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Background. The objective of the present study was to assess whether the high-density lipoprotein cholesterol (HDL-c)-increasing effect of nevirapine (NVP), as observed in human immunodeficiency virus type 1 (HIV-1)-infected subjects, at least in part may relate to intrinsic properties of NVP.Methods. At 2, 6, and 12 weeks after birth, complete lipid profiles as well as plasma apolipoproteins levels were assessed in 80 HIV-uninfected newborns, half of whom received NVP and half lamivudine (3TC), respectively. Newborns were randomly selected from a randomized trial in which NVP or 3TC had been administered to HIV-uninfected infants born to HIV-infected mothers to try and prevent HIV-1 transmission from occurring during breast-feeding.Results. After 6 weeks of therapy, the expected physiological decline in HDL-c levels in the newborns was attenuated in infants treated with NVP, compared with levels in those treated with 3TC. Apolipoprotein A-I (apoA-I) levels were higher at all time points in the NVP arm than they were in the 3TC arm (P=.02), reaching peak levels at 6 weeks. The difference in HDL-c was no longer significant at 12 weeks.Conclusions. apoA-I levels and HDL-c were elevated in HIV-1-uninfected newborns receiving NVP, compared with those receiving 3TC. These data support that NVP may indeed have intrinsic apoA-I and HDL-c elevating properties in humans. Copyright © 2007 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

In Uganda, the HIV Network for Prevention Trials (HIVNET) 012 study recently demonstrated that single-dose nevirapine (Nvp) prophylaxis is effective for preventing mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1). This exploratory study examines the relationship between HIV-1 subtype, MTCT, and the development of Nvp resistance (Nvp(R)) in women enrolled in HIVNET 012. For 102 women (32 whose infants were HIV-1 infected by age 6-8 weeks and 70 whose infants were uninfected), HIV-1 subtypes included 50 (49%) subtype A, 35 (34%) subtype D, 4 (4%) subtype C, 12 (12%) recombinant subtype, and 1 unclassified. There was no apparent difference in the rate of MTCT among women with subtype A versus D (adjusted odds ratio [OR], 1.24; 95% confidence interval [CI], 0.45-3.43). Nvp(R) mutations were detected more frequently at 6-8 weeks postpartum in women with subtype D than in women with subtype A (adjusted OR, 4.94; 95% CI, 1.21-20.22). Additional studies are needed to further define the relationship between HIV-1 subtype and Nvp(R) among women receiving Nvp prophylaxis. © 2001 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Abstract Background Cervical cancer is the commonest cancer of women in Uganda. Over 80% of women diagnosed in Mulago national referral and teaching hospital, the biggest hospital in Uganda, have advanced disease. Pap smear screening, on opportunistic rather than systematic basis, is offered free in the gynaecological outpatients clinic and the postnatal/family planning clinics. Medical students in the third and final clerkships are expected to learn the techniques of screening. Objectives of this study were to describe knowledge on cervical cancer, attitudes and practices towards cervical cancer screening among the medical workers of Mulago hospital. Methods In a descriptive cross-sectional study, a weighted sample of 310 medical workers including nurses, doctors and final year medical students were interviewed using a self-administered questionnaire. We measured knowledge about cervical cancer: (risk factors, eligibility for screening and screening techniques), attitudes towards cervical cancer screening and practices regarding screening. Results Response rate was 92% (285). Of these, 93% considered cancer of the cervix a public health problem and knowledge about Pap smear was 83% among respondents. Less than 40% knew risk factors for cervical cancer, eligibility for and screening interval. Of the female respondents, 65% didn't feel susceptible to cervical cancer and 81% had never been screened. Of the male respondents, only 26% had partners who had ever been screened. Only 14% of the final year medical students felt skilled enough to use a vaginal speculum and 87% had never performed a pap smear. Conclusion Despite knowledge of the gravity of cervical cancer and prevention by screening using a Pap smear, attitudes and practices towards screening were negative. The medical workers who should be responsible for opportunistic screening of women they care for are not keen on getting screened themselves. There is need to explain/understand the cause of these attitudes and practices and identify possible interventions to change them. Medical students leave medical school without adequate skills to be able to effectively screen women for cervical cancer wherever they go to practice. Medical students and nurses training curricula needs review to incorporate practical skills on cervical cancer screening.

