First Year Of Highly Active Antiretroviral Therapy Research Articles

Iron status among HIV-infected adults during the first year of antiretroviral therapy in Tanzania.

The influence of inflammation on iron status among people living with HIV (PLWHIV) has not been well explored. We evaluated the trajectory of iron status among PLWHIV during the first year of highly active antiretroviral therapy (HAART), compared alternative approaches for inflammation correction, and assessed the associations of iron status with HIV-1 viral load and anthropometric outcomes. We conducted a secondary analysis of data from a randomized trial among 400 adults initiating HAART in Tanzania. Ferritin and C-reactive protein (CRP) were measured at baseline, 1, 6 or 12 months. Ferritin was considered in four ways: unadjusted, and adjusted for inflammation using higher cut-off (HC), Thurnham-corrected (TC) and regression-corrected (RC) approaches. For unadjusted, TC and RC ferritin, iron deficiency (ID) was defined using ferritin < 15 μg/L and elevated iron status was defined using ferritin > 150 μg/L among females and > 200 μg/L among males. For HC ferritin, elevated iron status was defined based on serum ferritin > 500 μg/L, while ID was defined using ferritin < 70 μg/L in the presence of inflammation and < 15 μg/L in the absence of inflammation. Regression models evaluated the trajectory of ferritin concentration across categories of baseline characteristics, and assessed the association of iron status with viral and anthropometric outcomes. The prevalence of iron deficiency at HAART initiation was 9% for unadjusted, 17% for HC, 12% for TC and 22% for RC ferritin. The prevalence of elevated iron status was 42% for unadjusted, 18% for HC, 31% for TC, and 15% for RC ferritin. The prevalence of iron deficiency for all three methods increased during the first year of HAART, while the prevalence of elevated iron status decreased. Baseline elevated iron status defined using HC ferritin was associated with a greater risk of HIV-1 viral load > 1000 copies/mL [relative risk (RR)= 4.29, 95% CI: 1.38-13.3] and incidence of being underweight [body mass index (BMI) < 18.5kg/m2 , hazard ratio (HR)= 3.65, 95% confidence interval (CI): 1.38-9.67]. Neither baseline-elevated iron status defined using TC or RC ferritin nor baseline iron deficiency defined using any of the three methods was associated with HIV-1 viral load or anthropometric outcomes. Whether and how inflammation correction is done influences findings of studies of iron status among PLWHIV.

Dynamics of T-cell subsets and their relationship with oral and systemic opportunistic infections in HIV/AIDS patients during the first year of HAART in Guangxi, China.

To analyze the dynamic changes in Th1, Th2, Tc1, and Tc2 of HIV/AIDS patients during the first year of highly active antiretroviral therapy (HAART) and to explore their relationship with oral and systemic opportunistic infections, a cohort study was carried out among HIV/AIDS patients in Guangxi, China. Ninety HIV/AIDS patients and 30 healthy controls (HC) were included. The enrolled HIV/AIDS patients were examined at baseline and after 3, 6, and 12 months of HAART. On each visit, oral and systemic opportunistic infections were recorded, oral Candida load and plasma viral load (VL) were counted, differential T-cell counts and flow cytometric analysis of T-cell subsets were performed. During the first year of HAART, the total number of opportunistic infections decreased steadily with the change in oral candidiasis (OC) most representatively. A significant Th1→Th2 switch (Th1/Th2 ratio 0.23 ± 0.12, HC 1.45 ± 0.38) and slight Tc1→Tc2 shift (Tc1/Tc2 ratio 0.93 ± 0.29, HC 1.13 ± 0.33) were found at baseline, and both received slow mitigation after HAART. LgCFU and clinical OC were correlated positively with both LgVL and clinical stage (P < 0.05) at baseline. LgCFU was also correlated positively with clinical stage at all four time points (P < 0.05). In multiple factor analysis, Th1 was confirmed to be correlated negatively with LgVL (Std.B = -0.295, P = 0.025) and LgCFU (Std.B = -0.227, P < 0.001) at baseline. After HAART, LgCFU and clinical stage were only correlated negatively with CD4 when all factors were included. These results suggest that oral candidiasis and oral Candida load could be useful clinical markers in the evaluation of HIV/AIDS patients. Th1 may play an important role against oral and systemic opportunistic infections. Tc1 and Tc2 both showed positive roles in the control of viremia without HAART. J. Med. Virol. 87:1158-1167, 2015. © 2015 Wiley Periodicals, Inc.

