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The conduct of Phase I/II HIV vaccine trials internationally necessitates the development of region-specific clinical reference ranges for trial enrollment and participant monitoring. A population based cohort of adults in Kericho, Kenya, a potential vaccine trial site, allowed development of clinical laboratory reference ranges. Lymphocyte immunophenotyping was performed on 1293 HIV seronegative study participants. Hematology and clinical chemistry were performed on up to 1541 cohort enrollees. The ratio of males to females was 1.9:1. Means, medians and 95% reference ranges were calculated and compared with those from other nations. The median CD4+ T cell count for the group was 810 cells/microl. There were significant gender differences for both red and white blood cell parameters. Kenyan subjects had lower median hemoglobin concentrations (9.5 g/dL; range 6.7-11.1) and neutrophil counts (1850 cells/microl; range 914-4715) compared to North Americans. Kenyan clinical chemistry reference ranges were comparable to those from the USA, with the exception of the upper limits for bilirubin and blood urea nitrogen, which were 2.3-fold higher and 1.5-fold lower, respectively. This study is the first to assess clinical reference ranges for a highland community in Kenya and highlights the need to define clinical laboratory ranges from the national community not only for clinical research but also care and treatment.

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.

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. 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. 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). 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. ClinicalTrials.gov NCT01791556.

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. 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. 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). ClinicalTrials.gov NCT00089505.

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.

HIV vaccine trials generally require that pregnant women are excluded from participation, and contraceptive methods must be used to prevent pregnancy during the trial. However, access to quality services and misconceptions associated with contraceptive methods may impact on their effective use in developing countries. We describe the pattern of contraceptive use in a multi-site phase I/IIa HIV Vaccine trial in East Africa (Uganda, Kenya and Tanzania) and factors that may have influenced their use during the trial. Pregnancy prevention counseling was provided to female participants during informed consent process and at each study visit. Participants' methods of contraception used were documented. Methods of contraceptives were provided on site. Pregnancy testing was done at designated visits during the trial. Obstacles to contraceptive use were identified and addressed at each visit. Overall, 103 (31.8%) of a total of 324 enrolled volunteers were females. Female participants were generally young with a mean age of 29(+/-7.2), married (49.5%) and had less than high school education (62.1%). Hormonal contraceptives were the most common method of contraception (58.3%) followed by condom use (22.3%). The distribution of methods of contraception among the three sites was similar except for more condom use and less abstinence in Uganda. The majority of women (85.4%) reported to contraceptive use prior to screening. The reasons for not using contraception included access to quality services, insufficient knowledge of certain methods, and misconceptions. Although hormonal contraceptives were frequently used by females participating in the vaccine trial, misconceptions and their incorrect use might have led to inconsistent use resulting in undesired pregnancies. The study underscores the need for an integrated approach to pregnancy prevention counseling during HIV vaccine trials. ClinicalTrials.gov NCT00123968.

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. Cette étude a exploré les perceptions envers l'utilisation de la contraception chez les femmes séropositives qui sont en âge de procréer, à Kericho, une région qui a un taux élevé de prévalence du VIH et un taux bas de prévalence contraceptive. On s'est servi des méthodes qualitatives dans trois discussions à groupe cible et 15 interviews en profondeur pour collecter des données des 46 femmes séropositives âgées de 18 à 45 ans sélectionnées de manière calculée d'après l'âge. L'analyse a été faite à l'aide d'ATLAS-ti (Centre d » ATLAS-ti, Berlin). La plupart des participants ont indiqué une familiarité avec les contraceptifs modernes. Les participants ont en général aperçu que les hommes se sont opposés à la contraception. Certaines femmes ont indiqué que leur état séropositif a dicté les décisions contraceptives, surtout à l'égard de l'abstinence. Les femmes ont signalé l'interruption des méthodes à cause des effets secondaires, ayant satisfait la parité désirée et des modifications menstruelles Les résultats ont suggéré que les perceptions par rapport aux effets secondaires, les opinions du partenaire maie et la progression de la maladie du VIH jouent des rôles dans les décisions contraceptives. L'assistance socio-psychologique peut dissiper l'information incorrecte et optimiser la pratique contraceptive dans ce milieu.

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.

Objective. To describe TB/HIV clinic outcomes in a rural, Ministry of Health hospital. Design. Retrospective, secondary analyses. Descriptive statistics and logistic regression analyses evaluated baseline characteristics and outcomes. Results. Of 1,911 patients, 89.8% were adults aged 32.0 (±12.6) years with baseline CD4=243.3 (±271.0), 18.2% < 50 cells/mm3. Pulmonary (84.8%, (32.2% smear positive)) exceeded extrapulmonary TB (15.2%). Over 5 years, treatment success rose from 40.0% to 74.6%, lost to follow-up dropped from 36.0% to 12.5%, and deaths fell from 20.0% to 5.4%. For patients starting ART after TB treatment, those with CD4 ≥ 50 cells/mm3 were twice as likely to achieve treatment success (OR=2.0, 95% CI = 1.3–3.1) compared to those with CD4 < 50 cells/mm3. Patients initiating ART at/after 2 months were twice as likely to achieve treatment success (OR=2.0, 95% CI = 1.3–3.3). Yearly, odds of treatment success improved by 20% (OR=1.2, 95% CI = 1.0–1.5). Conclusions. An integrated TB/HIV clinic with acceptable outcomes is a feasible goal in resource-limited settings.

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. Facteurs qui influent sur le choix et l'interruption du contraceptif chez les femmes séropositives à Kericho, Kenya Cette étude a exploré les perceptions envers l'tilisation de la contraception chez les femmes séropositives qui sont en âge de procréer, à Kericho, une région qui a un taux élevé de prévalence du VIH et un taux bas de prévalence contraceptive. On s'est servi des méthodes qualitatives dans trois discussions à groupe cible et 15 interviews en profondeur pour collecter des données des 46 femmes séropositives âgées de 18 à 45 ans sélectionnées de manière calculée d'après l'âge. L'analyse a été faite à l'aide d'ATLAS-ti (Centre d »ATLAS-ti, Berlin). La plupart des participants ont indiqué une familiarité avec les contraceptifs modernes. Les participants ont en général aperçu que les hommes se sont opposés à la contraception. Certaines femmes ont indiqué que leur état séropositif a dicté les décisions contraceptives, surtout à l'égard de l'abstinence. Les femmes ont signalé l'interruption des méthodes à cause des effets secondaires, ayant satisfait la parité désirée et des modifications menstruelles Les résultats ont suggéré que les perceptions par rapport aux effets secondaires, les opinions du partenaire male et la progression de la maladie du VIH jouent des rôles dans les décisions contraceptives. L'assistance socio-psychologique peut dissiper l'information incorrecte et optimiser la pratique contraceptive dans ce milieu.