Prospective International Study of Incidence and Predictors of Immune Reconstitution Inflammatory Syndrome and Death in People Living With Human Immunodeficiency Virus and Severe Lymphopenia.

BACKGROUND: Patients living with human immunodeficiency virus (PLWH) with low CD4 counts are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death at antiretroviral therapy (ART) initiation. METHODS: We investigated the clinical impact of IRIS in PLWH and CD4 counts <100 cells/µL starting ART in an international, prospective study in the United States, Thailand, and Kenya. An independent review committee adjudicated IRIS events. We assessed associations between baseline biomarkers, IRIS, immune recovery at week 48, and death by week 48 with Cox models. RESULTS: We enrolled 506 participants (39.3% were women). Median age was 37 years, and CD4 count was 29 cells/µL. Within 6 months of ART, 97 (19.2%) participants developed IRIS and 31 (6.5%) died. Participants with lower hemoglobin at baseline were at higher IRIS risk (hazard ratio [HR], 1.2; P = .004). IRIS was independently associated with increased risk of death after adjustment for known risk factors (HR, 3.2; P = .031). Being female (P = .004) and having a lower body mass index (BMI; P = .003), higher white blood cell count (P = .005), and higher D-dimer levels (P = .044) were also significantly associated with increased risk of death. Decision-tree analysis identified hemoglobin <8.5 g/dL as predictive of IRIS and C-reactive protein (CRP) >106 µg/mL and BMI <15.6 kg/m2 as predictive of death. CONCLUSIONS: For PLWH with severe immunosuppression initiating ART, baseline low BMI and hemoglobin and high CRP and D-dimer levels may be clinically useful predictors of IRIS and death risk.

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

BACKGROUND: A 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. METHODS: This 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. RESULTS: The 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. CONCLUSION: After 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 REGISTRATION: Clinicaltrials.gov Identifier: NCT00089505.

Antiretroviral therapies in women after single-dose nevirapine exposure.

BACKGROUND: Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus. METHODS: In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir­emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death. RESULTS: A total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P=0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died. CONCLUSIONS: In women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir­emtricitabine was superior to nevirapine plus tenofovir­emtricitabine for initial antiretroviral therapy. (Funded by the National Institute of Allergy and Infectious Diseases and the National Research Center; ClinicalTrials.gov number, NCT00089505.).

Nevirapine- versus lopinavir/ritonavir-based initial therapy for HIV-1 infection among women in Africa: a randomized trial.

BACKGROUND: Nevirapine (NVP) is widely used in antiretroviral treatment (ART) of HIV-1 globally. The primary objective of the AA5208/OCTANE trial was to compare the efficacy of NVP-based versus lopinavir/ritonavir (LPV/r)-based initial ART. METHODS AND FINDINGS: In seven African countries (Botswana, Kenya, Malawi, South Africa, Uganda, Zambia, and Zimbabwe), 500 antiretroviral-naïve HIV-infected women with CD4<200 cells/mm(3) were enrolled into a two-arm randomized trial to initiate open-label ART with tenofovir (TDF)/emtricitabine (FTC) once/day plus either NVP (n = 249) or LPV/r (n = 251) twice/day, and followed for ≥48 weeks. The primary endpoint was time from randomization to death or confirmed virologic failure ([VF]) (plasma HIV RNA<1 log(10) below baseline 12 weeks after treatment initiation, or ≥400 copies/ml at or after 24 weeks), with comparison between treatments based on hazard ratios (HRs) in intention-to-treat analysis. Equivalence of randomized treatments was defined as finding the 95% CI for HR for virological failure or death in the range 0.5 to 2.0. Baseline characteristics were (median): age = 34 years, CD4 = 121 cells/mm(3), HIV RNA = 5.2 log(10)copies/ml. Median follow-up = 118 weeks; 29 (6%) women were lost to follow-up. 42 women (37 VFs, five deaths; 17%) in the NVP and 50 (43 VFs, seven deaths; 20%) in the LPV/r arm reached the primary endpoint (HR 0.85, 95% CI 0.56-1.29). During initial assigned treatment, 14% and 16% of women receiving NVP and LPV/r experienced grade 3/4 signs/symptoms and 26% and 22% experienced grade 3/4 laboratory abnormalities. However, 35 (14%) women discontinued NVP because of adverse events, most in the first 8 weeks, versus none for LPV/r (p<0.001). VF, death, or permanent treatment discontinuation occurred in 80 (32%) of NVP and 54 (22%) of LPV/r arms (HR = 1.7, 95% CI 1.2-2.4), with the difference primarily due to more treatment discontinuation in the NVP arm. 13 (45%) of 29 women tested in the NVP versus six (15%) of 40 in the LPV/r arm had any drug resistance mutation at time of VF. CONCLUSIONS: Initial ART with NVP+TDF/FTC demonstrated equivalent virologic efficacy but higher rates of treatment discontinuation and new drug resistance compared with LPV/r+TDF/FTC in antiretroviral-naïve women with CD4<200 cells/mm(3). TRIAL REGISTRATION: ClinicalTrials.gov NCT00089505.