Dynamic analysis of oral Candida carriage, distribution, and antifungal susceptibility in HIV‐infected patients during the first year of highly active antiretroviral therapy in Guangxi, China

Highly active antiretroviral therapy (HAART) as an effective therapy for immune reconstruction among patients with HIV/AIDS might have influence on oral Candida status. We investigated oral Candida carriage, distribution, and antifungal susceptibility dynamically during the first year of HAART among adult HIV-infected patients in Guangxi, China. Forty-five adult HIV-infected patients who received their first year HAART in the AIDS clinic of the Guangxi Center for Disease Control (CDC) and 31 healthy individuals were recruited. Clinical information and oral examinations were obtained. Oral rinses taken from patients at baseline, 3, 6, 12 months during HAART, respectively, were cultured, and Candida species were identified following standard microbiological techniques. In vitro antifungal susceptibilities were tested by the broth microdilution method. The oral Candida load decreased gradually in the 45 patients with HIV/AIDS during the first year of HAART (P < 0.050). Among 176 Candida isolates, Candida albicans (114/176) was the predominant species, and Candida parapsilosis (23/62) was the most common non-albicans species. We found the frequency of resistance to fluconazole and itraconazole of Candida isolated from our samples increased (P < 0.05) after 12 months of HAART. In addition, the frequency of C. albicans isolates resistant to fluconazole and itraconazole was on the rise (P < 0.05). The Candida load decreased with increased CD4(+) T cell counts, and C. albicans was still the prevailing species. Further, a trend toward more frequent in vitro resistance to fluconazole and itraconazole was observed. Our results provide reference for treatment and prevention of oral candidiasis among this population.

Cumulative Viral Load and Virologic Decay Patterns after Antiretroviral Therapy in HIV-Infected Subjects Influence CD4 Recovery and AIDS

BackgroundThe impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown.Methods and FindingsThree virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U.S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56–3.62, p<0.001). Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001) and overall gain (p<0.05). Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall), in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/µL; p = 0.001) even after adjusting for potential confounders.ConclusionsIn a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution.

Higher Risk of Severe Drug-Induced Liver Injury among Hispanic HIV-Infected Patients after Initiation of Highly Active Antiretroviral Therapy

Little is known about differences across ethnicities in the development of drug-induced liver injury (DILI) after highly active antiretroviral therapy (HAART) initiation. This is a retrospective, longitudinal, comparative, pilot study. DILI within the first year of HAART was evaluated in 50 HIV-infected Hispanics without viral hepatitis who initiated HAART between 2000 and 2009. It was compared to white and black patients (1:1:1) matched by age and CD4 counts. HAART-related DILI of any grade occurred in 30 of 150 (20%) patients and was associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) use (OR 4.49 [95%CI 1.5-13.8]). Severe DILI was significantly more frequent among Hispanics compared to other groups (6% vs. 0%; P = .04). Of the 3 patients with severe DILI, 2 underwent liver imaging and had hepatic steatosis. Severe DILI within the first year of HAART initiation was infrequent and restricted to Hispanics. Additional studies are needed to determine if fatty liver is involved in the excess of severe DILI observed in this group.

Comparison of 3-Drug Versus 4-Drug and PI Versus Non-PI Combinations as Initial HAART: Experience From 1998 to 2007

Although established in controlled studies that there is no advantage to 4-drug highly active antiretroviral therapy (HAART) or regimens with or without protease inhibitors (PIs), we questioned this finding in a clinical setting (ie, no inclusion criteria). Ours is a single clinic retrospective study including all participants >18 years of age during their first year of HAART. A total of 190 participants were reviewed, with 168 (88%) attaining a viral load <400 copies/mL at the end of a year of HAART; 144 of 164 (88%) succeeded with 3 drugs and 24 of 26 (92%) with 4 drugs (P = .51). In all, 59 of 71 (83%) succeeded using a PI versus 109 of 119 (92%) without a PI (P = .08). Male gender and exposure time to HAART were significant variables for a successful outcome. Failures were due to side effects (50%), nonadherence (45%), and drug allergy (5%). Our results support current guidelines recommending 3-drug HAART.

