Highly Active Antiretroviral Treatment Initiation Research Articles

Leprosy as immune reconstitution inflammatory syndrome in patients living with HIV: Description of French Guiana's cases over 20 years and systematic review of the literature.

HIV infection is highly prevalent in French Guiana, a territory where leprosy is also endemic. Since the introduction of Highly Active Antiretroviral Treatment (HAART) in the management of HIV, leprosy has been reported as part of the immune reconstitution inflammatory syndrome (IRIS). We aimed to present a general description of these forms of leprosy as IRIS, highlighting clinical and therapeutic specificities. A retrospective study was conducted in French Guiana, including patients living with HIV (PLHIV) with advanced infection (CD4 < 200/mm3) and developing leprosy or a leprosy reaction within six months of HAART initiation, from 2000 to 2020. Clinical, histological and biological data were collected for all these patients. Six patients were reported in French Guiana. A systematic review of the literature was conducted, and its results were added to an overall analysis. Overall, seventy-three PLHIV were included. They were mainly men (74%), aged 22-54 years (median 36 years), mainly from Brazil (46.5%) and India (32.8%). Most leprosy cases (56.2%) were borderline tuberculoid (BT). Leprosy reactions were frequent (74%), mainly type 1 reaction (T1R) (68.5%), sometimes intense with ulceration of skin lesions (22%). Neuritis was observed in 30.1% of patients. The outcome was always favorable under multidrug therapy (MDT), continuation of HAART and additional corticosteroid therapy in case of neuritis or ulceration. There was no relapse. Leprosy as IRIS in PLHIV mainly presents as a BT leprosy in a T1R state, sometimes with ulcerated skin lesions. Response to MDT is usually good. Systemic corticosteroids are necessary and efficient in case of neuritis.

Hematological Abnormalities of Adult HIV-Infected Patients Before and After Initiation of Highly Active Antiretroviral Treatment at Debre Tabor Comprehensive Specialized Hospital, Northcentral Ethiopia: A Cross-Sectional Study.

BackgroundHematological abnormalities have been associated with an increased risk of disease progression and death in people living with human immunodeficiency virus (HIV). The use of antiretroviral medications can have a positive or negative effect on the hematological disorder. However, little is known about its impact on hematological parameters in antiretroviral-treated patients in Ethiopia, especially in the study area.MethodsA cross-sectional study was conducted at Debre Tabor Comprehensive Specialized Hospital from September to November 2020. A total of 334 HIV-infected patients taking highly active antiretroviral treatment (HAART) at least for 6 months were selected using a simple random sampling technique. Socio-demographic and clinical characteristics of the study subjects were collected using a semi-structured questionnaire. Hematological and immunological parameters were determined using Sysmex kx-21 hematology analyzer and BD FACS count CD4 analyzer, respectively. Statistical analysis was done using SPSS version 20 statistical software. A P-value <0.05 was considered statistically significant.ResultsA total of 334 HIV patients were included in this study. The prevalence of anemia, leucopenia, neutropenia, lymphopenia and thrombocytopenia were 37.1%, 22.8%, 8.4%, 10.5% and 17.1% before initiation of HAART and 17.4%, 34.2%, 18.8%, 13.1% and 8.3% after initiation of HAART, respectively. There was a significant difference in total white blood cell (WBC) count, absolute neutrophil count (ANC), red blood cell (RBC) count, hemoglobin value, mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet and CD4+ T cell counts in HIV patients before and after initiation of HAART (P<0.05).ConclusionThe most common hematological abnormalities observed in this study before and after HAART initiation were anemia, leucopenia, neutropenia, lymphopenia, and thrombocytopenia. However, after beginning HAART, the prevalence of anemia and thrombocytopenia decreased dramatically.

Echocardiographic abnormalities in children and adolescents living with human immunodeficiency virus on highly active antiretroviral treatment.

