Implementation of clinic-based modified-directly observed therapy (m-DOT) for ART; experiences in Mombasa, Kenya.

The effectiveness of modified-directly observed therapy (m-DOT), an adherence support intervention adapted from TB DOTS programmes, has been documented. Describing the implementation process and acceptability of this intervention is important for scaling up, replication in other settings and future research. In a randomised trial in Mombasa, Kenya, patients were assigned to m-DOT or standard of care for 24 weeks. m-DOT entailed twice weekly visits to a health centre for medication collection, ongoing adherence counselling and nurse-observed pill ingestion. Community health workers (CHWs) traced non-attendees, observing pill taking at participant's home. Using process indicators and a semi-structured questionnaire, implementation of m-DOT was evaluated among 94 participants who completed 24 weeks m-DOT (81%; 94/116). Two-thirds of m-DOT recipients were female (64%; 74/116) and a mean 37 years (SD = 7.8). Selection of the m-DOT observation site was determined by proximity to home for 73% (69/94), with the remainder choosing sites near their workplace, or due to perceived high-quality services. A median 42 of 48 scheduled m-DOT visits (IQR = 28-45) were attended. Most found m-DOT is very useful (87%; 82/94) and had positive attitudes to the services. A high proportion received CHWs home visits (96%; 90/94) and looked forward to these. Use of CHWs and several satellite observation sites facilitated provision of services closer to patient's homes. A substantial number, however, thought 24 weeks of m-DOT was too long (43%; 42/94). Our experience suggests that m-DOT services could be implemented widely and are acceptable if delivered with adequate attention to coordination, provision of a broad set of interventions, shifting tasks to less-specialised workers and integration within the health system. m-DOT programmes should utilise existing resources while simultaneously expanding capacity within communities and the public sector. These findings could be used to inform replication of such services and to improve the design of m-DOT in future studies.

Changes in sexual risk taking with antiretroviral treatment: influence of context and gender norms in Mombasa, Kenya.

In-depth interviews were conducted with 23 sexually-active adults receiving antiretroviral treatment (ART) in Mombasa Kenya to understand changes in sexual behaviour after treatment initiation and factors influencing condom use. Advanced HIV disease had previously led to marked decreases in sexual desire and function. After HIV testing, numbers of partners reduced and monogamous relationships began to predominate. Receipt of ART strengthened these changes, while improving sexual health. However, concurrent sexual partnerships continue within polygamous marriage and unprotected sex occurs with regular partners, even those who are HIV-negative. Those who used condoms inconsistently prior to ART often remained inconsistent users thereafter. While disclosure of HIV status appeared to support condom use, this does not always predict protected sex. In addition to classic perceptions about condom's effect on intimacy and trust, traditional gender roles, misconceptions about potential harm from condoms and fertility desires hinder condom use.

Prevalence and predictors of unmet contraceptive need in HIV-positive female sex workers in Mombasa, Kenya.

OBJECTIVES: Female sex workers (FSWs) in sub-Saharan Africa are a key population for HIV prevention and treatment interventions, but less attention is given to their family planning needs. We evaluated the prevalence and predictors of unmet contraceptive need in HIV-positive FSWs. STUDY DESIGN: This cross-sectional analysis used data from an existing longitudinal study of FSWs in Mombasa, Kenya. This analysis included women who were HIV positive, age ≥18 years, pre-menopausal, not currently pregnant or desiring pregnancy, and reported exchanging sex for cash or in-kind payment at the time of enrollment. Unmet contraceptive need was defined as non-use of modern non-barrier contraceptives and not currently trying to become pregnant. Poisson regression was used to identify factors independently associated with unmet contraceptive need. RESULTS: Among 346 HIV-positive FSWs, 125 (36.1%) reported modern non-barrier contraceptive use, leaving 221 (63.9%, 95%CI 58.8-68.9%) with unmet contraceptive need. Condom use was the only form of contraception for 129 (37.3%) participants. In unadjusted analyses, unmet contraceptive need was associated with physical abuse in the past year by someone other than a regular partner (PR 1.2, 95%CI 1.0-1.5), desire for (more) children (PR 1.3, 95%CI 1.1-1.5), and having 2-3 previous pregnancies compared to 0-1 prior pregnancies (PR 0.8, 95%CI 0.6-0.9). In adjusted analyses, lower number of previous pregnancies and having desire for future children remained significantly associated with a higher prevalence of unmet contraceptive need. CONCLUSIONS: Unmet need for modern non-barrier contraception was found in two-thirds of HIV-positive FSWs who reported that they were not currently trying to become pregnant, and was higher in women with the lowest number of prior pregnancies (0-1 prior pregnancies) and in those reporting desire for (more) children in the future. These findings highlight the need for concerted efforts to identify and eliminate barriers to contraceptive use in FSWs living with HIV.