Brief Report: No Differences Between Lopinavir/Ritonavir and Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy on Clearance of Plasmodium falciparum Subclinical Parasitemia in Adults Living With HIV Starting Treatment (A5297).

BACKGROUND: HIV protease inhibitors anti-Plasmodium falciparum activity in adults remains uncertain. METHODS: Adults with HIV CD4+ counts >200 cells/mm3 starting antiretroviral therapy (ART) with P. falciparum subclinical parasitemia (Pf SCP) were randomized 1:1 to (step 1) protease inhibitor lopinavir/ritonavir (LPV/r)-based (arm A) or nonnucleoside reverse transcriptase inhibitor (nNRTI)-based ART (arm B) for 15 days. In step 2, participants received nNRTI-based ART and trimethoprim/sulfamethoxazole prophylaxis for 15 days. P. falciparum SCP clearance was measured by polymerase chain reaction. The Fisher exact test [95% exact confidence interval (CI)] was used to compare proportions of P. falciparum SCP clearance (<10 parasites/µL on 3 occasions within 24 hours) between LPV/r and nNRTI arms at day 15. The Kaplan-Meier method and log-rank test were used to compare time-to-clearance. RESULTS: Fifty-two adults from Kenya, Malawi, and Uganda with a median age = 31 (Q1, Q3: 24-39) years, 33% women, with baseline median CD4+ counts of 324 (259-404) cells/mm3, median HIV-1 RNA viremia of 5.18 log10 copies/mL (4.60-5.71), and median estimated P. falciparum density of 454 parasites/µL (83-2219) enrolled in the study. Forty-nine (94%) participants completed the study. At day 15, there was no statistically significant difference in the proportions of P. falciparum SCP clearance between the LPV/r (23.1% clearance; 6 of the 26) and nNRTI (26.9% clearance; 7 of the 26) arms [between-arm difference 3.9% (95% CI, -21.1% to 28.4%; P = 1.00)]. No significant difference in time-to-clearance was observed between the arms (P = 0.80). CONCLUSIONS: In a small randomized study of adults starting ART with P. falciparum SCP, no statistically significant differences were seen between LPV/r- and nNRTI-based ART in P. falciparum SCP clearance after 15 days of treatment.

Association between severe anaemia and inflammation, risk of IRIS and death in persons with HIV: A multinational cohort study.

BACKGROUND: After initiating antiretroviral therapy (ART), approximately 25% of people with HIV (PWH) may develop Immune Reconstitution Inflammatory Syndrome (IRIS), which is associated with increased morbidity and mortality. Several reports have demonstrated that low haemoglobin (Hb) levels are a risk factor for IRIS. To what extent the severity of anaemia contributes to the risk of IRIS and/or death is still insufficiently explored. METHODS: We investigated both the presence and severity of anaemia in PWH in a multinational cohort of ART-na..ve patients. A large panel of plasma biomarkers was measured pre-ART and patients were followed up for 6 months. IRIS or deaths during this period were considered as outcomes. We performed multidimensional analyses, logistic regression, and survival curves to delineate associations. FINDINGS: Patients with severe anaemia (SA) presented a distinct systemic inflammatory profile, characterized by higher TNF, IL-6, and IL-27 levels. SA was independently associated with IRIS, with a higher risk of both early IRIS onset and death. Among IRIS patients, those with SA had a higher risk of mycobacterial IRIS. INTERPRETATION: PWH with SA display a more pronounced inflammatory profile, with an elevated risk of developing IRIS earlier and a statistically significant higher risk of death. FUNDING: Intramural Research Program of National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH). Coordena...·o de Aperfei..oamento de Pessoal de N.ível Superior (Finance code: 001) and the Conselho Nacional de Desenvolvimento Cient.ífico e Tecnol..gico (CNPq), Brazil.

