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INTRODUCTION: ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second-line protease inhibitor (PI)-based antiretroviral therapy (ART) from 10 low- and middle-income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third-line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV-1 RNA ≤200 copies/ml. We report here long-term outcomes over 144 weeks. METHODS: Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. "Extended Follow-up" of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow-up of ≥144 weeks), with HIV-1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow-up. Proportion of participants with HIV-1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow-up; mean CD4 count changes were estimated using loess regression. RESULTS AND DISCUSSION: Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm3 , and HIV-1 RNA was 4.6 log10 copies/ml. Median follow-up was 168 weeks (IQR: 156-204); 15 (6%) participants were lost to follow-up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV-1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74-85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm3 (95% CI 247-283). CONCLUSIONS: Third-line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second-line PI-based ART prior to the availability of dolutegravir.
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Fármacos Anti-HIV , Infecções por HIV , Inibidores da Protease de HIV , HIV-1 , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Darunavir/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/genética , Humanos , Masculino , Nitrilas , Pirimidinas , RNA/uso terapêutico , Raltegravir Potássico/efeitos adversos , Ritonavir/uso terapêutico , Carga ViralRESUMO
BACKGROUND: Antiretroviral therapy (ART) management is challenging for individuals in resource-limited settings presenting for third-line treatment because of complex resistance patterns, partly due to reduced access to viral load monitoring. We aimed to evaluate use of newer antiretroviral drugs and contemporary management approaches, including population-based sequencing, to select appropriate antiretrovirals, plasma viral load monitoring, and interventions to improve adherence in individuals presenting with second-line viral failure. METHODS: A5288 was a phase 4, third-line ART strategy study done at 19 urban sites in ten countries that enrolled adult participants with confirmed plasma HIV-1 RNA (viral load) of 1000 copies per mL or more after more than 24 weeks of protease inhibitor-based second-line ART. The primary objective was to use antiretrovirals (raltegravir, etravirine, and ritonavir-boosted darunavir) and diagnostic monitoring technologies, including viral load, genotyping, and adherence support to achieve viral load suppression (defined as ≤200 copies per mL) in 65% or more of participants. ART history and real-time drug resistance genotypes were used to assign participants to one of four cohorts: cohort A (no lopinavir resistance) stayed on second-line ART and cohorts B (B1, best available nucleoside reverse transcriptase inhibitors [NRTIs] plus ritonavir-boosted darunavir plus raltegravir; B2, ritonavir-boosted darunavir plus raltegravir plus etravirine; B3, ritonavir-boosted darunavir, raltegravir, and either tenofovir plus emtricitabine or tenofovir plus lamivudine), C (ritonavir-boosted darunavir plus raltegravir plus tenofovir-emtricitabine or tenofovir plus lamivudine), and D (best available NRTIs plus ritonavir-boosted darunavir plus raltegravir) were defined by increasing levels of resistance and received appropriate regimens, including new antiretrovirals. Participants in Cohort B without detectable hepatitis B surface antigen were assigned by blocked randomisation to cohorts B1 and B2, and those with detectable hepatitis B surface antigen were assigned to cohort B3. The trial is registered with ClinicalTrials.gov, number NCT01641367. FINDINGS: From Jan 10, 2013, to Sept 10, 2015, 545 participants were enrolled. 287 (53%) were assigned to cohort A, 74 (14%) to B1, 72 (13%) to B2, eight (1%) to B3, 70 (13%) to C, and 34 (6%) to D. Overall, 349 (64%, 95% CI 60-68) participants achieved viral suppression at week 48, with proportions varying from 125 (44%) of 287 in cohort A to 65 (88%) of 74 in cohort B1, 63 (88%) of 72 in B2, eight (100%) of eight in B3, 63 (90%) of 70 in C, and 25 (74%) of 34 in D. Participants in cohort A remained on their second-line protease inhibitor, and had the most participants with grade 3 or higher adverse events (147 [51%]). INTERPRETATION: Targeted real-time genotyping to select third-line ART can appropriately allocate more costly antiretrovirals to those with greater levels of HIV drug resistance. FUNDING: National Institutes of Health.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Inibidores da Transcriptase Reversa/uso terapêutico , Carga Viral/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Estudos de Coortes , Darunavir/administração & dosagem , Darunavir/efeitos adversos , Países em Desenvolvimento , Farmacorresistência Viral , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Infecções por HIV/sangue , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/efeitos adversos , HIV-1/genética , HIV-1/metabolismo , Humanos , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nitrilas , Estudos Prospectivos , Piridazinas/administração & dosagem , Piridazinas/efeitos adversos , Pirimidinas , Raltegravir Potássico/administração & dosagem , Raltegravir Potássico/efeitos adversos , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Tenofovir/administração & dosagem , Tenofovir/efeitos adversosRESUMO