OBJECTIVE: We investigated whether vitamin A supplementation would decrease mortality and morbidity rates in children infected with the human immunodeficiency virus (HIV). METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial at Mulago Hospital, a large hospital that serves the urban and semiurban populations of Kampala, Uganda. One hundred eighty-one HIV-infected children were enrolled at 6 mo and randomized to receive vitamin A supplementation, 60 mg retinol equivalent, or placebo every 3 mo from ages 15 to 36 mo. Morbidity was assessed through a 7-d morbidity history every 3 mo, and vital events were measured. Children received daily trimethoprim-sulfamethoxazole prophylactic therapy. RESULTS: After age 15 mo, children were followed for a median of 17.8 mo (interquartile range = 11.1 to 21.0 mo). The trial was stopped when there was a new policy to implement a program of mass supplementation of vitamin A in the country. Mortality rates among 87 children in the vitamin A group and 94 children in the control group were 20.6% and 32.9%, respectively, yielding a relative risk of 0.54 (95% confidence interval, 0.30 to 0.98; P = 0.044) after adjusting for baseline weight-for-height Z score. Children who received vitamin A had lower modified point prevalences of persistent cough (odds ratio, 0.47; 95% confidence interval, 0.23 to 0.96; P = 0.038) and chronic diarrhea (odds ratio, 0.48; 95% confidence interval, 0.19 to 1.18; P = 0.11) and a shorter duration of ear discharge (P = 0.03). Vitamin A supplementation had no significant effect on modified point prevalences of fever, ear discharge, bloody stools, or hospitalizations. CONCLUSIONS: Vitamin A supplementation decreases mortality rate in HIV-infected children and should be considered in the care for these children in developing countries. [ABSTRACT FROM AUTHOR]

Objectives: To describe 5-year growth, survival, and long-term safety among children exposed to nevirapine or zidovudine in an African perinatal prevention trial, HIVNET 012., Methods: All study children who were alive at the age 18 months were eligible for an extended follow-up study. Children whose families consented were enrolled and evaluated every 6 months from 24 to 60 months. At each visit, history, physical examination, and growth measures were taken. From these measurements, Z scores based on World Health Organization (WHO) standards were computed. Serious adverse event data were collected. Data from the initial and extended follow-up cohorts were included in the analysis., Results: Five hundred twenty-eight study children were alive at the age 18 months, and 491 (426 HIV uninfected and 65 infected) were enrolled into the follow-up study. Both exposed but uninfected children and HIV-infected children were substantially below WHO growth standards for weight and height. Head circumference Z scores for uninfected children were comparable with WHO norms. Five-year survival rates were 93% for uninfected children versus 43% for infected children. Long-term safety and growth outcomes in the 2 study arms were similar., Conclusions: Both infected and uninfected children in the 5-year HIVNET 012 follow-up showed poor height and weight growth outcomes, underscoring the need for early nutritional interventions to improve long-term growth of all infants born to HIV-infected women in resource-limited settings. Similarly, the low 5-year survival among HIV-infected children support the importance of early initiation of antiretroviral therapy. Both peripartum nevirapine and zidovudine were safe.

