Juan Sierra-Madero

Metabolic Acidosis and Hepatic Steatosis in Two HIV-Infected Patients on Stavudine (d4T) Treatment

Nucleoside analog reverse transcriptase inhibitors (NRTI) have been used to treat HIV-infected patients for >10 years. Some severe adverse events have been attributed to mitochondrial dysfunction. Since 1991, cases of severe lactic acidosis have been reported in association with nucleoside therapy. Our objective was to report two cases of metabolic acidosis and hepatic steatosis in patients receiving stavudine (d4T) and to review the literature. A male and a female, 47 and 45 years of age, respectively, presented with abdominal pain, nausea, vomiting, and weakness after 9 and 6 months, respectively, of treatment with stavudine. At presentation, both patients had severe metabolic acidosis and liver failure. Ultrasonography showed hepatic steatosis (confirmed by biopsy in one case). All antiretroviral drugs were withdrawn and patients were treated with bicarbonate. Both patients developed fulminant liver dysfunction and multiple organ failure. We reviewed the literature and found 75 cases of lactic acidosis and hepatic steatosis associated with use of NRTI; 57 of these patients received d4T (76%). Of all cases reported in association with nucleoside therapy, 63% were females and mortality was 47%. General weakness, hepatic enzyme elevation, and liver steatosis are data that should alert physicians to this serious adverse event and to respond with prompt interruption of antiretroviral drugs and measurement of lactic acid in plasma. It is important to report serious adverse events in commercially released drugs to know prevalence in an exposed population. Physicians should be aware of risk and early signs of this serious adverse event.

Transfusion-associated HIV infection in Mexico related to paid blood donors; HIV epidemic.

The objective of the study was to describe the clinical, epidemiological profile and conditional incubation period in a group of transfusion-associated HIV-infected (TAHI) patients seen in five national tertiary care centres in Mexico from 1983 to April 1998. Date of transfusions, AIDS diagnoses, opportunistic infections and malignancies were collected. The incubation period was estimated through a non-parametric conditional analysis. One hundred and fifty-seven TAHI cases were analysed. The frequency of TAHI by year of transfusion was: 0.6% in 1980 and 1981, 4.5% in 1984, 22.4% in 1985, 54.5% in 1986, 10.3% in 1987, 0.6% in 1988, 1.9% in 1989 and 1990, 1.3% in 1993 and 0.6% in 1994 and 1996. The median incubation period was 4.3 years. A well-defined epidemic period of HIV-infection among blood-recipients was identified that coincided with the HIV-epidemic among paid donors. TAHI patients in Mexico developed AIDS in a shorter time than that described for other populations.

Changing Risk Factors for HIV Infection

BACKGROUNDnHIV infection in women is a growing problem in developing countries. Risk factors for HIV infection vary from country to country and may change with time.nnnMETHODSnWe describe a retrospective review of the epidemiologic characteristics and associated gynecologic diseases of all HIV-infected women seen at two tertiary-care hospitals in Mexico City.nnnRESULTSnOne hundred thirty consecutive patients were included in the study from March 1985 to January 1996. Mean age at HIV diagnosis was 36.2 years (range: 16-76). Of the 75 women diagnosed with AIDS prior to 1992, 58 (69%) were infected through blood transfusion and 17 (20%) through sexual contact. After January 1992, 11 (23%) acquired infection through blood transfusion and 28 (60%) through sexual contact; these differences were statistically significant (p <0.0001). Prior to 1992, 66 (90%) women presented in stage IV, whereas after that year only 29 (51%) (p <0.001) presented in stage IV. Of 92 patients on whom a cervico-vaginal smear was carried out, human papillomavirus infection was identified in 22 (24%) women, nine (9.8%) had morphologic evidence of a cervical intraepithelial neoplasia (four with mild or moderate dysplasia and five with in situ cervical carcinoma). Four patients had invasive cervical carcinoma.nnnCONCLUSIONSnThe main risk factor for HIV infection in Mexican women with AIDS changed from transfusion acquired to sexually acquired in 1992. As a country, we were successful in providing safe blood but failed to prevent sexual transmission. Our patients had a high frequency of cervical carcinoma and precursor lesions associated with human papilloma virus.

Time to HAART Initiation after Diagnosis and Treatment of Opportunistic Infections in Patients with AIDS in Latin America