We assessed prevalence and correlates of bacterial vaginosis (BV) and sexually transmitted infections (STIs) including herpes simplex virus type 2 (HSV-2), gonorrhoea (GC), syphilis (SYP), Chlamydia (CT) and HIV among Kenyan women aged 1834 years who were screened for a contraceptive intravaginal ring study. Women provided demographic, behavioural and medical information, and underwent medical evaluation, including a pelvic exam. We computed crude and adjusted prevalence ratio (aPR) and 95% confidence interval (CI) using log-binomial regression. Of 463 women screened, 457 provided laboratory specimens and were included in the analysis. The median age was 25 years, interquartile range (2128), and 68.5% had completed primary or lower education. Overall, 72.2% tested positive for any STI or BV. Point prevalence was 55.6, 38.5, 3.9, 2.0, 4.6, and 14.7% for HSV-2, BV, GC, SYP, CT, and HIV, respectively. Co-infection with HSV-2, BV, and HIV occurred in 28 (6.1%) participants. Having ≥1 STI/BV was associated with younger age at first sex (≤13 versus 1719 years, aPR=1.27, 95% CI 1.071.51), history of exchange sex (aPR = 2.05, 95% CI 1.073.92), sexual intercourse in the past seven days (aPR = 1.17, 95% CI 1.011.36), and older age (3034 versus 1824 years, aPR = 1.26, 95% CI 1.061.48). STI/BV diagnosis was less likely for women reporting one lifetime sexual partner compared to women with ≥4 lifetime sexual partners (aPR = 0.70, 95% CI 0.540.92). Combination prevention approaches (biomedical, behavioural, social, and structural) tailored to women with diverse risk profiles may help mitigate STI/BV prevalence in this setting.
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Coinfecção/epidemiologia , Anticoncepcionais , Infecções Sexualmente Transmissíveis/epidemiologia , Adolescente , Adulto , Feminino , Gonorreia/epidemiologia , Infecções por HIV/epidemiologia , Herpes Genital/epidemiologia , Humanos , Quênia/epidemiologia , Pessoa de Meia-Idade , Prevalência , Vaginose Bacteriana/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Attention to mental health issues is growing globally. In many countries, including Kenya, however, assessment of psychological distress, especially in rural areas, is limited. METHODS: We analyzed data from young women screened for a longitudinal contraceptive ring study in Kisumu, Kenya. Multivariable regression analysis was used to assess factors associated with recent moderate and high psychological distress, as measured by the Kessler (K-6) psychological distress scale. RESULTS: Among the 461 women screened, most (58.4%) were categorized as having moderate psychological distress, 20.8% were categorized as having low or no psychological distress, and 20.8% were categorized as having high psychological distress. Moderate psychological distress (vs low/no) was significantly more likely among women who reported a history of forced sex and were concerned about recent food insecurity. High (vs low/no) psychological distress was significantly more likely among women who reported a history of forced sex, who were concerned about recent food insecurity, and who self-reported a sexually transmitted infection. CONCLUSION: To reduce psychological distress, a focus on prevention as well as care methods is needed. Girls need a path toward a healthy and productive adulthood with a focus on education, which would help them gain skills to avoid forced sex. Women would benefit from easy access to social services and supports that would help them with basic needs like food security among other things. A holistic or ecological approach to services that would address mental, educational, social, health, and economic issues may have the highest chance of having a long-term positive impact on public health.
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OBJECTIVE: This study sought to measure residual contraceptive hormone levels in vaginal rings as an adherence marker for monitoring product use in clinical trials. STUDY DESIGN: Residual etonogestrel and ethinyl estradiol levels from used NuvaRings® of 26 self-reported adherent women enrolled in a clinical trial of vaginal ring acceptability were compared to those from 16 women who used NuvaRing® as their contraceptive choice. RESULTS: Twenty-one (81%) clinical trial rings had contraceptive hormone levels within the range of those used as a contraceptive choice. Five returned rings had unused or discordant levels of residual contraceptive hormones. CONCLUSION: Residual vaginal ring drug levels could help assess adherence in clinical trials.