Background: This phase III, randomized, clinical trial compared single-dose nevirapine (sdNVP) plus HIV hyperimmune globulin (HIVIGLOB) with sdNVP alone for preventing maternal-to-child transmission of HIV. Primary objectives were to determine rates of HIV infection among infants and to assess the safety of HIVIGLOB in combination with sdNVP in HIV-infected Ugandan pregnant women and their infants., Methods: Mother-infant pairs were randomized to receive 200 mg of nevirapine to women in labor and 2 mg/kg NVP to newborns within 72 hours after birth (sdNVP arm) or to receive sdNVP plus a single intravenous 240-mL dose of HIVIGLOB given to women at 36- to 38-week gestation and a single intravenous 24-mL dose to newborns within 18 hours of birth (HIVIGLOB/sdNVP arm). Risk of HIV infection was determined using Kaplan-Meier and risk ratio estimates at birth, 2, 6, 14 weeks, 6, and 12 months of age., Results: Intent-to-treat analysis included 198 HIVIGLOB/sdNVP and 294 sdNVP mother-infant pairs. At 6 months of age, the primary endpoint, there was no statistically significant difference in HIV transmission in the HIVIGLOB/sdNVP arm vs. the sdNVP arm [18.7% vs. 15.0%; risk ratio = 1.240 (95% confidence interval: 0.833 to 1.846); P = 0.290]. Similarly, the proportion of serious adverse events in the HIVIGLOB/sdNVP and sdNVP arms, respectively, for mothers (18.9% vs. 19.3%; P = 0.91) and infants (62.6% vs. 59.5%; P = 0.51) was not significantly different., Conclusions: Giving mother-infant pairs an infusion of peripartum HIV hyperimmune globulin in addition to sdNVP for preventing maternal-to-child transmission was as safe as sdNVP alone but was no more effective than sdNVP alone in preventing HIV transmission.

Screening for HPV-driven cervical dysplasia and neoplasia is a significant public health concern in the developing world. The purpose of this study was to use a manual, low-cost liquid-based Pap preparation to determine HPV prevalence in HIV-positive and HIV-negative young women in Kampala, Uganda and to correlate cervical cytopathology with HPV-DNA genotype. About 196 post-partum women aged 18-30 years underwent rapid HIV testing and pelvic examination. Liquid-based cervical cytology samples were processed using a low-cost manual technique. A DNA collection device was used to collect specimens for HPV genotyping. HIV and HPV prevalence was 18 and 64%, respectively. Overall, 49% of women were infected with a high-risk HPV genotype. The most common high-risk HPV genotypes were 16 (8.2%), 33 (7.7%), 35 (6.6%), 45 (5.1%), and 58 (5.1%). The prevalence of HPV 18 was 3.6%. HIV-positive women had an HPV prevalence of 86% compared to 59% in HIV-negative women (P = 0.003). The prevalence of HPV 16/18 did not differ by HIV status. HIV-positive women were infected with a significantly greater number of HPV genotypes compared to HIV-negative women. By multivariate analysis, the main risk factor for HPV infection was coinfection with HIV. HIV-positive women were four times more likely to have abnormal cytology than HIV-negative women (43% vs. 11.6%, P < 0.001). These data highlight that HIV infection is a strong risk factor for HPV infection and resultant abnormal cervical cytology. Notably, the manual low-cost liquid-based Pap preparation is practical in this setting and offers an alternate method for local studies of HPV vaccine efficacy., (2009 Wiley-Liss, Inc.)