The availability and use of highly active antiretroviral treatment (HAART) has turned human immunodeficiency virus (HIV) into a chronic disease, allowing patients to live much longer. To report asymptomatic cardiac abnormalities in children and adolescents based on both conventional and tissue Doppler imaging (TDI) echocardiography. One hundred and fifty-one patients on HAART were recruited. Demographic and clinical variables were collected through patient interviews and medical record reviews. Conventional echocardiography and TDI were performed on each patient. Mean age was 13.0 ± 3.2 (4.0-19.0) years. Eightythree patients (55%) were female. Age at diagnosis of HIV infection was 5.7 ± 3.3 years. Age at initiation of HAART was 7.34 ± 3.54 years, while duration of HAART was 59 ± 39.1 months. On conventional echocardiography, three cases of left ventricular (LV) systolic dysfunction, two of pulmonary hypertension and one of minimal pericardial effusion were identified. Calculation of myocardial mass index (MMI) revealed that 16 patients had abnormal values. Twenty-seven (17.9%) patients had evidence of LV diastolic dysfunction and 18 (11.9%) had right ventricular (RV) diastolic dysfunction. Nineteen (12.6%) patients had tricuspid annular systolic velocity of < 9.5 cm/s, indicating asymptomatic RV systolic dysfunction. While few patients had abnormalities such as reduced LV ejection fraction, pulmonary hypertension and minimal pericardial effusion detectable on conventional echocardiography, a larger proportion of patients had subtle abnormalities such as increased MMI, LV diastolic dysfunction on TDI, RV dysfunction and abnormal myocardial performance index. Such patients may need routine screening and cardiac follow up.

Morbidity and mortality in HIV-infected children on antiretroviral therapy in Togo.

the aim of this study was to evaluate the mortality and morbidity of HIV-infected children on highly active antiretroviral treatment (HAART) in Togo. this is a retrospective study of HIV-infected children on HAART in the 25 largest centers of HIV/AIDS care in Togo. the study included 1861 children (sex-ratio=0.99). Among them, 35.6% were in WHO clinical stages 3 or 4 at the beginning of HAART. The most common opportunistic infections were coughing and pneumonia (37.1%), gastroenteritis (11.3%), various bacterial infections (10.4%), and pruritus (10.4%). The incidence of death was estimated at 4.5 per 100 person-years. Mortality was highest during the first year of antiretroviral therapy. The survival rate at 12 months of ART was 92.6%. Children who began HAART at WHO clinical stage 4 had a significantly lower survival rate than the others (P<0.0001). The presence of a side effect of HAART (P=0.041), and hospitalization (P<0.001) were significantly associated with death in these children. although the new recommendations for medical care require early initiation of HAART, the improved performance of programs to prevent maternal-infant transmission remains crucial in reducing morbidity and mortality of children on HAART in Togo.

Maternal and obstetric complications among HIV-infected women treated with highly active antiretroviral treatment at a Regional Hospital in Durban, South Africa.

HIV is the leading cause of maternal deaths in resource-poor countries. The use of highly active antiretroviral treatment (HAART) has been shown to almost eliminate vertical transmission and improve maternal health outcomes. Its effect on direct obstetric conditions has not been well documented. We conducted a retrospective study of women who delivered at a regional hospital from April 1, 2011, to April 30, 2014. We employed a stratified random selection, where the first 50 files recorded in the birth register during each calendar month were chosen, at a ratio of one HIV uninfected for every 4 infected women. We analyzed files belonging to 302 HIV-uninfected women and 1159 HIV-infected women. The latter were further subdivided into those who used zidovudine, n = 424; those who initiated HAART prepregnancy, n = 312; and those who initiated in-pregnancy HAART, n = 423. We found that despite the use of HAART, HIV-infected women were at increased risk of both respiratory and lower genital tract infections (P = 0.009 and 0.001 respectively), compared to HIV-uninfected women. The women receiving HAART before pregnancy had an increased risk of preterm births (P = 0.004), and poor perinatal outcomes (P = 0.002); however, postpartum complications were reduced (P = 0.023). There was a trend toward an increased risk of preeclampsia (P = 0.064). The initiation of HAART before pregnancy reduces the frequency of postpartum complications. However, compared to HIV-negative women, women receiving HAART prepregnancy remained at risk of infectious morbidity, had poor perinatal outcomes, and may also be at an increased risk of preeclampsia.

