Efavirenz in pregnancy

Clinical guidelines from the National Department of Health (DoH), South Africa, for prevention of mother-tochild transmission (PMTCT), revised in 2010, recommend that HIV-positive pregnant women with a CD4 count of 350 cells/μl or less commence lifelong antiretroviral therapy (ART).¹ DoH guidance for women initiating ART in pregnancy in the public sector – on which the overwhelming majority of HIV-positive South Africans rely for their care – recommends they receive nevirapine with tenofovir and lamivudine or emtricitabine at any stage of gestation. In cases where a woman is already receiving ART with an efavirenz-based regimen, it is recommended that this should be substituted for nevirapine if she is still in the first trimester of pregnancy. Efavirenz is therefore contraindicated in pregnant women at any time during pregnancy; for those already receiving the drug, it is only switched in the first trimester. The concern about the use of efavirenz in pregnancy dates back to preclinical studies. It is the only antiretroviral with preclinical primate data and in turn has the strongest US Food and Drug Administration (FDA) category and the most scrutiny during pregnancy.² The drug also has the most conflicting recommendations, both from guidelines and product labelling. This article is a summary of what we know (and do not know) about using efavirenz in pregnancy. We argue that reconsideration of the risk and benefits of this evidence, which has informed South African guidance, is warranted

Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.

In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia

Evaluation of a diagnostic algorithm for smear-negative pulmonary tuberculosis in HIV-infected adults

Objective: To evaluate the diagnostic accuracy of and reduction in diagnostic delay attributable to a clinical algorithm used for the diagnosis of smear-negative pulmonarytuberculosi& (SNPTB) in HfV-infected adults.Design. An algorithm was designed to facilitate clinicoradiological diagnosis of pulmonary TB (PTB) in HIV-infected smear-negative adult patients. A folder review was performed on the first 58 cases referred for empirical TB treatment using this algorithm.Setting. Nolungile HIV Clinic, Site Khayelitsha.Subjects. Subjects included 58 HIV-infected adult patients with suspected PTB consecutively referred to the local TB clinic for outpatient TB treatment using this algorithm between 12 February 2004 and 30 April 2005.Outcome measures. Outcome measures were response of C-reactive protein, haemoglobin, weight and symptoms to TB treatment, and TB culture result. Diagnostic delay On days) was calculated.Results. Thirty-two of the 58 patients (55%) had positive TB cultures (definite TB). Initiation of TB treatment occurred on average 19.5 days before the positive culture report. A further 21 patients (36%) demonstrated clinical improvement on empirical treatment (probable/possible TB). Two did not improve and subsequently died without a definitive diagnosis. Three patients defaulted treatment.Conclusions.SNPTB is more common in HIV-infected patients and leads to diagnostic delay. This algorithm allowed for earlier initiation of TB treatment in HIV-infected patients presenting with symptoms of PTB and negative smears or nonproductive cough in a high TB incidence setting

Clinician compliance with laboratory monitoring and prescribing guidelines in HIV 1-infected patients receiving tenofovir

Background. Tenofovir is part of the preferred first-line regimen for HIV-infected patients in South Africa (SA), but is associated with kidney toxicity. SA antiretroviral therapy (ART) guidelines recommend creatinine monitoring at baseline (ART start) and at 3, 6 and 12 months, and substituting tenofovir with zidovudine, stavudine or abacavir should creatinine clearance (CrCl) decrease to <50 mL/min.Objective. To assess clinician compliance with tenofovir monitoring and prescribing guidelines.Methods. We described the proportion of adult patients on tenofovir-based first-line ART who were screened for baseline renal impairment, were monitored according to the SA antiretroviral treatment guidelines, and were switched from tenofovir if renal function declined.Results. We included 13 168 patients who started ART from 2010 to 2012. Creatinine concentrations were recorded in 11 712 (88.9%) patients on tenofovir at baseline, 9 135/11 657 (78.4%) at 3 months, 5 426/10 554 (51.4%) at 6 months, and 5 949/ 8 421 (70.6%) at 12 months. At baseline, 227 (1.9%) started tenofovir despite a CrCl <50 mL/min. While on tenofovir, 525 patients had at least one CrCl of <50 mL/min. Of 382 patients with ≥3 months’ follow-up after a CrCl <50 mL/min, 114 (29.8%) stopped tenofovir within 3 months. Clinicians were more likely to stop tenofovir in patients with lower CrCl and CD4 count. Of 226 patients who continued to receive tenofovir and had further CrCls available, 156 (69.0%) had a CrCl ≥50 mL/min at their next visit.Conclusions. Creatinine monitoring is feasible where access to laboratory services is good. Kidney function recovered in most patients who continued to receive tenofovir despite a CrCl <50 mL/min. Further research is needed to determine how best to monitor renal function with tenofovir in resource-limited settings

AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa

BACKGROUND: AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART) and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. METHODS: We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. RESULTS: Of 6292 patients, 215 (3.4%) had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65%) and on the lower extremities (56%). One quarter of patients did not receive cART. The mortality and lost-to-follow-up rates were, respectively, 25 (95% CI 19-32) and eight (95% CI 5-13) per 100 person years for patients who received cART, and 70 (95% CI 42-117) and 119 (80-176) per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p < 0.001), advanced S stage (AHR = 5.1, p = 0.008), and absence of chemotherapy (AHR = 2.4, p = 0.012) were associated with mortality.Patients with AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS-associated Kaposi's sarcoma likely included late diagnosis of HIV disease, late accessibility to cART, and sub-optimal treatment of advanced Kaposi's sarcoma. CONCLUSIONS: These findings confirm the importance of early access to both cART and chemotherapy for patients with AIDS-associated Kaposi's sarcoma. Early diagnosis and improved treatment protocols in resource-poor settings are essential

Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort

Abstract Background We previously reported that one-third of HIV-positive adults requiring medical admission to a South African district hospital had laboratory-confirmed tuberculosis (TB) and that almost two-thirds of cases could be rapidly diagnosed using Xpert MTB/RIF-testing of concentrated urine samples obtained on the first day of admission. Implementation of urine-based, routine, point-of-care TB screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, such as the Determine TB-LAM lateral-flow rapid test for HIV-associated TB. Methods Sputum, urine and blood samples were systematically obtained from unselected HIV-positive adults within 24 hours of admission to a South African township hospital. Additional clinical samples were obtained during hospitalization as clinically indicated. TB was defined by the detection of Mycobacterium tuberculosis in any sample using Xpert MTB/RIF or liquid culture. The diagnostic yield, accuracy and prognostic value of urine-lipoarabinomannan (LAM) testing were determined, but urine-LAM results did not inform treatment decisions. Results Consecutive HIV-positive adult acute medical admissions not already receiving TB treatment (n = 427) were enrolled regardless of clinical presentation or symptoms. TB was diagnosed in 139 patients (TB prevalence 32.6%; median CD4 count 80 cells/μL). In the first 24 hours of admission, sputum (spot and/or induced) samples were obtained from 37.0% of patients and urine samples from 99.5% of patients (P < 0.001). The diagnostic yields from these specimens were 19.4% (n = 27/139) for sputum-microscopy, 26.6% (n = 37/139) for sputum-Xpert, 38.1% (n = 53/139) for urine-LAM and 52.5% (n = 73/139) for sputum-Xpert/urine-LAM combined (P < 0.01). Corresponding yields among patients with CD4 counts <100 cells/μL were 18.9%, 24.3%, 55.4% and 63.5%, respectively (P < 0.01). The diagnostic yield of urine-LAM was unrelated to respiratory symptoms, and LAM assay specificity (using a grade-2 cut-off) was 98.9% (274/277; 95% confidence interval [CI] 96.9–99.8). Among TB cases, positive urine-LAM status was strongly associated with mortality at 90 days (adjusted hazard ratio 4.20; 95% CI 1.50–11.75). Conclusions Routine testing for TB in newly admitted HIV-positive adults using Determine TB-LAM to test urine provides major incremental diagnostic yield with very high specificity when used in combination with sputum testing and has important utility among those without respiratory TB symptoms and/or unable to produce sputum. The assay also rapidly identifies individuals with a poor prognosis

Cryptococcal Antigen Screening in Patients Initiating ART in South Africa: A Prospective Cohort Study.

BACKGROUND: Retrospective data suggest that cryptococcal antigen (CrAg) screening in patients with late-stage human immunodeficiency virus (HIV) initiating antiretroviral therapy (ART) may reduce cryptococcal disease and deaths. Prospective data are limited. METHODS: CrAg was measured using lateral flow assays (LFA) and latex agglutination (LA) tests in 645 HIV-positive, ART-naive patients with CD4 counts ≤100 cells/µL in Cape Town, South Africa. CrAg-positive patients were offered lumbar puncture (LP) and treated with antifungals. Patients were started on ART between 2 and 4 weeks and followed up for 1 year. RESULTS: A total of 4.3% (28/645) of patients were CrAg positive in serum and plasma with LFA. These included 16 also positive by urine LFA (2.5% of total screened) and 7 by serum LA (1.1% of total). In 4 of 10 LFA-positive cases agreeing to LP, the cerebrospinal fluid (CSF) CrAg LFA was positive. A positive CSF CrAg was associated with higher screening plasma/serum LFA titers.Among the 28 CrAg-positive patients, mortality was 14.3% at 10 weeks and 25% at 12 months. Only 1 CrAg-positive patient, who defaulted from care, died from cryptococcal meningitis (CM). Mortality in CrAg-negative patients was 11.5% at 1 year. Only 2 possible CM cases were identified in CrAg-negative patients. CONCLUSIONS: CrAg screening of individuals initiating ART and preemptive fluconazole treatment of CrAg-positive patients resulted in markedly fewer cases of CM compared with historic unscreened cohorts. Studies are needed to refine management of CrAg-positive patients who have high mortality that does not appear to be wholly attributable to cryptococcal disease