Evaluation of the association between the concentrations of key vaginal bacteria and the increased risk of HIV acquisition in African women from five cohorts: a nested case-control study.

BACKGROUND: Disruptions of vaginal microbiota might increase women's susceptibility to HIV infection. Advances in molecular microbiology have enabled detailed examination of associations between vaginal bacteria and HIV acquisition. Therefore, this study aimed to evaluate the association between the concentrations of specific vaginal bacteria and increased risk of HIV acquisition in African women. METHODS: We did a nested case-control study of participants from eastern and southern Africa. Data from five cohorts of African women (female sex workers, pregnant and post-partum women, and women in serodiscordant relationships) were used to form a nested case-control analysis between women who acquired HIV infection versus those who remained seronegative. Deep sequence analysis of broad-range 16S rRNA gene PCR products was applied to a subset of 55 cases and 55 controls. From these data, 20 taxa were selected for bacterium-specific real-time PCR assays, which were examined in the full cohort as a four-category exposure (undetectable, first tertile, second tertile, and third tertile of concentrations). Conditional logistic regression was used to generate odds ratios (ORs) and 95% CIs. Regression models were stratified by cohort, and adjusted ORs (aORs) were generated from a multivariable model controlling for confounding variables. The Shannon Diversity Index was used to measure bacterial diversity. The primary analyses were the associations between bacterial concentrations and risk of HIV acquisition. FINDINGS: Between November, 2004, and August, 2014, we identified 87 women who acquired HIV infection (cases) and 262 controls who did not acquire HIV infection. Vaginal bacterial community diversity was higher in women who acquired HIV infection (median 1·3, IQR 0·4-2·3) than in seronegative controls (0·7, 0·1-1·5; p=0·03). Seven of the 20 taxa showed significant concentration-dependent associations with increased odds of HIV acquisition: Parvimonas species type 1 (first tertile aOR 1·67, 95% CI 0·61-4·57; second tertile 3·01, 1·13-7·99; third tertile 4·64, 1·73-12·46; p=0·005) and type 2 (first tertile 3·52, 1·63-7·61; second tertile 0·85, 0·36-2·02; third tertile 2·18, 1·01-4·72; p=0·004), Gemella asaccharolytica (first tertile 2·09, 1·01-4·36; second tertile 2·02, 0·98-4·17; third tertile 3·03, 1·46-6·30; p=0·010), Mycoplasma hominis (first tertile 1·46, 0·69-3·11; second tertile 1·40, 0·66-2·98; third tertile 2·76, 1·36-5·63; p=0·048), Leptotrichia/Sneathia (first tertile 2·04, 1·02-4·10; second tertile 1·45, 0·70-3·00; third tertile 2·59, 1·26-5·34; p=0·046), Eggerthella species type 1 (first tertile 1·79, 0·88-3·64; second tertile 2·62, 1·31-5·22; third tertile 1·53, 0·72-3·28; p=0·041), and vaginal Megasphaera species (first tertile 3·15, 1·45-6·81; second tertile 1·43, 0·65-3·14; third tertile 1·32, 0·57-3·05; p=0·038). INTERPRETATION: Differences in the vaginal microbial diversity and concentrations of key bacteria were associated with greater risk of HIV acquisition in women. Defining vaginal bacterial taxa associated with HIV risk could point to mechanisms that influence HIV susceptibility and provide important targets for future prevention research. FUNDING: National Institute of Child Health and Human Development.

Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding.