Survival Pattern and Its Determinants among Adult HIV-Infected Patients after Initiation of HAART in Dilla Hospital Ethiopia

Background: In resource poor countries like Ethiopia the survival of patients treated with ART depends on a variety of factors, which might vary greatly with economic, demographic, behavioral and health risk factors. However, factors affecting survival in Ethiopia are poorly understood. The aim of this study is to determine causes of mortality in adult HIVpositive patients receiving highly active anti-retroviral treatment (HAART) in Dilla referral Hospital. Methods: The medical records of 1391 ART patients who enrolled at Dilla Hospital between 2010 and 2014 were reviewed and sociodemographic, clinical, behavioral and immunological data were collected. Multivariable Cox proportional hazards regression model was used to measure risk of death and identify the independent predictors of mortality. Result: Out of 1391 cohorts of adults ART patients 1081 (77.7%) were alive and continued their treatment in the hospital, 128 (9.2%) were reported dead, 111 (8%) were transfer out, and 71 (5.1%) were lost follow up. The probability of remaining alive and on treatment after 60 months of follow up was 89.3% for TB/HIV patients and 91.1% for HIV only infected patients. HIV patients who developed TB had shorter survival time than not developed TB. Death occurred 26% and 52% in the first 3 and 12 months of ART initiation respectively. The overall incidence rate of mortality during ART treatment was 3.5 per 100 person year observations (PYO). In multivariate analysis low body weight BMI &lt;18.5 kg/m2 (HR 3.12, 95% CI 1.39-7.76, P&lt;0.0001), CD4 countless than 50 cells/mm3 (HR 4.55, 95% CI 1.19 – 8.44, p &lt;0.002), anemia, WHO clinical stage III and IV, drug addiction and presence of active TB infection were predictor of survival and statistically significant association with mortality in HIV patients under ART follow up. Conclusion: The presence of lower baseline CD4-cell, TB infection, WHO clinical stage III and IV, lower body weight, anemia, and drug addiction were factors associated with mortality among ART clients. Improving nutritional status, prevention and control of TB and other opportunistic infections were the recalled recommendations to decrease AIDSrelated morality. These determinants should be taken into account by health care providers to enhance better clinical outcomes of ART attendees.

Predictors of suboptimal CD4 response among women achieving virologic suppression in a randomized antiretroviral treatment trial, Africa.

BackgroundA subset of HIV-1 infected patients starting highly active antiretroviral treatment (HAART) experience suboptimal CD4 response (SCR) despite virologic suppression. We studied the rate of and risk factors for SCR among women starting HAART in the ACTG A5208 study conducted in 7 African countries. 741 HAART-naive women with screening CD4 count <200 cells/μL were randomized to start HAART with Tenofovir/Emtricitabine plus either Nevirapine or Lopinavir/Ritonavir.MethodsThis analysis includes the 625 women who remained on-study through 48 weeks without experiencing protocol-defined virologic failure. We defined SCR as < 100 CD4 cells/μL increase from baseline and absolute CD4 cell count < 350 cells/μL, both at 48 weeks after HAART initiation.ResultsThe baseline characteristics for the 625 women prior to HAART initiation were: median age 33 years, screening CD4 count 134 cells/μL, and HIV-1 RNA 5.1 log10 copies/mL; 184 (29%) were WHO Stage 3 or 4.Seventy one (11%) of these 625 women experienced SCR. Baseline factors independently associated with increased odds of SCR included older age, lower HIV-1 RNA, positive Hepatitis B surface antigen, and site location. At 96 weeks, only 6% of the SCR group had CD4 ≥ 350 cells/μL compared with 67% in the non SCR group.ConclusionAfter starting HAART, 11% of women with virologic suppression through 48 weeks experienced SCR. These patients were also less likely to achieve CD4 ≥ 350 cells/μL by 96 weeks. The underlying causes and long term clinical implications of SCR deserve further investigation.Trial registrationClinicaltrials.gov Identifier: NCT00089505