Influence of culture on contraceptive utilization among HIV-positive women in Brazil, Kenya, and South Africa.

Contraceptive choice and discontinuation are poorly understood among HIV-positive women, and HIV disease and culture may influence decisions. We assessed factors influencing contraceptive decision-making among HIV-positive women in three countries. This qualitative assessment of 108 HIV-positive women (36/site, selected by age and parity strata) was conducted in Rio de Janeiro, Brazil; Kericho, Kenya; and Soweto, South Africa. Freelist interviews assessed knowledge and attitudes towards contraception and were analyzed enumerating frequency and saliency of mentions. There was intersite consensus around list items but priority and themes varied. Site-specific factors influencing contraceptive choice were male partner wishes and fertility desire (Brazil), side-effects (South Africa), and impact on health and HIV progression (Kenya). Age, parity, and taking antiretroviral therapy (ART) impacted some themes. Contraceptive use among HIV-positive women is substantially influenced by culture and other factors. Counseling efforts should consider individual factors in method selection and offer method variety to accommodate changing needs.

A phase 1/2 study of a multiclade HIV-1 DNA plasmid prime and recombinant adenovirus serotype 5 boost vaccine in HIV-Uninfected East Africans (RV 172).

BACKGROUND: Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multiclade DNA vaccine prime with a replication-defective recombinant adenovirus serotype 5 (rAd5) boost. METHODS: The vaccine is a 6-plasmid mixture encoding HIV envelope (env) subtypes A, B, and C and subtype B gag, pol, and nef, and an rAd5 expressing identical genes, with the exception of nef. Three hundred and twenty-four participants were randomized to receive placebo (n=138), a single dose of rAd5 at 10(10) (n = 24) or 10(11) particle units (n = 24), or DNA at 0, 1, and 2 months, followed by rAd5 at either 10(10) (n= 114) or 10(11) particle units (n = 24) boosting at 6 months. Participants were followed up for 24 weeks after the final vaccination. RESULTS: The vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccinees. Titers of preexisting Ad5 neutralizing antibody did not affect the frequency and magnitude of T cell responses in prime-boost recipients but did affect the response rates in participants that received rAd5 alone (P = .037). CONCLUSION: The DNA/rAd5 vaccination regimen was safe and induced HIV type 1 multi-clade T cell responses, which were not significantly affected by titers of preexisting rAd5 neutralizing antibody. Trial Registration. ClinicalTrials.gov identifier: NCT00123968 .

Attaining 95-95-95 through Implementation Science: 15 Years of Insights and Best Practices from the Walter Reed Army Institute of Research's Implementation of the U.S. President's Emergency Plan for AIDS Relief.

The Walter Reed Army Institute of Research (WRAIR) supports more than 350,000 people on lifesaving HIV treatment in Kenya, Nigeria, Tanzania, and Uganda through funding from the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Here, we review and synthesize the range of impacts WRAIR's implementation science portfolio has had on PEPFAR service delivery for military and civilian populations since 2003. We also explore how investments in implementation science create institutional synergies within the U.S. Department of Defense, contributing to broad global health engagements and improving health outcomes for populations served. Finally, we discuss WRAIR's contributions to PEPFAR priorities through use of data to drive and improve programming in real time in the era of HIV epidemic control and public health messaging that includes prevention, the 95-95-95 goals, and comorbidities.

Improvements in physical wellbeing over the first two years on antiretroviral therapy in western Kenya.