Objective: To assess serious gastroenteritis risk and mortality associated with early cessation of breastfeeding in infants enrolled in 2 prevention of maternal-to-child HIV-transmission trials in Uganda.Methods: We used hazard rates to evaluate serious gastroenteritis events by month of age and mortality among HIV-exposed uninfected infants enrolled in the HIV Network for Prevention Trials (HIVNET 012) (1997–2001) and HIV hyperimmune globulin (HIVIGLOB)/nevirapine (NVP) (2004–2007) trials. HIV-infected mothers were counseled using local infant feeding guidelines current at the time.Results: Breastfeeding cessation occurred earlier in HIVIGLOB/NVP compared with HIVNET 012 (median 4.0 versus 9.3 months,P,0.001). Rates of serious gastroenteritis were higher in HIVIGLOB/NVP (8.0/1000 child-months) than in HIVNET 012 (3.1/1000 child-months; P , 0.001). Serious gastroenteritis events also peaked earlier at 3–4 and 7–8 months (16.2/1000 and 15.0/1000 child-months,respectively) compared with HIVNET 012 at 9–10 months (20.8/1000 child-months). All cause infant mortality did not statistically differ between the HIVIGLOB/NVP and the HIVNET 012 trials [3.2/1000 versus 2.0/1000 child-months, respectively (P = 0.10)].Conclusions: Early breastfeeding cessation seen in the HIVIGLOB/NVP trial was associated with increased risk of serious gastroenteritis among HIV-exposed uninfected infants when compared with later breastfeeding cessation in the HIVNET 012 trial.Testing interventions, which could decrease HIV transmission through breastfeeding and allow safe

Background: HIV-1 mother-to-child transmission (MTCT) remains an important route of infection in sub-Saharan Africa., Methods: Genetic variants in CCR5 promoter, CCR2, CX3CR1, and Stromal cell-derived factor-1 (SDF-1) genes were determined in 980 infants from sub-Saharan Africa using real-time polymerase chain reaction to determine association with MTCT., Results: In antiretroviral-naive mother-infant pairs (n = 637), CCR5 promoter polymorphisms at positions 59029: A allele vs. G/G [odds ratio (OR): 1.61, 95% confidence interval (CI): 1.04 to 2.48; P = 0.032] and 59356: T allele vs. C/C (OR: 0.63, 95% CI: 0.41 to 0.96; P = 0.033) and CCR2-180: G allele vs. A/A (OR: 3.32, 95% CI: 1.13 to 9.73; P = 0.029) were associated with risk of MTCT. Treatment of HIV-1-infected mothers and infants with single-dose nevirapine or perinatal zidovudine altered but did not eliminate the association of genetic variants with MTCT., Conclusions: CCR5 promoter, CCR2, and CX3CR1 polymorphisms were associated with risk of MTCT likely through their role as an HIV-1 coreceptor or by modulating the early immune response. Host genetics may continue to alter MTCT when short-course interventions that only partially suppress virus are used. These findings will need to be confirmed in validation cohorts with a large number of infected infants.

Background: Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SD NVP alone for prevention of vertical transmission of human immunodeficiency virus (HIV) through breastfeeding. We analyzed NVP resistance in HIV-infected Ugandan infants who received either SD NVP or extended NVP prophylaxis., Methods: We tested plasma HIV by using a genotyping assay (ViroSeq; Celera Diagnostics), a phenotypic resistance assay (PhenoSense; Monogram Biosciences), and sensitive point mutation assay (LigAmp, for K103N, Y181C, and G190A)., Results: When infants were 6 weeks old, ViroSeq detected NVP resistance in a higher proportion of infants in the extended NVP arm than in the SD NVP arm (21 of 25 [84%] vs. 12 of 24 [50%]; P = .01). Similar results were obtained with LigAmp and PhenoSense. In both study arms, infants who were HIV infected at birth frequently had NVP resistance detected. In contrast, infants in the extended NVP arm who were HIV infected after birth were more likely to have resistance detected at 6 weeks, compared with infants in the SD NVP arm. The use of extended NVP prophylaxis was also associated with detection of NVP resistance by ViroSeq at 6 months (7 of 7 [100%] infants in the extended NVP arm had resistance detected, compared with 1 of 6 [16.7%] infants in the SD NVP arm; P = .005)., Conclusions: The use of extended NVP prophylaxis was associated with increased selection for and persistence of NVP resistance in HIV-infected Ugandan infants.