Dynamic changes of cellular HIV-1 DNA quantification during highly active antiretroviral therapy in Chinese HIV infected individuals

To observe the dynamic changes of 3 types of viral reservoir cells (NK cells, T lymphocytes and monocytes), and its relationship with treatment effect in Chinese HIV-1 infected patients receiving highly active antiretroviral treatment (HAART) for 2 years. A total of 40 chronic HIV-1-infected adults who initiated HAART were enrolled in this study and followed up for 2 years. Peripheral whole blood was obtained from each patient at baseline (0 month), 6, 12, 18 and 24 months. Real-time fluorescent quantitative PCR was used to detect the HIV-1 RNA in the plasma and HIV-1 DNA in NK cells, T lymphocytes and monocytes. All the data were statistically analyzed. CD4 count increased with the decrease of the viral load during HAART. After HAART initiation, HIV-1 DNA showed a significant decrease in NK cells, T lymphocytes and monocytes. The HIV-1 DNA from T lymphocytes, NK cells and monocytes correlated positively with the HIV- 1 RNA (P<0.05) while NK cells and T lymphocytes correlated negatively with CD4+ T cell count. However we did not find significant correlation between CD4+ T cell count and HIV-1 DNA in monocytes at the baseline of HAART. This study found that NK cell was an important HIV cellular reservoir besides T lymphocytes and monocytes. T lymphocytes may be the main long lasting HIV reservoir. HIV-1 proviral DNA may play an important role in the efficacy of treatment and monitoring the disease progression.

Adherence to and Effectiveness of Highly Active Antiretroviral Treatment for HIV Infection

It is well established that high adherence to HIV-infected patients on highly active antiretroviral treatment (HAART) is a major determinant of virological and immunologic success. Furthermore, psychosocial research has identified a wide range of adherence factors including patients' subjective beliefs about the effectiveness of HAART. Current statistical approaches, mainly based on the separate identification either of factors associated with treatment effectiveness or of those associated with adherence, fail to properly explore the true relationship between adherence and treatment effectiveness. Adherence behavior may be influenced not only by perceived benefits-which are usually the focus of related studies-but also by objective treatment benefits reflected in biological outcomes. Our objective was to assess the bidirectional relationship between adherence and response to treatment among patients enrolled in the ANRS CO8 APROCO-COPILOTE study. We compared a conventional statistical approach based on the separate estimations of an adherence and an effectiveness equation to an econometric approach using a 2-equation simultaneous system based on the same 2 equations. Our results highlight a reciprocal relationship between adherence and treatment effectiveness. After controlling for endogeneity, adherence was positively associated with treatment effectiveness. Furthermore, CD4 count gain after baseline was found to have a positive significant effect on adherence at each observation period. This immunologic parameter was not significant when the adherence equation was estimated separately. In the 2-equation model, the covariances between disturbances of both equations were found to be significant, thus confirming the statistical appropriacy of studying adherence and treatment effectiveness jointly. Our results, which suggest that positive biological results arising as a result of high adherence levels, in turn reinforce continued adherence and strengthen the argument that patients who do not experience rapid improvement in their immunologic and clinical statuses after HAART initiation should be prioritized when developing adherence support interventions. Furthermore, they invalidate the hypothesis that HAART leads to "false reassurance" among HIV-infected patients.

Incidence of tuberculosis and early mortality in a large cohort of HIV infected patients receiving antiretroviral therapy in a tertiary hospital in Addis Ababa, Ethiopia