Improvements in physical wellbeing during the first six months on antiretroviral therapy (ART) are well known, but little is known regarding long-term follow-up. We conducted a prospective cohort study among 222 HIV-positive adult tea plantation workers in western Kenya to assess wellbeing over their first two years on ART. Study subjects completed a standardized questionnaire during repeat ART clinic visits. A 30-day recall period was used to elicit the number of days when subjects experienced poor health and the number of days that pain made it difficult to complete usual activities at home and work. A seven-day recall period was used to assess the severity of bodily pain, nausea, fatigue, and rash. Prevalence of most symptoms declined over time. A median of seven days poor health during the first month on ART declined to three days in the 24th month (p=0.043). For pain making usual activities difficult, a median of seven days during the first month on ART fell to zero by 12 months (p< or =0.0001) but increased to three days by two years. Any bodily pain (range 59-83%) and fatigue (range 51-84%) over the past seven days were common through two years. However, pain and fatigue often over the past seven days declined over two years (from 24-10% (p=0.067) and 41-15% (p=0.002)). Skin rash was rare at all times, though higher at two years (8.6%) than any other time. Initial improvements in physical wellbeing were sustained over two years, however, increased pain and skin rash at year two may indicate problems as treatment programs mature. These improvements in physical wellbeing will be important in sustaining the long-term success of HIV treatment programs.

Factors influencing contraceptive choice and discontinuation among HIV-positive women in Kericho, Kenya.

This study explored perceptions towards and utilization of contraception among HIV-positive, reproduction-age women in Kericho, Kenya, an area with high HIV and low contraceptive prevalence rates. Qualitative methods were used in three focus group discussions and 15 in-depth interviews to gather data from 46 HIV-positive women ages 18 to 45, purposively selected by age strata. Analysis was performed using ATLAS-ti (ATLAS-ti Center, Berlin). Most participants reported familiarity with modern contraceptives. Participants generally perceived that men opposed contraception. Some women indicated that their HIV status dictated contraceptive decisions, particularly with regard to abstinence. Women reported method discontinuation because of side effects, having met desired parity, and menstrual changes. Findings suggested that perceptions about side effects, opinions of the male partner, and HIV disease progression play important roles in contraceptive decisions. Counseling can dispel incorrect information and optimize contraceptive practice in this setting.

Do the socioeconomic impacts of antiretroviral therapy vary by gender? A longitudinal study of Kenyan agricultural worker employment outcomes.

BACKGROUND: As access to antiretroviral therapy (ART) has grown in Africa, attention has turned to evaluating the socio-economic impacts of ART. One key issue is the extent to which improvements in health resulting from ART allows individuals to return to work and earn income. Improvements in health from ART may also be associated with reduced impaired presenteeism, which is the loss of productivity when an ill or disabled individual attends work but accomplishes less at his or her usual tasks or shifts to other, possibly less valuable, tasks. METHODS: Longitudinal data for this analysis come from company payroll records for 97 HIV-infected tea estate workers (the index group, 56 women, 41 men) and a comparison group of all workers assigned to the same work teams (n = 2485, 1691 men, 794 women) for a 37-month period covering two years before and one year after initiating ART. We used nearest neighbour matching methods to estimate the impacts of HIV/AIDS and ART on three monthly employment outcomes for tea estate workers in Kenya--days plucking tea, days assigned to non-plucking assignments, and kilograms harvested when plucking. RESULTS: The female index group worked 30% fewer days plucking tea monthly than the matched female comparison group during the final 9 months pre-ART. They also worked 87% more days on non-plucking assignments. While the monthly gap between the two groups narrowed after beginning ART, the female index group worked 30% fewer days plucking tea and about 100% more days on non-plucking tasks than the comparison group after one year on ART. The male index group was able to maintain a similar pattern of work as their comparison group except during the initial five months on therapy. CONCLUSION: Significant impaired presenteeism continued to exist among the female index group after one year on ART. Future research needs to explore further the socio-economic implications of HIV-infected female workers on ART being less productive than the general female workforce over sustained periods of time.

Analytical methods used for the discrimination of substances suspected to be bar soap: a preliminary study.

