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The objective of the study was to establish the mother-baby pair characteristics that contribute to vertical transmission of HIV and elucidate on remediation. We assessed for factors increasing the odds of HIV transmission in children born to HIV-infected mothers in western Kenya. We used a retrospective study which reviewed routinely collected data of 1 028 mother-baby pairs enrolled in a prevention of mother-to-child transmission (PMTCT) programme in western Kenya from January to December 2015. We compared the transmission rates amongst mothers known to have a positive HIV status before conception (known positives/KPs) versus the transmission amongst those who were newly diagnosed during maternal and child health (MCH) clinic attendance (new positives/NPs). We compared the socio-demographic and clinical characteristics of the mothers using chi square and Kruskal-Wallis tests at 95% confidence interval (CI). We assessed for factors associated with the infants' HIV status using a logistic regression model. The results revealed that 60% (622) of the mothers were KPs, and that KPs and NPs had mother-to-child transmission (MTCT) rates of 5.5% and 20.7% respectively. Close to 90% of the NP Mothers were at an early HIV clinical stage at enrolment and 40% were enrolled after delivery. The infants of NPs were enrolled at a mean age of 18.3 weeks compared to 6.6 weeks for the infants of the KPs. On adjusted multivariable analysis, child's age at enrolment (AOR = 1.05, 95%CI = 1.036-1.064) and mother's status at conception (AOR = 1.96, 95%CI = 1.042-3.664) were significantly associated with the infant's HIV status. None of the HIV infected infants had received nevirapine prophylaxis. Most of the mothers enrolling into the PMTCT programme have a known HIV-positive status, however, NPs are the largest contributors to continued MTCT.

Thirty-four million people worldwide were living with the HIV by the end of 2010. Despite significant advances in antiretroviral therapy, drug resistance remains a major deterrent to successful, enduring treatment. Unplanned interruptions in antiretroviral therapy have negative effects on HIV treatment outcomes, including increased morbidity and mortality, as well as development of drug resistance. Treatment interruptions due to political conflicts, not infrequent in resource-limited settings, result in disruptions in health care, infrastructure, or treatment facilities and patient displacement. Such circumstances are ideal bases for antiretroviral therapy resistance development, but there is limited awareness of and data available on the association between political conflict and the development of HIV drug resistance. In this review we identify and discuss this association and review how varying antiretroviral therapy half-lives, genetic barriers, different HIV subtypes, and archived resistance can lead to lack of medication effectiveness upon post-conflict resumption of care. Optimized antiretroviral therapy stopping strategies as well as infrastructural concerns and stable HIV treatment systems to ensure continuity of care and rapid resumption of care must be addressed in order to mitigate risks of HIV drug resistance development during and after political conflicts. Increased awareness of such associations by clinicians as well as politicians and stakeholders is essential.

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.

Background: East Africa has experienced a rapid expansion in access to antiretroviral therapy (ART) for HIV-infected patients. Regionally representative socio-demographic, laboratory and clinical characteristics of patients accessing ART over time and across sites have not been well described., Methods: We conducted a cross-sectional analysis of characteristics of HIV-infected adults initiating ART between 2002 and 2009 in Kenya, Uganda and Tanzania and in the International Epidemiologic Databases to Evaluate AIDS Consortium. Characteristics associated with advanced disease (defined as either a CD4 cell count level of less than 50 cells/mm3 or a WHO Stage 4 condition) at the time of ART initiation and use of stavudine (D4T) or nevirapine (NVP) were identified using a log-link Poisson model with robust standard errors., Results: Among 48,658 patients (69% from Kenya, 22% from Uganda and 9% from Tanzania) accessing ART at 30 clinic sites, the median age at the time of ART initiation was 37 years (IQR: 31-43) and 65% were women. Pre-therapy CD4 counts rose from 87 cells/mm3 (IQR: 26-161) in 2002-03 to 154 cells/mm3 (IQR: 71-233) in 2008-09 (p<0.001). Accessing ART at advanced disease peaked at 35% in 2005-06 and fell to 27% in 2008-09. D4T use in the initial regimen fell from a peak of 88% in 2004-05 to 59% in 2008-09, and a greater extent of decline was observed in Uganda than in Kenya and Tanzania. Self-pay for ART peaked at 18% in 2003, but fell to less than 1% by 2005. In multivariable analyses, accessing ART at advanced immunosuppression was associated with male sex, women without a history of treatment for prevention of mother to child transmission (both as compared with women with such a history) and younger age after adjusting for year of ART initiation and country of residence. Receipt of D4T in the initial regimen was associated with female sex, earlier year of ART initiation, higher WHO stage, and lower CD4 levels at ART initiation and the absence of co-prevalent tuberculosis., Conclusions: Public health ART services in east Africa have improved over time, but the fraction of patients accessing ART with advanced immunosuppression is still high, men consistently access ART with more advanced disease, and D4T continues to be common in most settings. Strategies to facilitate access to ART, overcome barriers among men and reduce D4T use are needed.