Preceding studies on morbidities and mortalities associated with TB in a cohort of HIV care indicate high incidence of TB development and premature death among patients on highly active antiretroviral treatment (HAART). This study aims to measure the rate of TB, TB mortality, and associated risk factors following commencement of HAART in a cohort of patients attending HIV care in Ethiopia. Patient information was gathered from the hospital register and analysed. TB incidence peaked within six months of HAART initiation, and dropped from 3.3/100 person-years in the first year to 0.4/100 person-years in the fifth year. At baseline, risk factors associated with TB included WHO clinical stage 3 HIV infection (adjusted hazard ratio (AHR) 2.53; 95% CI 1.70-3.70), WHO clinical stage 4 HIV infection (AHR, 3.86; 95% CI 2.54-5.86), and patients who were bed ridden >50% a day (AHR, 1.52; 95% CI 1.13-2.05). The rate of mortality was 6.9% (incidence 2.8 per 100 person-years) and 57% of deaths occurred in the first six months of HAART initiation. Multivariate Cox model indicated WHO clinical stage 4 HIV infection, CD4+ cell count <50 cells/μl, bed ridden >50% a day, and TB after HAART initiation as baseline independent predictors of mortality. Additional evidence shows that regular CD4+monitoring of patients before HAART initiation as well as earlier HAART initiation decreases death, and regular clinical staging decreases TB incidence.

Retention in a public healthcare system with free access to treatment

We aimed to assess retention of HIV-infected individuals in the Danish healthcare system over a 15-year period. Loss to follow-up (LTFU) was defined as 365 days without contact to the HIV care system. Data were obtained from the nationwide Danish HIV Cohort study, The Danish National Hospital Registry and The Danish Civil Registration System. Incidence rates, risk factors for LTFU and return to care and mortality rate ratios (MRRs) were estimated using Poisson regression analyses. We included 4745 HIV patients who were followed for 36,692 person-years. Patients were retained in care 95.0% of person-years under observation, increasing to 98.1% after initiation of highly active antiretroviral treatment (HAART). The overall incidence rate/100 person-years for first episode of LTFU was 2.6 [95% confidence interval (CI) 2.5-2.8] and was significantly lower after initiation of HAART [1.2 (95% CI 1.0-1.3)]. Five years after LTFU the probability of return to care was 0.87 (95% CI 0.84-0.90). The risk of death was significantly increased after LTFU [MRR 1.9 (95% CI 1.6-2.6)] and 6 months or less after return to care [MRR 10.9 (95% CI 5.9-19.9)]. Retention in care of Danish HIV patients is high, especially after initiation of HAART. Absence from HIV care is associated with increased mortality. We conclude that high rates of retention can be achieved in a healthcare system with free access to treatment and is associated with a favorable outcome.

Using quality improvement to accelerate highly active antiretroviral treatment coverage in South Africa

IntroductionThe authors report on a health systems strengthening intervention using quality improvement (QI) methods at the subdistrict level to accelerate highly active antiretroviral treatment (HAART) initiation in South Africa.MethodsUsing a...

Risk factors for tuberculosis after highly active antiretroviral treatment (HAART) initiation among HIV patients: A systematic review