The submission to forensic laboratories of unknown specimens suspected of being biological or chemical warfare agents has increased tremendously with the threat of terrorism. Oftentimes, a threatening correspondence that contains hoax materials is intended to make the recipient(s) believe they have been exposed to a toxin. In some cases, the perpetrator can use standard household products, such as detergents and soaps. Once these materials are received, they become forensic evidence and may be analyzed for identification and/or comparison with known seized material from a suspect(s). Two separate studies were conducted using different analytical protocols for bar soaps. In the first set, the forensic laboratory at the United States Secret Service conducted tests on 68 bars of soap using solid-phase microextraction and gas chromatography coupled with mass spectrometry. The 68 different soaps displayed unique total ion chromatogram profiles. Energy-dispersive X-ray analysis in conjunction with scanning electron microscopy was also used to characterize 46 of the 68 soaps as a preliminary study. In a second set of studies, as part of a homicide investigation, the laboratory at the California Department of Justice, Riverside, conducted examinations on 13 bars of soap by utilizing Fourier transform-infrared spectroscopy. The case study demonstrated that it is possible to distinguish some bar soaps using infrared analysis. Furthermore, the bar soaps could be distinguished from typical laundry detergents using this technique.

An evaluation of matching unknown writing inks with the United States International Ink Library.

Utilizing a database of standards for forensic casework is a valuable resource. Undoubtedly, as more standards (and corresponding information about the specimens) are collected, there is a greater certainty of identification when a questioned and a known item cannot be distinguished after a series of analyses. The United States Secret Service and the Internal Revenue Service National Forensic Laboratory jointly maintain the largest known forensic collection of writing inks in the world, which is comprised of over 8500 ink standards collected worldwide, dating back to the 1920s. This study was conducted to evaluate the reliability of matching arbitrarily purchased pens with known inks from a database. One hundred pens were randomly obtained from a variety of sources and their respective ink compositions were compared with standards. Eighty-five of the inks were determined to be suitable for comparison utilizing optical examinations and thin-layer chromatography. Three of the inks did not match any of the specimens on record; one of these inks was similar to an ink from an identical brand of pen that was in the database, but had a modified formulation.

Fasting and 2-hour postchallenge serum glucose measures and risk of incident cardiovascular events in the elderly: the Cardiovascular Health Study.

BACKGROUND: The contributions of fasting and 2-hour postchallenge glucose level to cardiovascular events remain ill-defined, especially for nondiabetic adults. This study examined the relative predictive power of fasting and 2-hour glucose level on cardiovascular event risk. METHODS: A total of 4014 community-dwelling adults 65 years or older who participated in the baseline visit of the Cardiovascular Health Study and who were without treated diabetes or previous myocardial infarction or stroke were eligible for analyses. Participants with treated diabetes at baseline were excluded. Incident myocardial infarction or stroke, or coronary death, was the outcome of interest. Age-, sex-, and race-adjusted proportional hazards regression models described individual and joint associations between baseline measures of fasting and 2-hour postchallenge glucose level and event risk. RESULTS: There were 764 incident cardiovascular events during 8.5 years of follow-up. Fasting glucose level of 115 mg/dL (6.4 mmol/L) or more was associated with an increased cardiovascular risk (hazard ratio [HR], 1.66 [95% confidence interval (CI), 1.39-1.98]) in adjusted analyses compared with fasting glucose level less than 115 mg/dL. Two-hour glucose level was associated with a linear risk (HR, 1.02 [95% CI, 1.00-1.04] per 10 mg/dL [0.6 mmol/L]) that included an additional increase in risk for 2-hour glucose level of 154 mg/dL (8.5 mmol/L) or more (HR, 1.29 [95% CI, 1.04-1.59]) in adjusted analyses. In joint fasting and 2-hour glucose models, only 2-hour glucose level remained predictive of event risk. CONCLUSIONS: Two-hour glucose level was better than fasting glucose level alone at identifying older adults at increased risk of major incident cardiovascular events.

Kericho CLinic-based ART Diagnostic Evaluation (CLADE): design, accrual, and baseline characteristics of a randomized controlled trial conducted in predominately rural, district-level, HIV clinics of Kenya.