Background: Progestin-only injectable contraceptives continue to gain in popularity, but uncertainty remains about pregnancy risk among women late for reinjection. The World Health Organization (WHO) recommends a "grace period" of 2 weeks after the scheduled 13-week reinjection. Beyond 2 weeks, however, many providers send late clients home to await menses., Study Design: A prospective cohort study in Uganda, Zimbabwe and Thailand followed users of depot-medroxyprogesterone acetate (DMPA) for up to 24 months. Users were tested for pregnancy at every reinjection, allowing analysis of pregnancy risk among late comers., Results: The analysis consists of 2290 participants contributing 13,608 DMPA intervals. The pregnancy risks per 100 women-years for "on time" [0.6; 95% confidence interval (CI), 0.33-0.92], "2-week grace" (0.0; 95% CI, 0.0-1.88) and "4-week grace" (0.4; 95% CI, 0.01-2.29) injections were low and virtually identical., Conclusion: Extending the current WHO grace period for DMPA reinjection from 2 to 4 weeks does not increase pregnancy risk and could increase contraceptive continuation.

Background: Human immunodeficiency virus type 1 (HIV-1) may utilize the CXCR4 coreceptor (X4 virus), the CCR5 coreceptor (R5 virus), or both (dual/mixed [DM] virus). We analyzed HIV-1 coreceptor tropism in Ugandan infants enrolled in the HIVNET (HIV Network for Prevention Trials) 012 trial., Methods: Plasma or serum was analyzed using a commercial coreceptor tropism assay. HIV env subtype was determined by phylogenetic methods., Results: Tropism results were obtained for 57 samples from infants collected 6-14 weeks after birth. Fifty-two infants had only R5 virus, and 5 had either X4 or DM virus. The mothers of those 5 infants also had X4 or DM virus. In infants, subtype D infection was associated with high-level infectivity in CCR5-bearing cells and also with the detection of X4 or DM strains. High-level infectivity in CCR5-bearing cells was associated with decreased infant survival, but infection with X4 or DM virus was not. HIV clones from infants with DM viral populations showed different patterns of coreceptor use. V3 loop sequence-based algorithms predicted the tropism of some, but not all, env clones., Conclusions: Complex patterns of HIV tropism were found in HIV-infected newborn infants. Subtype D infection was associated with X4 virus and with high-level replication in CCR5-bearing cells. High-level replication of R5 virus was associated with decreased infant survival.

Background: Trichomoniasis vaginalis is the most common nonviral sexually transmitted infection (STI) worldwide, with a particularly high prevalence in regions of human immunodeficiency virus (HIV) endemicity. However, its impact as a cofactor for HIV acquisition is poorly understood., Methods: Samples from 213 women who experienced HIV seroconversion (cases) during a longitudinal study involving 4450 women in Uganda and Zimbabwe were matched with samples from HIV-uninfected women (controls). All samples underwent polymerase chain reaction (PCR) analysis for Trichomonas vaginalis DNA. For cases, analyzed samples were from the visit in which HIV seroconversion was detected and the visit preceding detection of seroconversion; for controls, one analyzed sample was from the visit matched by follow-up duration to the cases' seroconversion visit, and the other sample was from the visit immediately preceding the matched visit., Results: The prevalence of T. vaginalis infection before HIV infection was 11.3% in cases and 4.5% in controls (P = .002). In multivariable analysis controlling for hormonal contraception, other STIs, behavioral, and demographic factors, the adjusted odds ratio for HIV acquisition was 2.74 (95% confidence interval, 1.25-6.00) for T. vaginalis-positive cases. The presence of behavioral risk factors for HIV infection, study recruitment from a referral population at high-risk for HIV, primary sex partner-associated risk for HIV infection, and herpes simplex virus type 2 seropositivity were also predictive of incident HIV infection., Conclusions: T. vaginalis infection is strongly associated with an increased risk for HIV infection in this general population of African women. Given the high prevalence of T. vaginalis infection in HIV-endemic areas, T. vaginalis control may have a substantial impact on preventing HIV acquisition among women.