Background Tuberculosis is one of the most frequent causes of death among adults despite being nearly 100% curable in the developing world. The lifetime risk of tuberculosis in immune competent persons is 5% to 10%, but in HIV positive individuals, there is a 5% to 15% annual risk of developing active tuberculosis disease and there appears to be little research addressing HIV and tuberculosis co-infection. Objective To synthesise the best available evidence on risk factors for developing tuberculosis after highly active antiretroviral treatment initiation among HIV patients Inclusion criteria Types of participants HIV patients who had initiated highly active antiretroviral treatment and were above 15 years of age. Phenomena of interest Risk factors for developing active tuberculosis among HIV patients after initiation of highly active antiretroviral treatment. Types of studies Analytical epidemiological study designs were included in the review. Types of outcomes The studies considered in this review included socio-demographic and clinical variables as risk factors for developing tuberculosis after HAART initiation such as, but not limited to: baseline CD4 count, HAART type, WHO clinical stage of HIV, previous history of TB and gender14, 15. Search Strategy English language articles published between January 1997 and December 2011 were searched using a comprehensive search strategy. Assessment of methodological quality Conducted, using the Joanna Briggs Institute critical appraisal tools. Data extraction Carried out, using the Joanna Briggs Institute data extraction tool. Data synthesis Meta- analysis was conducted using random effects model with Rev Man 5 software. Results Five cohort studies were included in the review. The risk of developing active tuberculosis after initiating highly active antiretroviral treatment was found to be 2.14 times higher in subjects with a baseline CD4+ cell count ≥ 200 than their counterparts with a 95% CI from 1.52 to 3.02 and this effect was statistically significant, p<0.0001. The overall effect of gender on development of post highly active antiretroviral treatment tuberculosis was found to be not significant, p=0.64. The meta analysis for prior TB history as a risk factor favoured those who didn't have prior tuberculosis history to have 1.24 times higher risk than their counter parts even if it is not found to be statistically significant, p=0.56. There was no difference identified in the risk of developing post highly active antiretroviral treatment tuberculosis among patients taking protease inhibitor based treatment regimens and those taking non nucleoside reverse transcriptase inhibitor based treatment regimen. The last variable considered as a risk factor for post highly active antiretroviral treatment tuberculosis was the WHO's clinical stages for HIV and the risk was found to be 1.77 times higher among those who were at stage 1 or 2 during enrolment than their counterparts but this risk is not statistically significant, p=0.44. Conclusions Having no prior tuberculosis history, female gender and WHO clinical stage of HIV at enrolment were found to be a risk but their relation with post highly active antiretroviral treatment tuberculosis was not statistically significant. The meta-analysis also did not identify any difference among the groups taking protease inhibiter based and non nucleoside reverse transcriptase inhibiters (NNRTI) based treatments in relation to post highly active antiretroviral treatment tuberculosis. But, the analysis revealed that there exists a statistically significant risk for developing post highly active antiretroviral treatment tuberculosis among individuals having a baseline CD4+ cell count ≥ 200 being found to be at higher risk.

The Impact of Highly Active Antiretroviral Treatment on the Blood Profiles of Patients with Acquired Immune Deficiency Syndrome

This study retrospectively investigated the short- and long-term impact of highly active antiretroviral treatment (HAART) on the blood profiles of patients with acquired immune deficiency syndrome (AIDS), and their relationship with disease progression. CD4(+) T-cell count was measured by flow cytometry, plasma viral load of human immunodeficiency virus (HIV) RNA was detected by reverse transcription-polymerase chain reaction, and blood profile was determined by an automated analyser. CD4(+) T-cell count, total lymphocyte count (TLC) and haemoglobin concentration improved gradually in patients with AIDS after the initiation of HAART. Long-term effective HAART significantly increased CD4(+) T-cell counts TLC and haemoglobin concentrations, and reduced viral load to undetectable levels. An increase in haemoglobin was positively correlated with an increase in CD4(+) T-cells. These findings suggest that TLC is a valuable tool for determining the initiation of HAART, and that the haemoglobin concentration could be an additional indicator for long-term monitoring of HAART in resource-limited settings.

Late Initiation of HAART Among HIV-Infected Patients in Spain Is Frequent and Related to a Higher Rate of Virological Failure but not to Immigrant Status

Purpose: To determine whether immigrant status is associated with late initiation of highly active antiretroviral treatment (HAART) and/or poor response to antiretrovirals. Methods: GESIDA 5808 is a multicenter, retrospective cohort study (inclusion period January 2005 through December 2006) of treatment-naïve patients initiating HAART that compares HIV-infected patients who are immigrants with Spanish-born patients. A late starter (LS) was defined as any patient starting HAART with a CD4+ lymphocyte count <200 cells/μL and/or diagnosis of an AIDS-defining illness before or at the start of therapy. The primary endpoint was time to treatment failure (TTF), defined as virological failure (VF), death, opportunistic infection, treatment discontinuation/switch (D/S), or missing patient. Secondary endpoints were time to treatment failure as observed data (TTO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/S not due to VF). Results: LS accounted for 56% of the patients. Lower educational and socioeconomic level and intravenous drug use (IVDU) were associated with categorization as LS, but immigrant status was not. Cox regression analysis (hazard ratio [HR]; 95% CI) between LS and non-LS patients showed no differences in TTF (0.97; 0.78–1.20) or TTO (1.18; 0.88–1.58), although it did reveal a difference in TVF (1.97; 1.18–3.29). CD4+ lymphocyte recovery was equivalent for both LS and non-LS patients (159 vs 173). Conclusions: In our cohort, immigrant status was not shown to be related to late initiation of HAART. Although LS patients did not have a longer TTF for any reason, TVF was significantly shorter. Despite universal free access to HAART in Spain, measures to ensure early diagnosis and treatment of HIV infection are necessary.