BACKGROUND: Antiretroviral therapy (ART) may decrease HIV-1 infectivity in women by reducing genital HIV-1 shedding. OBJECTIVES: To evaluate the time course and magnitude of decay in cervical and vaginal HIV-1 shedding as women initiate ART. METHODS: This prospective, observational study of 20 antiretroviral-naive women initiating ART with stavudine, lamivudine, and nevirapine measured HIV-1 RNA in plasma, cervical secretions, and vaginal secretions. Qualitative polymerase chain reaction estimated HIV-1 DNA in cervical and vaginal samples. Perelson's two-phase viral decay model and non-linear random effects were used to compare RNA decay rates. Decreases in proviral DNA were evaluated using logistic regression and generalized estimating equations. RESULTS: Significant decreases in the quantity of HIV-1 RNA were observed by day 2 in plasma (P < 0.001), day 2 in cervical secretions (P = 0.001), and day 4 in vaginal secretions (P < 0.001). Modeled initial and subsequent RNA decay rates in plasma, cervical secretions, and vaginal secretions were 0.6, 0.8, and 1.2 log10 virions/day, and 0.04, 0.05, and 0.06 log10 virions/day, respectively. The initial decay rate for vaginal HIV-1 RNA was more rapid than for plasma RNA (P = 0.02). Detection of HIV-1 DNA decreased significantly in vaginal secretions during the first week (P < 0.001). At day 28, 10 women had detectable HIV-1 RNA or proviral DNA in genital secretions. CONCLUSIONS: Genital HIV-1 shedding decreased rapidly after ART initiation, consistent with a rapid decrease in infectivity. However, incomplete viral suppression in half of these women may indicate an ongoing risk of transmission.

Human herpesvirus 8 seroconversion in Kenyan women by enzyme-linked immunosorbent assay and immunofluorescence assay.

BACKGROUND: Human herpesvirus 8 (HHV-8) antibody tests vary in reported sensitivity and specificity, depending on the population tested and the assay. OBJECTIVE: The purpose of this study was to compare the ability to detect seroconversion to HHV-8 in a cohort of HHV-8 seronegative female commercial sex workers in Kenya using three tests: HHV-8 viral lysate-based enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay for HHV-8 lytic antigens (IFA-lytic) and IFA for latent nuclear antigens (IFA-LANA). STUDY DESIGN: By ELISA, 16 women from a prospective cohort of commercial sex workers were identified as seroconverting to HHV-8. A total of 124 post-enrollment samples from these 16 women as well as the enrollment samples were tested for HHV-8 antibodies by all three assays to monitor seroconversion. RESULTS: Of 16 women with apparent seroconversion by ELISA, 8 had a rise in IFA-lytic titers either concomitant with or prior to the first positive ELISA sample and no initial LANA by IFA. Five of the 16 women were IFA-LANA positive at entry, indicating prior infection with HHV-8. Three women had no evidence of seroconversion by either IFA-lytic or IFA-LANA and two of these three had increased ELISA reactivity concomitant with HIV-1 infection. CONCLUSIONS: Conversion from a negative to a positive ELISA result for HHV-8 antibody indicated seroconversion in only half of the study cohort of 16 women when IFA-lytic and IFA-LANA results were considered. The IFA-lytic assay was more sensitive than ELISA for early antibody responses. The IFA-LANA was positive in some women who had neither IFA-lytic nor ELISA antibodies suggesting it may be a marker for latent infections. Presumptive identification of incident HHV-8 infection by ELISA screening followed by IFA-lytic testing to confirm the positive test and IFA-LANA to rule out prior infection provides the most accurate documentation of HHV-8 seroconversion.

Prevalence, clinical and virologic outcomes of hepatitis B virus co-infection in HIV-1 positive Kenyan women on antiretroviral therapy.

BACKGROUND: Sub-Saharan Africa carries a high burden of co-infection with HIV-1 and hepatitis B virus (HBV). In this region, individuals with HIV-1/HBV co-infection on antiretroviral therapy (ART) frequently receive lamivudine as the only agent active against HBV, raising concerns for development of HBV resistance to lamivudine. We aimed to determine the prevalence, clinical, and virologic outcomes of chronic HBV infection, including HBV resistance to lamivudine, in a cohort of HIV-1 seropositive Kenyan women on long-term ART. METHODS: In this prospective cohort study, HIV-1 seropositive women initiated three-drug ART regimens that included lamivudine as the single drug active against HBV. Archived samples were tested for HBsAg, with further testing to determine HBeAg seroprevalence, HBV DNA suppression, and lamivudine resistance. We estimated the prevalence of chronic HBV and examined associations between HBV co-infection and clinical and virologic outcomes with chi-square tests, logistic regression, Kaplan-Meier and Cox regression. RESULTS: In a cohort of 159 women followed for a median of 3.4 years (interquartile range 1.4-4.5), 11 (6.9%; 95% CI 3.1-10.7) had chronic HBV infection. Of these, 9 (82%) achieved undetectable plasma HBV DNA levels. One woman developed lamivudine resistance, for an incidence of 3 per 100 person-years. The HBV co-infected women were at greater risk for abnormal ALT elevations compared to HIV-1 mono-infected women (HR 2.37; 95% CI 1.1-5.3). There were no differences between HBV-infected and uninfected women in mortality, CD4 count, or HIV-1 RNA suppression. CONCLUSION: The prevalence of chronic HBV in this cohort was similar to recent studies from other African populations. Given our long-term follow-up, lamivudine resistance was lower than expected for HIV-1/HBV co-infected patients. Improved screening for HBV and extended follow-up of HIV-1/HBV co-infected individuals are needed to better understand the impact of different ART regimens on clinical outcomes in this population.