Objective: To determine costs for adverse event (AE) procedures for a large HIV perinatal trial by analyzing actual resource consumption using activity-based costing (ABC) in an international research setting., Methods: The AE system for an ongoing clinical trial in Uganda was evaluated using ABC techniques to determine costs from the perspective of the study. Resources were organized into cost categories (eg, personnel, patient care expenses, laboratory testing, equipment). Cost drivers were quantified, and unit cost per AE was calculated. A subset of time and motion studies was performed prospectively to observe clinic personnel time required for AE identification., Results: In 18 months, there were 9028 AEs, with 970 (11%) reported as serious adverse events. Unit cost per AE was $101.97. Overall, AE-related costs represented 32% ($920,581 of $2,834,692) of all study expenses. Personnel ($79.30) and patient care ($11.96) contributed the greatest proportion of component costs. Reported AEs were predominantly nonserious (mild or moderate severity) and unrelated to study drug(s) delivery., Conclusions: Intensive identification and management of AEs to conduct clinical trials ethically and protect human subjects require expenditure of substantial human and financial resources. Better understanding of these resource requirements should improve planning and funding of international HIV-related clinical trials.

Objectives: Use of single dose nevirapine (SD NVP) for prevention of HIV-1 mother-to-child transmission (pMTCT) is associated with selection of K103N-containing HIV variants. Repeat use of SD NVP for pMTCT may influence emergence and persistence of NVP-resistant variants., Design: K103N-containing variants were studied in 48 Ugandan women who received SD NVP in the HIVNET 012 trial, and were re-exposed to SD NVP in one (n = 44) or two (n = 4) subsequent pregnancies during a 5-year follow-up study., Methods: Samples were analyzed using the LigAmp assay (assay cutoff: 0.5% K103N)., Results: Among 44 women who were re-exposed to SD NVP in one subsequent pregnancy, 37.8% had K103N detected within 1 year of SD-NVP re-exposure. Detection of K103N was independently associated with detection of K103N 6-8 weeks after the first SD NVP exposure and with pre-NVP viral load. The portion of women with undetectable K103N by 2 years after SD NVP administration was similar after first versus second use of SD NVP for pMTCT. K103N was undetectable in 93.2% of evaluable women by 3 years of re-exposure. Only two of four women who received SD NVP in two pregnancies during the follow-up study had K103N detected after the last SD NVP exposure., Conclusions: K103N was detected in some women within 1 year of SD NVP re-exposure, but faded from detection in most women by 3 years after re-exposure. Detection of K103N by 1 year after SD NVP re-exposure was associated with prior selection of K103N-containing variants and with pre-NVP viral load.

In human immunodeficiency virus type 1 (HIV-1) subtype B, CXCR4 coreceptor use ranges from approximately 20% in early infection to approximately 50% in advanced disease. Coreceptor use by non-subtype B HIV is less well characterized. We studied coreceptor tropism of subtype A and D HIV-1 collected from 68 pregnant, antiretroviral drug-naive Ugandan women (HIVNET 012 trial). None of 33 subtype A or 10 A/D-recombinant viruses used the CXCR4 coreceptor. In contrast, nine (36%) of 25 subtype D viruses used both CXCR4 and CCR5 coreceptors. Clonal analyses of the nine subtype D samples with dual or mixed tropism revealed heterogeneous viral populations comprised of X4-, R5-, and dual-tropic HIV-1 variants. In five of the six samples with dual-tropic strains, V3 loop sequences of dual-tropic clones were identical to those of cocirculating R5-tropic clones, indicating the presence of CXCR4 tropism determinants outside of the V3 loop. These dual-tropic variants with R5-tropic-like V3 loops, which we designated "dual-R," use CCR5 much more efficiently than CXCR4, in contrast to dual-tropic clones with X4-tropic-like V3 loops ("dual-X"). These observations have implications for pathogenesis and treatment of subtype D-infected individuals, for the association between V3 sequence and coreceptor tropism phenotype, and for understanding potential mechanisms of evolution from exclusive CCR5 use to efficient CXCR4 use by subtype D HIV-1.