Background Since 2009, earlier initiation of highly active antiretroviral therapy (HAART) after an opportunistic infection (OI) has been recommended based on lower risks of death and AIDS-related progression found in clinical trials. Delay in HAART initiation after OIs may be an important barrier for successful outcomes in patients with advanced disease. Timing of HAART initiation after an OI in “real life” settings in Latin America has not been evaluated. Methods Patients in the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet) ≥18 years of age at enrolment, from 2001–2012 who had an OI before HAART initiation were included. Patients were divided in an early HAART (EH) group (those initiating within 4 weeks of an OI) and a delayed HAART (DH) group (those initiating more than 4 weeks after an OI). All patients with an AIDS-defining OI were included. In patients with more than one OI the first event reported was considered. Calendar trends in the proportion of patients in the EH group (before and after 2009) were estimated by site and for the whole cohort. Factors associated with EH were estimated using multivariable logistic regression models. Results A total of 1457 patients had an OI before HAART initiation and were included in the analysis: 213 from Argentina, 686 from Brazil, 283 from Chile, 119 from Honduras and 156 from Mexico. Most prevalent OI were Tuberculosis (31%), followed by Pneumocystis pneumonia (24%), Invasive Candidiasis (16%) and Toxoplasmosis (9%). Median time from OI to HAART initiation decreased significantly from 5.7 (interquartile range [IQR] 2.8–12.1) weeks before 2009 to 4.3 (IQR 2.0–7.1) after 2009 (p<0.01). Factors associated with starting HAART within 4 weeks of OI diagnosis were lower CD4 count at enrolment (p-<0.001), having a non-tuberculosis OI (p<0.001), study site (p<0.001), and more recent years of OI diagnosis (p<0.001). Discussion The time from diagnosis of an OI to HAART initiation has decreased in Latin America coinciding with the publication of evidence of its benefit. We found important heterogeneity between sites which may reflect differences in clinical practices, local guidelines, and access to HAART. The impact of the timing of HAART initiation after OI on patient survival in this “real life” context needs further evaluation.

Clinical outcomes of first-line antiretroviral therapy in Latin America: analysis from the LATINA retrospective cohort study

Nearly 2 million people are infected with human immunodeficiency virus (HIV) in Latin America. However, information regarding population-scale outcomes from a regional perspective is scarce. We aimed to describe the baseline characteristics and therapeutic outcomes of newly-treated individuals with HIV infection in Latin America. A Retrospective cohort study was undertaken. The primary explanatory variable was combination antiretroviral therapy based on either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The main outcome was defined as the composite of all-cause mortality and the occurrence of an AIDS-defining clinical event or a serious non-AIDS-defining event during the first year of therapy. The secondary outcomes included the time to a change in treatment strategy. All analyses were performed according to the intention to treat principle. A total of 937 treatment-naive patients from four participating countries were included (228 patients with PI therapy and 709 with NNRTI–based treatment). At the time of treatment initiation, the patients had a mean age of 37 (SD: 10) years and a median CD4u2009+u2009T-cell count of 133 cells/mm3 (interquartile range: 47.5–216.0). Patients receiving PI-based regimens had a significantly lower CD4u2009+u2009count, a higher AIDS prevalence at baseline and a shorter time from HIV diagnosis until the initiation of treatment. There was no difference in the hazard ratio for the primary outcome between groups. The only covariates associated with the latter were CD4u2009+u2009cell count at baseline, study site and age. The estimated hazard ratio for the time to a change in treatment (NNRTI vs PI) was 0.61 (95% CI 0.47–0.80, pu2009<u20090.01). This study concluded that patients living with HIV in Latin America present with similar clinical outcomes regardless of the choice of initial therapy. Patients treated with PIs are more likely to require a treatment change during the first year of follow up.

Virologic failure and mortality in older ART initiators in a multisite Latin American and Caribbean Cohort

The “greying” of the HIV epidemic necessitates a better understanding of the healthcare needs of older HIV‐positive adults. As these individuals age, it is unclear whether comorbidities and their associated therapies or the ageing process itself alter the response to antiretroviral therapy (ART). In this study, HIV treatment outcomes and corresponding risk factors were compared between older ART initiators and those who were younger using data from the Caribbean, Central and South America Network for HIV Epidemiology (CCASAnet).

A decade of HAART in Latin America: Long term outcomes among the first wave of HIV patients to receive combination therapy.

Background In Latin America, the first wave of HIV-infected patients initiated highly active antiretroviral therapy (HAART) 10 or more years ago. Characterizing their treatment experience and corresponding outcomes across a decade of HAART may yield insights relevant to the ongoing care of such patients and those initiating HAART more recently in similar clinical settings. Methods This retrospective study included adults initiating HAART before 2004 at 8 sites in Argentina, Brazil, Chile, Haiti, Honduras, and Mexico. Patient status (in care, dead, or lost to follow-up [LTFU]) was assessed at 6-month intervals for 10 years, along with CD4 count and HIV-1 viral load (VL) for patients in care. Results 4,975 patients (66% male) started HAART prior to 2004; 45% were not antiretroviral-naïve. At 1, 5, and 10 years, rates of mortality were 4.2%, 9.0%, and 13.6% respectively. LTFU rates for the same periods were 2.4%, 10.9%, and 24.2%. Among patients remaining in care at 10 years, 84.4% were estimated to have VL≤400 copies/mL (Haiti excluded) and median baseline CD4 increased from 158 to 525 cells/mm3. Only 11.4% of all patients remained on their first regimen, 12.6% were on their second, 11.5% were on their third, and 23.0% were on their fourth or subsequent regimen. Outcomes were generally better for patients who were not antiretroviral-naïve, except for viral suppression. Heterogeneity among sites was substantial. Conclusions Despite advanced disease and predominant use of older antiretrovirals, a large percentage of early HAART initiators in this Latin American cohort were alive and in care with sustained virologic suppression and progressive immune recovery after 10 years.