Treatment and disease progression in a birth cohort of vertically HIV-1 infected children in Ukraine

BackgroundUkraine has the highest HIV prevalence (1.6%) and is facing the fastest growing epidemic in Europe. Our objective was to describe the clinical, immunological and virological characteristics, treatment and response in vertically HIV-infected children living in Ukraine and followed from birth.MethodsThe European Collaborative Study (ECS) is an ongoing cohort study, in which HIV-1 infected pregnant women are enrolled and followed in pregnancy, and their children prospectively followed from birth. ECS enrolment in Ukraine started in 2000 initially with three sites, increasing to seven sites by 2009.ResultsA total of 245 infected children were included in the cohort by April 2009, with a median age of 23 months at most recent follow-up; 33% (n = 77) had injecting drug using mothers and 85% (n = 209) were infected despite some use of antiretroviral prophylaxis for prevention of mother-to-child transmission. Fifty-five (22%) children had developed AIDS, at a median age of 10 months (IQR = 6-19). The most prevalent AIDS indicator disease was Pneumocystis jiroveci pneumonia (PCP). Twenty-seven (11%) children had died (median age, 6.2 months). Overall, 108 (44%) children had started highly active antiretroviral treatment (HAART), at a median 18 months of age; median HAART duration was 6.6 months to date. No child discontinued HAART and 92% (100/108) remained on their first-line HAART regimen to date. Among children with moderate/severe immunosuppression, 36% had not yet started HAART. Among children on HAART, 71% (69/97) had no evidence of immunosuppression at their most recent visit; the median reduction in HIV RNA was 4.69 log10 copies/mL over a median of 10 months treatment. From survival analysis, an estimated 94%, 84% and 81% of children will be alive and AIDS-free at 6, 12 and 18 months of age, respectively. However, survival increased significantly over time: estimated survival rates to 12 months of age were 87% for children born in 2000/03 versus 96% for those born in 2004/08.ConclusionOne in five children had AIDS and one in ten had died. The half of children who received HAART has responded well and survival has significantly improved over time. Earlier diagnosis and prompt initiation of HAART remain key challenges.

Achieving the National Strategic Plan: A practical calculator for local target setting in district health facilities

The South African HIV National Strategic Plan (NSP) aims to provide access to appropriate treatment, care and support to 80% of the HIV-infected population by 2011. By mid-2008, highly active antiretroviral treatment (HAART) was being dispensed to about half the HIV-infected population in need. Reaching the NSP targets will require full mobilisation of all of South Africa's health facilities. While the NSP has broad political and programmatic support from the Department of Health and civil society, and managers are able to recite the national targets, it has been difficult for these managers to relate the targets to their own geographical areas of responsibility. National, regional and district targets for HIV care have been set from South Africa's relatively good census, modelling and epidemiological data. However, few practical tools are available to help clinicians and managers understand their facility's actual contribution to the district regional and national NSP targets for each step of the HIV care pathway (HIV testing, CD4 testing, HAART referral and initiation). The calculation of HAART initiation targets is complicated by the anticipated additional demand for treatment that will be generated by a change in the recommended CD4-count threshold for initiation of treatment.4 Accordingly, we provide a data-based tool that is readily available, and that district and facility managers can use to calculate their annual steady-state HIV testing, CD4 testing and HAART initiation requirements. These calculated values can be used for local and regional planning and to assess and improve current performance at facility level.