Background: An association has been demonstrated between herpes simplex type 2 (HSV-2) and HIV infection among men, but prospective studies in women have yielded mixed results., Objective: To estimate the effects of prevalent and incident HSV-2 infection on subsequent HIV acquisition among women in two African countries., Design: Prospective cohort study., Methods: HSV-2 and HIV serostatus were evaluated at enrollment and quarterly for 15-24 months among 4531 sexually active, HIV-uninfected women aged 18-35 years from Uganda and Zimbabwe. The association between prior HSV-2 infection and HIV acquisition was estimated using a marginal structural discrete survival model, adjusted for covariates., Results: HSV-2 seroprevalence at enrollment was 52% in Uganda and 53% in Zimbabwe; seroincidence during follow-up was 9.6 and 8.8/100 person-years in Uganda and Zimbabwe, respectively. In Uganda, the hazard ratio (HR) for HIV was 2.8 [95% confidence interval (CI), 1.5-5.3] among women with seroprevalent HSV-2 and 4.6 (95% CI, 1.6-13.1) among women with seroincident HSV-2, adjusted for confounding. In Zimbabwe, the HR for HIV was 4.4 (95% CI, 2.7-7.2) among women with seroprevalent HSV-2, and 8.6 (95% CI, 4.3-17.1) among women with seroincident HSV-2, adjusted for confounding. The population attributable risk percent for HIV due to prevalent and incident HSV-2 infection was 42% in Uganda and 65% in Zimbabwe., Conclusions: HSV-2 plays an important role in the acquisition of HIV among women. Efforts to implement known HSV-2 control measures, as well as identify additional measures to control HSV-2, are urgently needed to curb the spread of HIV.

K103N is frequently detected in HIV-infected women after single dose (SD) nevirapine (NVP). K103N-containing variants were detected more frequently by the ViroSeq HIV-1 Genotyping System in women with subtype C (69.2%) than subtypes A (19.4%, p < 0.0001) or D (36.1%, p < 0.0001). K103N-containing variants were also detected more frequently and at higher levels in women with subtype C by the LigAmp assay. In this report, we analyzed samples collected prior to or within hours after SD NVP administration from antiretroviral drug-naive African women with subtypes A, C, and D. Only 1/254 samples had an NVP resistance mutation detected with the ViroSeq system, and only 4/236 samples had K103N detected at < 0.5% with the LigAmp assay [2/110 (1.8%) with subtype A, 1/46 (2.2%) with subtype C, and 1/80 (1.3%) with subtype D] (p = 0.92). We did not detect significant differences in the pre-NVP frequency of NVP resistance mutations or the pre-NVP levels of K103N-containing variants in women with subtypes A, C, and D that explain the dramatic subtype-based differences in emergence of HIV-1 variants with these mutations after SD NVP exposure.

K103N-containing human immunodeficiency virus (HIV)-1 variants are selected in some women who receive single-dose (SD) nevirapine (NVP) for prevention of HIV-1 mother-infant transmission. We examined the persistence of K103N in women who received SD NVP prophylaxis. K103N was detected using the LigAmp assay (assay cutoff, 0.5% K103N). K103N was detected at 6-8 weeks in 60 (41.7%) of 144 women. Fading (lack of detection) of K103N was documented in 16 women by 2 years, 43 women by 3 years, and 55 women by 4 and 5 years. Slower fading was independently associated with HIV-1 subtype (D>A) and higher pre-NVP viral load.