Reduced morbidity and mortality in the first year after initiating highly active anti‐retroviral therapy (HAART) among Ugandan adults

To evaluate the effect of highly active anti-retroviral therapy (HAART) and cotrimoxazole prophylaxis on morbidity after HAART eligibility. Between 1999 and 2006, we collected morbidity data from a community-based cohort of HAART-eligible patients, comparing patients initiating HAART and those non-HAART. Patients aged 15 years or older visited the clinic every 6 months and when ill. Baseline data on patients' characteristics, WHO stage, haemoglobin and CD4+ T-cell counts, along with follow-up data on morbidity (new, recurrent and drug-related), were collected for the first year after initiating HAART or becoming HAART-eligible. We estimated the overall effect of HAART on morbidity; adjusted for the effect of cotrimoxazole prophylaxis by Mantel-Haenszel methods. A negative binomial regression model was used to assess rate ratios (RR) after adjustment for other confounders, including cotrimoxazole. A total of 219 HAART patients (median age 37 years; 73% women; 82% using cotrimoxazole prophylaxis, median haemoglobin 11.7 g/dl and median CD4+ 131 cells/microl) experienced 94 events in 127 person-years. 616 non-HAART patients (median age 33 years; 70% women; 26% using cotrimoxazole prophylaxis, median haemoglobin 11.2 g/dl and median CD4+ 130 cells/microl) experienced 862 events in 474 person-years. The overall morbidity during the first year of HAART was 80% lower than among non-HAART patients (adjusted RR = 0.20, 95% CI: 0.12-0.34). Cotrimoxazole prophylaxis also reduced morbidity (adjusted RR = 0.65, 95% CI: 0.45-0.94). These results confirm the reduction in morbidity due to HAART, and the additional protection of cotrimoxazole prophylaxis.

Quality of life and the impact of drug toxicities in a South African community-based antiretroviral programme.

BackgroundThe impact of highly active antiretroviral therapy (HAART) on health-related quality of life has been widely researched in the developed world, but there are few data from sub-Saharan Africa, where the vast majority of HIV-infected individuals live. This study examined health-related quality of life among HIV-positive individuals initiating HAART in Cape Town, South Africa, and explored the impact of HAART-related drug toxicities on quality of life.MethodsHealth-related quality of life was assessed using a standardised questionnaire, the Medical Outcomes Survey Short Form 36. Physical health summary scores and mental health summary scores were compared pre-HAART and at regular intervals during the first 48 weeks of HAART. The relationships between socio-demographic, baseline and on-treatment variables and decline in health-related quality of life, as well as the impact of drug toxicities on quality of life, were assessed in unadjusted bivariate and adjusted multivariate analyses.ResultsTwo hundred and ninety-five patients were enrolled into the study. There was a significant increase in health-related quality of life during the first 48 weeks on HAART. The median physical health summary score increased from 45 to 53 units (p < 0.001) and median mental health summary score increased from 45 to 50 units (p < 0.001).The bulk of this increase occurred during the first 16 weeks. Overall, 23% of participants experienced a decline in their physical health summary score, while 34% showed a decline in the mental health summary score. Average drops in median physical and mental health summary scores were 8.4 units (SD 9.31) and 9.9 (SD 11.4) units respectively. Participants with drug toxicity had lower physical health summary scores than participants without drug toxicity at all time points. However, only three participants with toxicity (27%) reported an actual decline in health-related quality of life by week 48. Drug toxicities had little impact on mental health summary scores.ConclusionThese results confirm the health-related quality of life benefits of HAART. While the majority of patients experienced a significant improvement in health-related quality of life on HAART, up to a third of patients reported declines in this quality of life. This was largely related to better baseline clinical state. HAART-related drug toxicities did not have a significant impact on health-related quality of life during the first year of HAART, which supports the ongoing use of the current national first-line regimen.

Impacto de la inmunodepresión basal y su grado de recuperación al año de terapia antirretroviral en sobrevida, complicaciones oportunistas y reacción de recuperación inmune

Baseline (BL) CD4 cell count is a major factor in outcome of highly active antiretroviral therapy (HAART); treatment induced immune recovery and viral response can modulate this outcome.To evaluate the association between baseline CD4 cell count and outcome during the first HAART regimen.Prospective study in 2,050 patients on first HAART with a follow up (f/u) ofat least 1 year. All had BL CD4 and viral load (VL) counts which were repeated at least twice a year. Patients were grouped according to BL CD4 (cells/mm(3)) in <100 (Gl), 100-199 (G2) and > or = (G3). Groups were further divided according to immune and virological response at 1 year in CD4 > or < 200 and VL detectable or undetectable (<80 copies/mL). Outcome measures were death, ALUS defining events (ADE) and, as a surrogate marker of immune recovery reaction, herpes zoster (HZ).During the first year of follow up, 113 patients (10.8%) died in Gl (n =1,044), 17 (2.5%) in G2 (n =675) (Gl-2 p <0.05) and 9 (2.7%) in G3 (n =331) (G2-3 p NS). One hundred twenty five of 919 (13.6%) patients alive at 1 year had ADE in Gl, 55/643 (8.5%) in G2 (p <0.05) and 20/320 (5.2%) in G3 (G2-3 p NS). ADEs with follow up CD4 >vs< 200 were: 25/274 (9.1%) vs 100/643 (15 7%) in Gl (p <0.005); 28/404 (6.9%) vs 27/235 (11.2%) in G2 (p NS) and 18/281 (6.4%) vs 2/41 (4.8%) in G3 respectively (p NS). Detectable VL was an additional risk for ADE only in Gl without CD4 recovery. HZ was seen in 6.6% of Gl vs 4% in G2 (p <0.05) and 4.3% in G3. HZ rate was higher in all groups reaching a follow up CD4 >200 than those who did not, with a statistically significant difference at p <0.05 only in Gl (9.5% vs 5.3%).The occurrence of death and ADE during the first year of HAART was significantly higher in patients with aBL CD4 <100, but no statistically significant difference was observed from BL CD4 >100 upwards. Immune recovery during f/u in the more immunosuppressed group greatly improved the outcome. The group with lowest BL CD4 and greater immune recovery showed the highest rate of immune recovery reaction.