Antiretroviral Treatment Initiation Among HIV-Infected Pregnant Women with Low CD4+ Cell Counts in Gaborone, Botswana

Botswana has the most comprehensive public program in Africa for providing antiretroviral therapy to treat HIV and prevent mother-to-child transmission (PMTCT). Botswana guidelines prioritize CD4(+) cell count testing during pregnancy and initiation of highly active antiretroviral treatment (HAART) for women who qualify for treatment. We analyzed rates of HIV testing, CD4 cell count testing, and HAART initiation during pregnancy. From October 2007 through June 2008, we reviewed obstetric and laboratory records of women at Princess Marina Hospital in Gaborone, Botswana. We recorded information from 3056 women. Of 2675 women eligible for the PMTCT program, 2623 (98%) had a documented HIV status, of whom 793 (30%) were HIV infected. Among women who were treatment naive at pregnancy conception, 397 (59%) had recorded CD4(+) cell counts, of whom 62 (16%) had a CD4(+) cell count <200 cells per cubic millimeter. Among this subset, 23 (37%) initiated HAART during pregnancy, 26 (42%) received zidovudine prophylaxis, and 13 (21%) received no therapy. We observed low rates of CD4(+) cell count testing and HAART initiation during pregnancy. Antenatal clinics should prioritize CD4(+) cell count testing and referral of women who qualify for HAART to maximize benefits of maternal treatment and PMTCT.

Changes in Cognition During Antiretroviral Therapy: Comparison of 2 Different Ranking Systems to Measure Antiretroviral Drug Efficacy on HIV-Associated Neurocognitive Disorders

Although HIV-associated neurocognitive disorders should be treated with highly active antiretroviral treatment (HAART) regimens with good central nervous system (CNS) penetration, the definition of neuroactive HAART remains controversial. We compared 2 ranking systems to measure HAART neuroeffectiveness. Patients with (n = 93) or at risk for (n = 92) HIV-associated neurocognitive disorders underwent neuropsychological (NP) test batteries before HAART initiation and at follow-up. Changes in normatively adjusted summary NP test z scores were calculated for each subject. Two neuropenetration scores were calculated: the central nervous system penetration reference score (number of drugs in the combination among zidovudine, abacavir, stavudine, lamivudine, efavirenz, nevirapine, indinavir, and lopinavir-ritonavir) and the CNS penetration-effectiveness (CPE) score: a summary score of 1 (high: penetration: [corrected] zidovudine, abacavir, delavirdine, [corrected] nevirapine, amprenavir-ritonavir, fosamprenavir-ritonavir, [corrected] indinavir-ritonavir, and lopinavir-ritonavir), 0.5 (intermediate penetration: [corrected] stavudine, lamivudine, emtricitabine, efavirenz, amprenavir, fosamprenavir, [corrected] atazanavir-ritonavir, atazanavir, [corrected] and indinavir), and 0 (low penetration: remaining ARVs) [corrected] for each drug in the combination. Main outcome measures were changes in global NPZ scores and in summary z scores on 5 domains. At regression analyses, higher CPE scores correlated with greater improvements in NPZ-4 (P = 0.0283), NPZ-8 (P = 0.0071), concentration and speed of mental processing (P = 0.0046), and mental flexibility (P = 0.0262) summary z scores. The correlation was stronger among NP-impaired patients. By contrast, higher estimates of neuroeffectiveness with the alternative system showed no correlation. No association was seen between CD4 and plasma viral load changes with both scores. The CPE score represents a step forward toward the identification of a clinically useful approach to estimating HAART ability to improve cognition.

Tenosynovitis as a possible feature of immune reconstitution syndrome during highly active antiretroviral treatment (HAART)

An immune reconstitution syndrome (IRS) occurs in between 10% and 25% of patients starting highly active antiretroviral treatment (HAART). A 49-year-old patient presents a tenosynovitis 6 weeks after HAART initiation. In our patient, exhaustive tests for infectious, inflammatory and drug-related causes of tenosynovitis were negative. The improvement obtained with high-dose Non-steroidal anti-inflammatory-drug (NSAID) therapy and the patient's immunovirologic profile, supported a diagnosis of tenosynovitis associated with immune reconstitution, a form of IRS that has not previously been described. This original case increase the broad spectrum of inflammatory rheumatologic disorders associated with HIV infection.