eyes (14 eyes) with signs of previous CMV retinitis. CMV retinitis was inactive in all of them. Visual acuity ranged from 20/200 to 20/30. In 10 eyes with CMV retinitis, anterior chamber flare measured with the LCFM ranged from 18.5 to 82 photons/ms (mean 35.42 ph/ms). A significant vitreous inflammation (1.5+) was observed in eight eyes. All patients had been treated with anti-CMV drugs for a mean period of 18 months (range 12-36 months). All nine patients received HAART with a combination of two nucleotide analogue reverse transcriptase inhibitors and one protease inhibitor for a mean period of 14 months (range 9-18 months). The HIV viral load was below detectable levels (< 200 copies/ml) in eight patients and low (3215 copies/ml) in one. At the time of CMO, the median CD4+ lymphocyte count was 232 cells x 10(6)/l (range 99-639). CONCLUSION: In AIDS patients, the usual absence of intraocular inflammation in eyes affected by CMV retinitis has been tentatively explained by the profound cellular immunodeficiency. In these patients, treated with HAART, CD4+ counts were increased for several months (mean 14 months). In their eyes, CMV retinitis was associated with significant ocular inflammation and CMO. These findings could be related to the restoration of immune competence after HAART as recently shown.

AIDS-Related Opportunistic Infections↗

PubMed1999

Impact of early HIV-1 RNA and T-lymphocyte dynamics during primary HIV-1 infection on the subsequent course of HIV-1 RNA levels and CD4+ T-lymphocyte counts in the first year of HIV-1 infection. Sydney Primary HIV Infection Study Group.

Plasma HIV-1 RNA and CD4+ T-cell counts after HIV-1 seroconversion are important independent markers that predict the clinical course of HIV-1 infection. The prognostic significance of these parameters during primary HIV-1 infection, however, remains largely unknown. In a cohort of 53 male study subjects (age, 33 +/- 7 years), who consecutively presented with primary HIV-1 infection, we analyzed the relationship between early plasma HIV-1 RNA, CD4+ and CD8+ T-cell counts, beta2-microglobulin, and p24-antigen levels determined in the first 3 months and subsequent plasma HIV-1 RNA levels and CD4+ T-cell counts 6 to 12 months after onset of primary symptoms. Peak, nadir, and median HIV-1 RNA levels in the first 30 days were already significantly associated with HIV-1 RNA levels at 6 to 12 months (p = .02, p < .0001, and p = .01, respectively). Similarly, early nadir and median CD4+ T-lymphocyte counts in the first 30 days showed a significant relationship with CD4+ T-cell counts at 6 to 12 months (p = .009 and p = .0008, respectively). Study subjects with an early decline of CD4+ counts to <500 cells/microl had an eightfold higher risk that CD4+ counts were <500 cells/microl at 1 year. Of all evaluated virologic parameters, only nadir HIV-1 RNA at 76 days predicted CD4+ counts at 6 to 12 months (p = .006). Early HIV-1 RNA levels and CD4+ counts are already associated with the time course of those parameters 6 to 12 months after onset of symptoms. Nadir viral load was the strongest predictor of HIV-1 RNA levels as well as of CD4+ counts at 6 to 12 months. An early decline of CD4+ T lymphocytes may be a useful clinical prognostic marker for rapid disease progression.

Adult↗