Impact of baseline CD4 count, immune recovery and viral suppression at 7 year of first highly active antiretroviral therapy on survival, AIDS defining events and immune recovery reactions

Baseline (BL) CD4 cell count is a major factor in outcome of highly active antiretroviral therapy (HAART); treatment induced immune recovery and viral response can modulate this outcome. To evaluate the association between baseline CD4 cell count and outcome during the first HAART regimen. Prospective study in 2,050 patients on first HAART with a follow up (f/u) ofat least 1 year. All had BL CD4 and viral load (VL) counts which were repeated at least twice a year. Patients were grouped according to BL CD4 (cells/mm(3)) in <100 (Gl), 100-199 (G2) and > or = (G3). Groups were further divided according to immune and virological response at 1 year in CD4 > or < 200 and VL detectable or undetectable (<80 copies/mL). Outcome measures were death, ALUS defining events (ADE) and, as a surrogate marker of immune recovery reaction, herpes zoster (HZ). During the first year of follow up, 113 patients (10.8%) died in Gl (n =1,044), 17 (2.5%) in G2 (n =675) (Gl-2 p <0.05) and 9 (2.7%) in G3 (n =331) (G2-3 p NS). One hundred twenty five of 919 (13.6%) patients alive at 1 year had ADE in Gl, 55/643 (8.5%) in G2 (p <0.05) and 20/320 (5.2%) in G3 (G2-3 p NS). ADEs with follow up CD4 >vs< 200 were: 25/274 (9.1%) vs 100/643 (15 7%) in Gl (p <0.005); 28/404 (6.9%) vs 27/235 (11.2%) in G2 (p NS) and 18/281 (6.4%) vs 2/41 (4.8%) in G3 respectively (p NS). Detectable VL was an additional risk for ADE only in Gl without CD4 recovery. HZ was seen in 6.6% of Gl vs 4% in G2 (p <0.05) and 4.3% in G3. HZ rate was higher in all groups reaching a follow up CD4 >200 than those who did not, with a statistically significant difference at p <0.05 only in Gl (9.5% vs 5.3%). The occurrence of death and ADE during the first year of HAART was significantly higher in patients with aBL CD4 <100, but no statistically significant difference was observed from BL CD4 >100 upwards. Immune recovery during f/u in the more immunosuppressed group greatly improved the outcome. The group with lowest BL CD4 and greater immune recovery showed the highest rate of immune recovery reaction.

HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: a collaborative analysis

Highly active antiretroviral therapy (HAART) for the treatment of HIV infection was introduced a decade ago. We aimed to examine trends in the characteristics of patients starting HAART in Europe and North America, and their treatment response and short-term prognosis. We analysed data from 22,217 treatment-naive HIV-1-infected adults who had started HAART and were followed up in one of 12 cohort studies. The probability of reaching 500 or less HIV-1 RNA copies per mL by 6 months, and the change in CD4 cell counts, were analysed for patients starting HAART in 1995-96, 1997, 1998, 1999, 2000, 2001, and 2002-03. The primary endpoints were the hazard ratios for AIDS and for death from all causes in the first year of HAART, which were estimated using Cox regression. The proportion of heterosexually infected patients increased from 20% in 1995-96 to 47% in 2002-03, and the proportion of women from 16% to 32%. The median CD4 cell count when starting HAART increased from 170 cells per muL in 1995-96 to 269 cells per muL in 1998 but then decreased to around 200 cells per muL. In 1995-96, 58% achieved HIV-1 RNA of 500 copies per mL or less by 6 months compared with 83% in 2002-03. Compared with 1998, adjusted hazard ratios for AIDS were 1.07 (95% CI 0.84-1.36) in 1995-96 and 1.35 (1.06-1.71) in 2002-03. Corresponding figures for death were 0.87 (0.56-1.36) and 0.96 (0.61-1.51). Virological response after starting HAART improved over calendar years, but such improvement has not translated into a decrease in mortality.

Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries

Highly active antiretroviral therapy (HAART) is being scaled up in developing countries. We compared baseline characteristics and outcomes during the first year of HAART between HIV-1-infected patients in low-income and high-income settings. 18 HAART programmes in Africa, Asia, and South America (low-income settings) and 12 HIV cohort studies from Europe and North America (high-income settings) provided data for 4810 and 22,217, respectively, treatment-naïve adult patients starting HAART. All patients from high-income settings and 2725 (57%) patients from low-income settings were actively followed-up and included in survival analyses. Compared with high-income countries, patients starting HAART in low-income settings had lower CD4 cell counts (median 108 cells per muL vs 234 cells per muL), were more likely to be female (51%vs 25%), and more likely to start treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (70%vs 23%). At 6 months, the median number of CD4 cells gained (106 cells per muL vs 103 cells per muL) and the percentage of patients reaching HIV-1 RNA levels lower than 500 copies/mL (76%vs 77%) were similar. Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20,532 person-years). The adjusted hazard ratio (HR) of mortality comparing low-income with high-income settings fell from 4.3 (95% CI 1.6-11.8) during the first month to 1.5 (0.7-3.0) during months 7-12. The provision of treatment free of charge in low-income settings was associated with lower mortality (adjusted HR 0.23; 95% CI 0.08-0.61). Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries. Timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART, might reduce this excess mortality.

Occult Hepatitis B Virus Infection before and 1 Year after Start of HAART in HIV Type 1-Positive Patients

Occult hepatitis B virus (HBV) infection is diagnosed when HBc antibodies and HBV-DNA are detectable in serum while hepatitis B surface antigen (HBsAg) is not. The clinical relevance of this phenomenon in HIV-1 patients starting highly active antiretroviral therapy (HAART) is unknown. We followed 93 therapy naive HIV-1-infected adults who were anti-HBc positive, HBsAg and HBeAg negative, during first year of HAART. At baseline, HBV-DNA was quantified, and HBV genotype was determined in the HBV-DNA-positive patients by sequencing a part of the HBV genome. Four of 93 patients (4%) were HBV DNA positive at baseline. All four patients tested negative for HBV-DNA after 1 year. They all received lamivudine as part of their HAART. They had no clinically significant liver enzyme elevations (LEE) during the first year of HAART. Two of the patients had a genotype A, one genotype E, and in the fourth patient sequencing was not possible. In one patient we found significant mutations in the a determinant region of HBsAg, at positions 142 and 144. In our population of therapy-naive HIV-1-infected adults who were anti-HBc positive, we found occult HBV infection in 4% of the patients. We did not find an increased risk for LEE in our population of patients after the start of HAART. Our results illustrate that occult HBV infection is more a diagnostic than a clinical problem. It may be caused by very low levels of HBV replication, concurrent presence of HBsAg and anti-HBs, or mutations in the HBsAg a determinant.

Effect of Treatment, during Primary Infection, on Establishment and Clearance of Cellular Reservoirs of HIV-1

Patients in whom virologic suppression is achieved with highly active antiretroviral therapy (HAART) retain long-lived cellular reservoirs of human immunodeficiency virus type 1 (HIV-1); this retention is an obstacle to sustained control of infection. To assess the impact that initiating treatment during primary HIV-1 infection has on this cell population, we analyzed the decay kinetics of HIV-1 DNA and of infectivity associated with cells activated ex vivo in 27 patients who initiated therapy before or <6 months after seroconversion and in whom viremia was suppressed to <50 copies/mL. The clearance rates of cellular reservoirs could not be distinguished by these techniques (median half-life, 20 weeks) during the first year of HAART. The clearance of HIV-1 DNA slowed significantly during the subsequent 3 years of treatment (median half-life, 70 weeks), consistent with heterogeneous cellular reservoirs being present. Total cell-associated infectivity (CAI) after 1 year of treatment was undetectable (<0.07 infectious units/million cells [IUPM]) in most patients initiating treatment during primary infection either before (9/9) or <6 months after (6/8) seroconversion. In contrast, all 17 control patients who initiated HAART during chronic infection retained detectable CAI after 3-6 years of treatment (median reservoir size, 1.1 IUPM; P<.0005). These results suggest that treatment <6 months after seroconversion may facilitate long-term control of cellular reservoirs that maintain HIV-1 infection during treatment.