Background: Updated World Health Organization guidelines have amplified debate about how resource constraints should impact monitoring strategies for HIV-infected persons on combination antiretroviral therapy (cART). We estimated the incremental benefit and cost effectiveness of alternative monitoring strategies for east Africans with known HIV infection., Methods: Using a validated HIV computer simulation based on resource-limited data (USAID and AMPATH) and circumstances (east Africa), we compared alternative monitoring strategies for HIV-infected persons newly started on cART. We evaluated clinical, immunologic and virologic monitoring strategies, including combinations and conditional logic (e.g., only perform virologic testing if immunologic testing is positive). We calculated incremental cost-effectiveness ratios (ICER) in units of cost per quality-adjusted life year (QALY), using a societal perspective and a lifetime horizon. Costs were measured in 2008 US dollars, and costs and benefits were discounted at 3%. We compared the ICER of monitoring strategies with those of other resource-constrained decisions, in particular earlier cART initiation (at CD4 counts of 350 cells/mm3 rather than 200 cells/mm3)., Results: Monitoring strategies employing routine CD4 testing without virologic testing never maximized health benefits, regardless of budget or societal willingness to pay for additional health benefits. Monitoring strategies employing virologic testing conditional upon particular CD4 results delivered the most benefit at willingness-to-pay levels similar to the cost of earlier cART initiation (approximately $2600/QALY). Monitoring strategies employing routine virologic testing alone only maximized health benefits at willingness-to-pay levels (> $4400/QALY) that greatly exceeded the ICER of earlier cART initiation., Conclusions: CD4 testing alone never maximized health benefits regardless of resource limitations. Programmes routinely performing virologic testing but deferring cART initiation may increase health benefits by reallocating monitoring resources towards earlier cART initiation.

Background: Clinically significant drug-drug interactions (CSDIs) involving antiretrovirals are frequent and under-recognized in developed countries, but data are lacking for developing countries., Methodology and Principal Findings: To investigate the prevalence of CSDIs between antiretrovirals and coadministered drugs, we surveyed prescriptions dispensed in a large HIV clinic in Kenya. Of 1040 consecutive patients screened, 996 were eligible for inclusion. CSDIs were defined as 'major' (capable of causing severe or permanent damage, contraindicated, avoid or not recommended by the manufacturer, or requiring dose modification) or 'moderate' (manufacturers advise caution, or close monitoring, or capable of causing clinical deterioration). A total of 334 patients (33.5%) were at risk for a CSDI, potentially lowering antiretroviral drug concentrations in 120 (12%) patients. Major interactions most frequently involved rifampicin (12.4%, mostly with efavirenz) and azoles (2.7%) whereas moderate interactions were frequently azoles (13%), steroids (11%), and antimalarials (3%). Multivariable analyses suggested that patients at risk for CSDIs had lower CD4 counts (P = 0.006) and baseline weight (P = 0.023) and WHO Stage 3 or 4 disease (P≤0.007). Risk for CSDIs was not associated with particular regimens, although only 116 (11.6%) patients were receiving WHO second line regimens., Conclusions: One in three patients receiving antiretrovirals in our programme were at risk of CSDIs. Strategies need to be urgently developed to avoid important drug interactions, to identify early markers of toxicity and to manage unavoidable interactions safely in order to reduce risk of harm, and to maximize the effectiveness of mass antiretroviral deployment in Africa.

Background: United states Agency for International development-Academic Model for Providing Accesses to Healthcare (USAID-AMPATH) cares for over 80,000 HIV-infected patients. Express care (EC) model addresses challenges of: clinically stable patient's adherent to combined-antiretroviral-therapy with minimal need for clinician intervention and high risk patients newly initiated on cART with CD4 counts < or = 100 cells/mm3 with frequent need for clinician intervention., Objective: To improve patient outcomes without increasing clinic resources., Design: A descriptive study of a clinician supervised shared nurse model., Setting: USAID-AMPATH clinics, Western Kenya., Results: Four thousand eight hundred and twenty four patients were seen during the pilot period, 90.4% were eligible for EC of whom 34.6% were enrolled. Nurses performed all traditional roles and attended to two thirds and three quarters of stable and high risk patient visits respectively. Clinicians attended to one third and one quarter of stable and high risk patient visits respectively and all visits ineligible for express care., Conclusion: The EC model is feasible. Task shifting allowed stable patients to receive visits with nurses, while clinicians had more time to concentrate on patients that were new as well as more acutely ill patients.