BACKGROUND: Prospective clinical trial data regarding routine HIV-1 viral load (VL) monitoring of antiretroviral therapy (ART) in non-research clinics of Sub-Saharan Africa are needed for policy makers. METHODS: CLinic-based ART Diagnostic Evaluation (CLADE) is a randomized, controlled trial (RCT) evaluating feasibility, superiority, and cost-effectiveness of routine VL vs. standard of care (clinical and immunological) monitoring in adults initiating dual nucleoside reverse transcriptase inhibitor (NRTI)+non-NRTI ART. Participants were randomized (1:1) at 7 predominately rural, non-research, district-level clinics of western Kenya. Descriptive statistics present accrual patterns and baseline cohort characteristics. RESULTS: Over 15 months, 820 adults enrolled at 7 sites with 86-152 enrolled per site. Monthly site enrollment ranged from 2-92 participants. Full (100%) informed consent compliance was independently documented. Half (49.9%) had HIV diagnosed through voluntary counseling and testing. Study arms were similar: mostly females (57.6%) aged 37.6 (SD = 9.0) years with low CD4 (166 [SD = 106]) cells/m3). Notable proportions had WHO Stage III or IV disease (28.7%), BMI <18.5 kg/m2 (23.1%), and a history of tuberculosis (5.6%) or were receiving tuberculosis treatment (8.2%) at ART initiation. In the routine VL arm, 407/409 (99.5%) received baseline VL (234,577 SD = 151,055 copies/ml). All participants received lamivudine; 49.8% started zidovudine followed by 38.4% stavudine and 11.8% tenofovir; and, 64.4% received nevirapine as nNRTI (35.6% efavirenz). CONCLUSIONS: A RCT can be enrolled successfully in rural, non-research, resource limited, district-level clinics in western Kenya. Many adults presenting for ART have advanced HIV/AIDS, emphasizing the importance of universal HIV testing and linkage-to-care campaigns. TRIAL REGISTRATION: ClinicalTrials.gov NCT01791556.

The Number and Complexity of Pure and Recombinant HIV-1 Strains Observed within Incident Infections during the HIV and Malaria Cohort Study Conducted in Kericho, Kenya, from 2003 to 2006.

Characterization of HIV-1 subtype diversity in regions where vaccine trials are conducted is critical for vaccine development and testing. This study describes the molecular epidemiology of HIV-1 within a tea-plantation community cohort in Kericho, Kenya. Sixty-three incident infections were ascertained in the HIV and Malaria Cohort Study conducted in Kericho from 2003 to 2006. HIV-1 strains from 58 of those individuals were full genome characterized and compared to two previous Kenyan studies describing 41 prevalent infections from a blood bank survey (1999-2000) and 21 infections from a higher-risk cohort containing a mix of incident and prevalent infections (2006). Among the 58 strains from the community cohort, 43.1% were pure subtypes (36.2% A1, 5.2% C, and 1.7% G) and 56.9% were inter-subtype recombinants (29.3% A1D, 8.6% A1CD, 6.9% A1A2D, 5.2% A1C, 3.4% A1A2CD, and 3.4% A2D). This diversity and the resulting genetic distance between the observed strains will need to be addressed when vaccine immunogens are chosen. In consideration of current vaccine development efforts, the strains from these three studies were compared to five candidate vaccines (each of which are viral vectored, carrying inserts corresponding to parts of gag, pol, and envelope), which have been developed for possible use in sub-Saharan Africa. The sequence comparison between the observed strains and the candidate vaccines indicates that in the presence of diverse recombinants, a bivalent vaccine is more likely to provide T-cell epitope coverage than monovalent vaccines even when the inserts of the bivalent vaccine are not subtype-matched to the local epidemic.

Concomitant risk factors in reports of torsades de pointes associated with macrolide use: review of the United States Food and Drug Administration Adverse Event Reporting System.

In this case series, we examined concomitant risk factors mentioned in reports of torsades de pointes, a rare ventricular arrhythmia, that occurred in association with administration of macrolide antimicrobials (e.g., azithromycin, clarithromycin, dirithromycin, and erythromycin). Increasing age, female sex, and concomitant diseases and drug administration believed to increase risks for torsades de pointes were commonly reported.