Treatment with antiretroviral therapy is not associated with increased sexual risk behavior in Kenyan female sex workers.

OBJECTIVE: The objective of this study was to test the hypothesis that sexual risk behavior would increase following initiation of antiretroviral therapy (ART) in Kenyan female sex workers (FSWs). DESIGN: Prospective cohort study. SETTING: FSW cohort in Mombasa, Kenya, 1993-2008. SUBJECTS: Eight hundred and ninety-eight women contributed HIV-1-seropositive follow-up visits, of whom 129 initiated ART. INTERVENTION: Beginning in March 2004, ART was provided to women qualifying for treatment according to Kenyan National Guidelines. Participants received sexual risk reduction education and free condoms at every visit. MAIN OUTCOME MEASURES: Main outcome measures included unprotected intercourse, abstinence, 100% condom use, number of sexual partners, and frequency of sex. Outcomes were evaluated at monthly follow-up visits using a 1-week recall interval. RESULTS: Compared with non-ART-exposed follow-up, visits following ART initiation were not associated with an increase in unprotected sex [adjusted odds ratio (AOR) 0.86, 95% confidence interval (CI) 0.62-1.19, P = 0.4]. There was a nonsignificant decrease in abstinence (AOR 0.81, 95% CI 0.65-1.01, P = 0.07), which was offset by a substantial increase in 100% condom use (AOR 1.54, 95% CI 1.07-2.20, P = 0.02). Numbers of sex partners and frequency of sex were similar before versus after starting ART. A trend for decreased sexually transmitted infections following ART initiation provides additional support for the validity of the self-reported behavioral outcomes (AOR 0.67, 95% CI 0.44-1.02, P = 0.06). CONCLUSION: In the setting of ongoing risk reduction education and provision of free condoms, initiation of ART was not associated with increased sexual risk behavior in this cohort of Kenyan FSWs.

Safer sexual behaviors after 12 months of antiretroviral treatment in Mombasa, Kenya: a prospective cohort.

Roll-out of antiretroviral treatment (ART) raises concerns about the potential for unprotected sex if sexual activity increases with well-being, resulting in continued HIV spread. Beliefs about reduced risk for HIV transmission with ART may also influence behavior. From September 2003 to November 2004, 234 adults enrolled in a trial assessing the efficacy of modified directly observed therapy in improving adherence to ART. Unsafe sexual behavior (unprotected sex with an HIV-negative or unknown status partner) before starting ART and 12 months thereafter was compared. Participants were a mean 37.2 years (standard deviation [SD] = 7.9 years) and 64% (149/234) were female. Nearly half (107/225) were sexually active in the 12 months prior to ART, the majority (96/107) reporting one sexual partner. Unsafe sex was reported by half of those sexually active in the 12 months before ART (54/107), while after 12 months ART, this reduced to 28% (30/107). Unsafe sex was associated with nondisclosure of HIV status to partner; recent HIV diagnosis; not being married or cohabiting; stigma; depression and body mass index <18.5 kg/m(2). ART beliefs, adherence, and viral suppression were not associated with unsafe sex. After adjusting for gender and stigma, unsafe sex was 0.59 times less likely after 12 months ART than before initiation (95% confidence interval [CI] = 0.37-0.94; p = 0.026). In conclusion, although risky sexual behaviors had decreased, a considerable portion do not practice safe sex. Beliefs about ART's effect on transmission, viral load, and adherence appear not to influence sexual behavior but require long-term surveillance. Positive prevention interventions for those receiving ART must reinforce safer sex practices and partner disclosure.