Objective: To describe first change or discontinuation in combination antiretroviral treatment (cART) among previously treatment naive, HIV-infected adults in a resource-constrained setting., Methods: The United States Agency for International Development-Academic Model Providing Access to Healthcare Partnership has enrolled >90,000 HIV-infected patients at 18 clinics throughout western Kenya. Patients in this analysis were aged > or =18 years, previously antiretroviral treatment naive, and initiated to cART between January 2006 and November 2007, with at least 1 follow-up visit. A treatment change or discontinuation was defined as change of regimen including single drug substitutions or a complete halting of cART., Results: There were 14,162 patients eligible for analysis and 10,313 person-years of follow-up, of whom 1376 changed or stopped their cART. Among these, 859 (62%) changed their regimen (including 514 patients who had a single drug substitution) and 517 (38%) completely discontinued cART. The overall incidence rate (IR) of cART changes or stops per 100 person-years was 13.3 [95% confidence interval (CI): 12.7-14.1]. The incidence was much higher in the first year of post-cART initiation (IR: 25.0, 95% CI: 23.6-26.3) compared with the second year (IR: 2.4, 95% CI: 2.0-2.8). The most commonly cited reason was toxicity (46%). In multivariate regression, individuals were more likely to discontinue cART if they were World Health Organization stage III/IV [adjusted hazard ratio (AHR): 1.37, 95% CI: 1.11-1.69] or were receiving a zidovudine-containing regimen (AHR: 4.44, 95% CI: 3.35-5.88). Individuals were more likely to change their regimen if they were aged > or =38 years (AHR: 1.44, 95% CI: 1.23-1.69), had to travel more than 1 hour to clinic (AHR: 1.34, 95% CI: 1.15-1.57), had a CD4 at cART initiation < or =111 cells/mm3 (AHR: 1.51, 95% CI: 1.29-1.77), or had been receiving a zidovudine-containing regimen (AHR: 3.73, 95% CI: 2.81-4.95). Those attending urban clinics and those receiving stavudine-containing regimens were less likely to experience either a discontinuation or a change of their cART., Conclusions: These data suggest a moderate incidence of cART changes and discontinuations among this large population of adults in western Kenya. Mostly occurring within 12 months of cART initiation, and primarily due to toxicity, older individuals, those with more advanced disease, and those using zidovudine are at higher risk of experiencing a change or a discontinuation in their cART.

Objective: To determine antiretroviral drug adherence levels of HIV/AIDS in adult patients., Design: A cross sectional study., Setting: Moi Teaching and Referral Hospital (MTRH), Eldoret, Kenya., Subjects: Three hundred and eighty four HIV/AIDS adult patients who attended HIV/AIDS clinic in MTRH for antiretroviral treatment and had been on treatment for at least three months as confirmed by clinicians., Results: Three hundred and eighty four respondents participated in this research; two third of whom were females (68%) and a third were males (32%). Fifty two percent of these had attained secondary or post secondary education. The mean age was 36.1+/-8.5, years and ranged 18-63 years. While 93.5% of the participants adhered to clinic appointments, only 43.2% adhered to taking the drugs as per time schedule., Conclusion: Adherence to time of taking medications was low and could result in reduced efficacy.

Objective: To determine important factors that affect antiretroviral drug adherence among HIV/AIDS male and female adult patients (18 years and above) attending Moi Teaching and Referral Hospital, Eldoret, Kenya., Methods: A cross sectional study involving 384 HIV/AIDS adult patients attending Moi Teaching and Referral Hospital, Eldoret was conducted. These patients were on ARV drugs. They were investigated for factors that affected their drug adherence based on observing the timing of doses and keeping of clinic appointments for drug refills during the months of May, June and July 2005. Data were collected from the respondents using interviewer-administered questionnaires to patients and self-administered questionnaires by ten key informants (nurses and clinicians in charge of HIV/AIDS clinic) selected by purposive sampling. The key variables examined were demographic, other characteristics of the patients and adherence factors. Data were analysed using Statistical Package for Social Sciences (SPSS) version 10.0 for frequencies, cross-tabulations and Chi-Squared test and statistical significance set at p < 0.05., Results: Sixty-eight percent of the respondents on ARVs were females. 52.1% had secondary and post secondary education. They were aged between 18-63 years (mean age 36.1 +/- 8.5 years). Results showed that only 43.2% adhered to the prescribed time of taking drugs. The most commonly cited reasons for missing the prescribed dosing time by the patients were: Being away from home 68.8%, being too busy 58.9%, forgetting 49.0%, having too many medicines to take 32.6% and stigma attached to ARVs 28.9%. There was no significant difference between males and females based on timing of taking medications (chi2 = 2.9412, p = 0.0861). On the basis of keeping clinic appointments, all the respondents claimed to adhere to scheduled clinics. However, from hospital records, it was established that only 93.5% of the respondents kept clinic appointments. The most common reasons for poor adherence to clinic appointments were; Being away from home (50%), forgetting (50%), being too busy (50%), stigma (70%), feeling sick (80%) and changes in work routine (60%)., Conclusion: The key factors affecting adherence were; being away from home, being busy and forgetting. It was recommended that patients should be educated on the importance of strict adherence to the prescribed doses of ARVs as a suitable measure of intervention. Future research should explore multiple-target interventions to resolve the barriers to adherence.

Despite the clear benefits of antiretroviral therapy (ART), only three countries in sub-Saharan Africa have achieved the "3 by 5" goal of treating at least half of the persons living with HIV/AIDS who need it. A major obstacle faced by many lower income countries is the establishment of treatment programs in rural areas where there is a scarcity of trained health care providers and infrastructure. This paper reviews published data on rural ART programs in lower income countries to identify necessary components of such a program. No clearly superior model for rural ART delivery has emerged. All programs document the need for expanded physical infrastructure, laboratory development, recruitment/training of additional health care providers, and/or the introduction of new technologies in order to effectively support the needs of ART roll-out.