Cardiovascular disease risk factors in HIV-infected women after initiation of lopinavir/ritonavir- and nevirapine-based antiretroviral therapy in Sub-Saharan Africa: A5208 (OCTANE).

BACKGROUND: Limited comparative, prospective data exist regarding cardiovascular risk factors in HIV-infected women starting antiretroviral therapy in Africa. METHODS: In 7 African countries, 741 women with CD4 <200 cells/mm were randomized to tenofovir/emtricitabine (TDF/FTC) plus either nevirapine (NVP, n = 370) or lopinavir/ritonavir (LPV/r, n = 371). Lipids and blood pressure (BP) were evaluated at entry, 48, 96, and 144 weeks. Multivariable linear and logistic regression models were used to evaluate mean risk factor changes and clinically relevant risk factor changes. RESULTS: At entry, both NVP and LPV/r groups were similar regarding age [mean = 33.5 (SD = 7.1) years], CD4 [129 (67) cells/mm], and HIV-1 RNA [5.1 (0.6) log10 copies/mL]. Nearly, all women had normal lipids and BP except for high-density lipoprotein (HDL)-cholesterol. Over 144 weeks, the LPV/r compared with NVP group had significantly greater mean lipid increases (eg, non-HDL: +29 vs. +13 mg/dL) and smaller HDL increases (+12 vs. +21 mg/dL). In contrast, the NVP compared with LPV/r group had greater mean increases in BP (eg, diastolic BP: +5 vs. -0.5 mm Hg). Significantly, more women assigned LPV/r had week 144 "abnormal" lipid levels (eg, HDL 29.7% vs. 14.8% and triglycerides 28.6% vs. 8.2%), and significantly, more women assigned NVP had "abnormal" BP (eg, diastolic BP 22.7% vs. 6.5%). Most differences remained significant when adjusted for baseline risk factor, age, CD4, and HIV-1 RNA. CONCLUSIONS: In HIV-infected women initiating antiretroviral therapy in Africa, LPV/r + TDF/FTC was associated with less favorable changes in lipids, and use of NVP + TDF/FTC was associated with less favorable changes in BP.

ART treatment costs and retention in care in Kenya: a cohort study in three rural outpatient clinics.

INTRODUCTION: After almost 10 years of PEPFAR funding for antiretroviral therapy (ART) treatment programmes in Kenya, little is known about the cost of care provided to HIV-positive patients receiving ART. With some 430,000 ART patients, understanding and managing costs is essential to treatment programme sustainability. METHODS: Using patient-level data from medical records (n=120/site), we estimated the cost of providing ART at three treatment sites in the Rift Valley Province of Kenya (a clinic at a government hospital, a hospital run by a large agricultural company and a mission hospital). Costs included ARV and non-ARV drugs, laboratory tests, salaries to personnel providing patient care, and infrastructure and other fixed costs. We report the average cost per patient during the first 12 months after ART initiation, stratified by site, and the average cost per patient achieving the primary outcome, retention in care 12 months after treatment initiation. RESULTS: The cost per patient initiated on ART was $206, $252 and $213 at Sites 1, 2 and 3, respectively. The proportion of patients remaining in care at 12 months was similar across all sites (0.82, 0.80 and 0.84). Average costs for the subset of patients who remained in care at 12 months was also similar (Site 1, $229; Site 2, $287; Site 3, $237). Patients not retained in care cost substantially less (Site 1, $104; Site 2, $113; Site 3, $88). For the subset of patients who remained in care at 12 months, ART medications accounted for 51%, 44% and 50% of the costs, with the remaining costs split between non-ART medications (15%, 11%, 10%), laboratory tests (14%, 15%, 15%), salaries to personnel providing patient care (9%, 11%, 12%) and fixed costs (11%, 18%, 13%). CONCLUSIONS: At all three sites, 12-month retention in care compared favourably to retention rates reported in the literature from other low-income African countries. The cost of providing treatment was very low, averaging $224 in the first year, less than $20/month. The cost of antiretroviral medications, roughly $120 per year, accounted for approximately half of the total costs per patient retained in care after 12 months.