Background: Combined oral contraceptives (COC) and depot-medroxyprogesterone acetate (DMPA) are among the most widely used family planning methods; their effect on HIV acquisition is not known., Objective: To evaluate the effect of COC and DMPA on HIV acquisition and any modifying effects of other sexually transmitted infections., Methods: This multicenter prospective cohort study enroled 6109 HIV-uninfected women, aged 18-35 years, from family planning clinics in Uganda, Zimbabwe and Thailand. Participants received HIV testing quarterly for 15-24 months. The risk of HIV acquisition with different contraceptive methods was assessed (excluding Thailand, where there were few HIV cases)., Results: HIV infection occurred in 213 African participants (2.8/100 woman-years). Use of neither COC [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.69-1.42] nor DMPA (HR, 1.25; 95% CI, 0.89-1.78) was associated with risk of HIV acquisition overall, including among participants with cervical or vaginal infections. While absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 (HSV-2) than in those seronegative at enrolment, among the HSV-2-seronegative participants, both COC (HR, 2.85; 95% CI, 1.39-5.82) and DMPA (HR, 3.97; 95% CI, 1.98-8.00) users had an increased risk of HIV acquisition compared with the non-hormonal group., Conclusions: No association was found between hormonal contraceptive use and HIV acquisition overall. This is reassuring for women needing effective contraception in settings of high HIV prevalence. However, hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition. Additional research is needed to confirm and explain this finding.

Introduction: We used a sensitive point mutation assay, LigAmp, to detect and quantify K103N-containing variants in African women who received single-dose nevirapine (NVP) to prevent mother-to-child HIV-1 transmission., Methods: Plasma for testing was collected 6 to 8 weeks postpartum from 301 women (144 subtype A, 63 subtype C, and 94 subtype D)., Results: The portion of women with 0.5% or more K103N-containing variants was lowest for subtype A (60/144, 41.7%) and highest for subtype C (44/63, 69.8%; P < 0.0001). K103N was rarely detected in pre-NVP samples. In a multivariate model, K103N detection was associated with HIV-1 subtype (C > A), after adjusting for log10 delivery viral load, the number of days between NVP dosing and sample collection, age, and parity. Among women with K103N detected: (1) the median %K103N was lower for subtype A (2.2%) than C (11.7%, P = 0.0001) or D (5.5%, P = 0.04), and (2) in a multivariate linear model, higher log10 (%K103N) was associated with HIV subtype (C > A, P = 0.0001; D > A, P = 0.01; and C vs D, no difference), but not other factors., Conclusions: After administration of single-dose NVP, K103N was detected more frequently and at higher levels in women with subtypes C and D than A. Further studies are needed to evaluate the clinical significance of NVP-resistant variants in this setting.

Background: To correlate nevirapine presence and concentration in cord bloods of infants born to HIV-1 infected women with report of timing of dose and HIV-1 transmission at 6 weeks of age., Methods: All available cord blood samples from the infants of mothers enrolled in the HIVNET 012 trial who were randomly assigned to receive either nevirapine or zidovudine at the onset of labor were tested for a nevirapine concentration., Results: Nevirapine was detected in the cord blood of 244 of 259 (94%) infants whose mothers reported they took nevirapine in labor more than 1 h before delivery and in 12 of 13 (92%) infants whose mothers reported they took nevirapine less than 1 h before delivery. The median nevirapine cord blood concentration was 1238 ng/ml [interquartile range (IQR), 905-1474 ng/ml] and 122 ng/ml (IQR, 64-321 ng/ml) for women who reported taking nevirapine more or less than 1 h before delivery, respectively (P < 0.001). The median nevirapine cord blood concentration of infants who were HIV-1 negative at birth, but positive at 6-8 weeks of age (n = 11), was 916 ng/ml (IQR, 737-1245 ng/ml) compared with 1192 ng/ml (IQR, 875-1471 ng/ml) for uninfected infants (n = 236)., Conclusions: Cord blood nevirapine concentration correlated well with report of nevirapine administration and timing of dose before delivery. The nevirapine cord blood concentration was modestly lower in infected infants, although the number of infants infected between birth and 6-8 weeks of age was small (n = 11). The high adherence rate in the HIVNET 012 study supports the efficacy, simplicity and deliverability of this regimen.