Short- and long-term efficacy of modified directly observed antiretroviral treatment in Mombasa, Kenya: a randomized trial.

OBJECTIVES: To determine short- and long-term efficacy of modified directly observed therapy (m-DOT) on antiretroviral adherence. DESIGN: Randomized controlled trial. SETTING AND ANALYTIC APPROACH: From September 2003 to November 2004, 234 HIV-infected adults were assigned m-DOT (24 weeks of twice weekly health center visits for nurse-observed pill ingestion, adherence support, and medication collection) or standard care. Follow-up continued until week 72. Self-reported and pill-count adherence and, secondarily, viral suppression and body mass index measures are reported. Generalized estimating equations adjusted for intraclient clustering and covariates were used. RESULTS: During weeks 1-24, 9.1% (9/99) of m-DOT participants reported missing doses compared with 19.1% (20/105) of controls (P = 0.04) and 96.5% (517/571) of m-DOT pill-count measures were >or=95% compared with 86.1% (445/517) in controls [adjusted odds ratio = 4.4; 95% confidence interval (CI) = 2.6 to 7.5; P < 0.001. Adherence with m-DOT was 4.8 times greater (95% CI = 2.7 to 8.6; P < 0.001) with adjustment for depression and HIV-related hospitalization. In weeks 25-48, adherence with m-DOT (488/589) was similar to controls (507/630). Viral suppression at 48 weeks was 2.0 times (95% CI = 0.8 to 5.2; P = 0.13) as likely in m-DOT participants as controls. M-DOT patients had larger body mass index increases at 24 weeks (2.2 vs 1.4 kg/m3; P = 0.014). Viral suppression was more likely at week 48 (21/25 vs 13/22; P = 0.057) and week 72 (27/30 vs 15/23; P = 0.027) among depressed participants receiving m-DOT. CONCLUSIONS: M-DOT increased adherence, most notably among depressed participants.

Opportunity for prevention of HIV and sexually transmitted infections in Kenyan youth: results of a population-based survey.

BACKGROUND: Data from sentinel serosurveillance are useful to estimate HIV infection in populations but may not be representative of the general population. General population-based surveys attempt to avoid selection bias and are the most appropriate for tracking changes in exposure to risk of HIV infection over time and assessing changes in behavior following prevention campaigns. OBJECTIVES: To provide baseline data for targeted sexually transmitted infection (STI) and HIV infection prevention interventions by studying parameters of sexual behavior and knowledge of HIV infection and STIs, measuring health-seeking behavior related to STIs, and measuring gonorrhea, Chlamydia, syphilis, and HIV-1 prevalences. DESIGN: Population-based survey with stratified sampling by age group from randomly selected households in a suburb of Mombasa, Kenya. METHODS: A standard questionnaire was administered to 1497 consenting adults between the ages of 15 and 49 years who lived in randomly selected households. Urine and blood samples were obtained for the estimation of gonorrhea, chlamydial infection, syphilis, and HIV-1 infection prevalences. RESULTS: Sexual activity in the past 12 months was limited to one partner in all age groups for most sexually active men (68%) and women (88%). More men than women reported two or more partners in the past 12 months (23% vs. 5%, respectively). Almost one half of those persons in the 15- to 19-year-old age group (56% of boys and 48% of girls) were sexually active. Condom use was low with all sexual partners, more so for women than for men. Reported STI symptoms in the past 12 months were high for both men and women. Knowledge of STI symptoms and HIV infection was present but incomplete. Overall HIV seroprevalence was 10.8%, with significantly higher rates among women (13.7%) than among men (8.0%). HIV seroprevalence in the 15- to 19-year-old age group was 3.2%. Female gender, Protestant religion, Catholic religion, and being divorced, separated, and widowed were significantly associated with HIV seroprevalence. Prevalences of gonorrhea, chlamydial infection, and syphilis were 0.9%, 1.5%, and 1.3%, respectively. CONCLUSIONS: This study emphasizes the vulnerability of young adults, in particular young women, to HIV infection and the need for intensive interventions in this group. The low use of condoms, incomplete knowledge of HIV infection and STIs, the high number of reported STIs, and the relatively low HIV-1 seroprevalence among the 15- to 19-year-old group indicate a large need for intensive STI and HIV infection prevention programs, especially for the 15- to 19-year-old age group.